Inhibiting effect of (sarcosine-1-isoleucine-8)-angiotensin II in anesthesized rats

The peptidic sequence (Sarcosine-1-Isoleucine-8)-Angiotensin II has been demonstrated to be an in vitro specific and competitive antagonist of the Angiotensin II action. The present results show it to be a competitive antagonist also in vivo since pA2 values are similar, always reaches a 100% response on increasing the Angiotensin II dose, and when relating log (DR-1) and log dose of agonist, the slope is very near to one (0.925).     

Induction of the blue form of bacteriohodopsin by low concentrations of sodium dodecyl sulfate

The effects produced on bacteriorhodopsin by low concentrations of several detergents have been studied by absorption and fourth-derivative spectrophotometry. Sodium dodecyl sulfate induces the appearance of the blue form of bacteriorhodopsin (λ_max = 600 nm) at pH values up to 7.0 in a reversible manner. The apparent pK of the purple-to-blue transition raised with increasing concentration of SDS. Of the other detergents tested, only sodium dodecyl-N-sarcosinate showed a slight red-shift of the absorption band to 580 nm, whereas sodium taurocholate, Triton X-100 and cetyltrimethylammonium bromide did not favour the appearance of the blue form. The effect of SDS was found to be consistent with a localized conformational change that moves away the counter-ion of the protonated Schiff base.     

Iminoglycinuria in a child in Czechoslovakia

Summary The child with iminoglycinuria is in our observation. Hyperprolinuria was seen at 5 months by screening program. The child was repeatedly examined in the hospital and was seen last time at 16 months. IQ was 67, in the urine were excessive amounts of glycine, proline a hydroxyproline. In the blood aminoacids were in normal levels. In the child was noticed the same increase of proline in the blood as in the control child of the same age following loading test with L-proline, indicating normal intestinal absoption. Both parents and father's sister's 2-year-old mentally retarded child exhibit excessive glycinuria. The father, his sister, father's father, and grandfather are partialy, congenitaly deaf.     

Thermal melting and circular dichroism of DNA complexes with (Lys-Ala-Ala)10 and (Lys-Ala-Ala)n: effect of polypeptide chain length

DNA complexes with polypeptides (Lys-Ala-Ala)₁)] and (Lys-Ala-Ala)₃₄ have been studied using the methods of thermal melting and circular dichroism. Derivative melting curves of (Lys-Ala-Ala)₁₀ DNA differed substantially from those of (Lys-Ala-Ala)₃₄ prepared either by salt gradient dialysis or by direct mixing. Melting curves of the former complex were unimodal or bimodal with T_m increasing continuously withn input lysin-to-DNA phosphate ratio (r); those of the latter complex consisted of three separate transitions with T_m values almost independent of r. Complete reversibility of binding in the (Lys-Ala-Ala)₁₀-DNA system but a slow redistribution of (Lys-Ala-Ala)₃₄ on DNA at low temperature were found in the redistribution experiments Much faster redistribution from denatured to native DNA occurs at the temperature of melting, contributing to the unusual trimodal melting pattern. Circular dichroism curves are very similar for both complexes and indicate little change of DNA conformation upon polypeptide binding.     

Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition

Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration.     

The effect of carbofuran-toxication on the chloragogen tissue of Tubifex tubifex Müll. (Oligochaeta).

Chloragogen cells, subserving ion exchange and electron accepting functions, were studied in Tubifex tubifex after insecticide treatment. Chloragogen cells were strongly influenced by in vivo carbofuran poisoning. The first alterations in the chloragogen cells became activated, both the formation and release of the chloragosomes reached a high rate. The released chloragosomes were phagocytosed by the amoebocytes. At an advanced stage of the toxication a heavy loading of the apical cytoplasm of chloragogen cells with lipid droplets, finally degenerative changes both in the chloragogen cells and amoebocytes were observed. Possible mechanisms of the carbofuran toxication and of the protective function of chloragogen cells in T. tubifex are discussed.