Fluid and Protein Secretion by the Submandibular Glands of Weanling Rats in Response to Cholinergic and Peptidergic Agonists at Various Doses

Fluid and protein secretion by the submandibular glands of 25-day-old rats were examined and compared in response to three cholinergic and four peptidergic sialogogues at various doses. All cholinergic and peptidergic agonists used were potent sialogogues for the submandibular glands of the weanling rats over the wide range of doses used. The cholinergic agonists, bethanechol and methacholine and the peptidergic agonists, substance P, substance P^Tyr8 and eledoisin-related peptide used intravenously, acted similarly to each other on the submandibular glands of the rats, late in the natural weaning period, but carbachol and physalaemin had slightly different effects. Of the peptidergic agonists, physalaemin was the most potent sialogogue among four tachykinins tested at the low dose. The types of protein secreted by the submandibular glands of the weanling rats in response to all sialogogues used here were typical of the β-type. These results indicate that all agonists used could mainly stimulate the acinar cells of the submandibular glands of the weanling rats which have already fully developed functionally at this time.     

Quantitative structure–activity relationship (QSAR) study of elastase substrates and inhibitors

One hundred Suc-X-Y-Ala-pNA peptides (SUC: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, x-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (K_m, K_cat and K_cat/K_m) were determined. These reaction constants were quantitatively analyzed using the Free–Wilson/Fujita–Ban method. The contribution of amino acid side chains to the reaction constants K_m, K_cat and K_cat/K_m), expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF₃CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the K_i value of the inhibitor was generally correlated to the K_m value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation This study may serve as a prototypical approach to unraveling structure–activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance.     

Ultrathin films of charged polysaccharides assembled alternately with linear polyions

As a means of preparation of biocompatible molecular surfaces, an alternate assembly of charged polysaccharides and oppositely-charged synthetic polymers was conducted. Cationic chitosan was assembled alternately with anionic poly(sodium styrenesulfonate) (PSS) at pH 4. Regular film growth and its dependence on ionic strength were detected by the quartz crystal microbalance (QCM) method. Averaged film thicknesses for the chitosanCPSS layer were 15, 31, 46, and 69 A° , respectively, when 0, 0.25, 0.5, and 1 M of NaCl was contained in aqueous chitosan. Adsorption of chitosan did not reach saturation in 20 min at 0 M NaCl, while the adsorption became saturated within 6 min with 0.25 M NaCl. Anionic sodium chondroitin sulfate was also assembled in alternation with cationic poly(dimethyldiallylammonium chloride) (PDDA) at pH 6.5. The adsorption of chondroitin sulfate was less sensitive to ionic strength. Surface morphology of chitosan–PSS films was investigated by non-contact atomic force microscopy (AFM) observation. Maximum height difference and Ra value for a 1000 × 1000 nm area were 11 and 0.69 nm, respectively, indicating the formation of a molecularly flat surface by alternate layer-by-layer adsorption.     

New Diagnostic Finding to Assess Para-Hisian Pacing Observed in a Patient with a Permanent Form of Junctional Reciprocating Tachycardia

Morphologic Change During Para-Hisian Pacing. Para-Hisian pacing, a useful method to differentiate conduction over an accessory pathway from conduction over the AV node, is assessed essentially by comparing the timing of local atrial electrograms between Hisbundle captured heats and His-bundle noncaptured heats. We describe the case of a patient with a permanent form of junctional reciprocating tachycardia, in whom an atrial double potential was recorded only during the tachycardia at the right posterior septum. During para-Hisian pacing, a morphologic change in the atrial electrogram at the posterior septum was also identified, as well as a change in the retrograde atrial sequence. Since the morphologic change of atrial electrograms during para-Hisian pacing cannot be demonstrated in a patient without an accessory pathway, this new finding could he considered a new additional diagnostic criterion suggesting the presence of an accessory pathway.     

Inhibitory Effects of Daunorubicin on Endothelium-dependent Vasorelaxing Response to Acetylcholine of Rat Aorta

Abstract— The effect of daunorubicin on the endothelium-dependent vasorelaxing response to acetylcholine was investigated using rat isolated aorta and compared with the effect of aclarubicin. Treatment of aortic strips with daunorubicin (20 μM) significantly attenuated the relaxing response to acetylcholine in the absence of tetraethylammonium, but not in its presence. Pretreatment with daunorubicin at a higher concentration (50 μM) or with aclarubicin (20 μM) strongly attenuated the relaxing response to acetylcholine; this attenuation was unaffected by the presence of tetraethylammonium. The increase in aortic cGMP in response to acetylcholine was also significantly suppressed by pretreatment with 50 μM daunorubicin or 20 μM aclarubicin, but not by treatment with 20 μM daunorubicin. The inhibitory effect of 20 μM aclarubicin on the acetylcholine-induced responses was stronger than that of 50 μM daunorubicin. Even in strips pretreated with both 50 μM daunorubicin and 20 μM aclarubicin, relaxation induced by 0·1 μM sodium nitroprusside was retained. These results suggest that daunorubicin at 20 μM inhibits the endothelium-dependent vasorelaxing response to acetylcholine via a mechanism other than the nitric oxide-mediated pathway, whilst at 50 μM, it inhibits the nitric oxide-mediated vasorelaxation.     

Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis

Abstract We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vascodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease.