Direct action of estradiol-17β on the atrial action potential

The effect of the two C-17 isomers of estradiol on the shape of the action potential of rat atrial tissue was studied by means of classical glass electrodes for different concentrations of estradiol. Resting potential and upstroke were not affected by estradiol, but the duration of the action potential was reduced. Only estradiol-17β exhibits an effect in a concentration dependent way, while estradiol-17α has no effect at all. The ionic mechanism was studied by adding specific ionic blockers to the perfusate. Since the effect was much less pronounced when a slow inward current blocker was added, it was concluded that estradiol-17β acts mainly via the slow inward current channel. Only a small part of the interaction takes place via the potassium outward channel.     

On the action of sulfanilamide

Summary A. According toMellon,Locke andShinn, the bacteriostatic action of sulfanilamide is due to the inactivation of (bacterial) catalase and the resulting accumulation of hydrogen peroxide. The probability of this theory is discussed. B. Catalase activity was studied by means ofPhotobacterium Fischeri, as an oxygen indicator. By adding hydrogen peroxide to the tested cultures of bacteria it has been demonstrated, that: I.Bacterium coli, Photobacterium Fischeri andStreptococcus haemolyticus (strainAronson) contain catalase. II. Sulfanilamide does not inactivate the catalase in blood. III. Sulfanilamide does not inactivate bacterial catalase nor does it affect the production of catalase in the growing culture containing the drug. So we have to conclude that the assumption of catalase inactivation to be the essential factor in sulfanilamide action on bacteria will not lead us to the solution of the problem. First communication:L. K. Wolff andH. W. Julius, Ann. de l'Inst. Pasteur62, 616, 1939.     

On the action of sulfanilamide

Summary Studying the action of sulfanilamide on bacterial nitrogen metabolism, it was shown that: a. Sulfanilamide does not alter the rate of gelatin-hydrolysis by papain or by the proteinase ofB. pyocyaneum andB. prodigiosum. b. Sulfanilamide does not influence the synthesis of aspartic acid from fumaric acid and ammonium chloride by restingB. coli. c. Addition of single amino acids does not counteract sulfanilamide. d. Addition of single amino acids merely accelerates growth slightly; a marked acceleration was obtained only by adding various amino acids simultaneously. e. The addition of such an optimal mixture of amino acids did not exert any influence on the action of sulfanilamide on growth. As the growth acceleration shows that the bacteria are saved an important output of energy in synthesis as a result of the supply of the amino acids, we conclude that sulfanilamide action cannot be due to interference with the synthesis of amino acids from inorganic nitrogen (f.i. NH₂ + pyruvate).Considering these facts, we expect sulfanilamide to pursuit its action on bacterial growth by interfering with protein anabolism, anywhere in the synthesis of protein from amino acids.     

Nonlever action of the mandible

This study considers the current concept of the mandible as a lever of the third order. The concept requires a fulcrum, and this function has been ascribed to the condyle region, but it tends to be overlooked that the fulcrum of a third-order lever in this case would sometimes have to bear a considerable stress. Certain changes, attributed to stress, have been observed in anatomical components of the articulation, but they cannot be explained in terms of the lever concept. They are accounted for by the changing anatomical relations in the working and contralateral sides during mandibular function. They arise from minor stress, especially when dental conditions indicate a period of abnormal function.     

On the action of sulfanilamide

Summary InE. coli, sulfanilic acid, sulfanilamide, sulfapyridine, sulfapyrimidine and sulfathiazol are antagonized by the same series of non competitive antagonists,viz., methionine, xanthine, serine, thymine and valine. This seems to indicate that the biosynthesis of these substances is successively inhibited by increasing concentrations of these sulfadrugs; the synthesis of methionine being inhibited first, that of valine only by excessive concentrations. Though the absolute concentrations vary with the drug the relative sensitivity of the five enzyme systems are very much the same. This again shows that the intrinsic toxicity of the sulfadrugs is the same.I: Ann. de l'Inst. Pasteur62, 616, 1939. II: Antonie van Leeuwenhoek7, 25, 1941. III: Ibid.7, 77, 1941. IV: Ibid7, 153, 1941. V: Ibid.7, 161, 1941. VI: Ibid.8, 10, 1942. VII: Ibid.8, 86, 1942. VIII: Ibid.8, 139, 1942. IX: Ibid.9, 115, 1943. X: Ibid.10, 1, 1944–1945. XI: Arch. of Biochemistry18. 97, 1948.     

On the action of sulfanilamide

Summary Methionine, xanthine and thymine replace para-aminobenzoic acid as a growth factor for the para-aminobenzoic-lessE.coli mutant strain 273.The same substances were able to antagonize non competitively the bacteriostatical activity of 2000 mg/l sulfanilamide completely. It was further shown that the observed differences in sensitivity of the reaction chains leading to methionine, xanthine and thymine are not due to a difference in sensitivity to sulfanilamide but a difference in sensitivity to para-aminobenzoic acid. This seems to indicate that there exists only one reaction which is inhibited by sulfanilamide.XIII: Antonie van Leeuwenhoek15, 136, 1949.     

On the action of sulfanilamide

Summary The better activity (in vitro) of various sulfanilamide compounds as compared with sulfanilamide itself is only quantitative,i.e., an equal activity is obtained with lower concentrations. It is shown, that the activity of the studied drugs is so narrowly related to their adsorption in the bacteria (B. coli), that probably the varying activity of the studied compounds is due to differences in adsorbability. For different drugs the adsorbed amount was equal for concentrations with equal activity.The concentration of p. aminobenzoic acid which re-establishes growth — in cultures containing the studied compounds in concentrations of equal activity — was equal in all cases. This fact corroborates the hypothesis, that activity and adsorption are correlated and shows, that the mechanism of action (in vitro) is the same in all cases.Ninth communication: K. C.Winkler, Antonie van Leeuwenhoek9, 115, 1943.     

On the action of sulfanilamide

Summary A sulfanilamide activating principle was found to be present in red cells of the horse. This activator substance is active in the rather high dilution of 0.5% haemolysed red cells.The substance or substances are present in the red cells, not in their cell membranes. They seem to be of a protein nature or adsorbed to the protein (haemoglobin).In some media no sulfanilamide action is obtained without the activator. In other media sulfanilamide action, though clearly present, is markedly enhanced. So it must be emphasized, that the substance under discussion is an activator and not a conditio sine qua non for the sulfanilamide action and its characteristics.The substance is activating sulfanilamide against streptococci, staphylococci andB. coli.The substance is not present in human blood or in the red cells of sheep, rabbits or mice.Sixth communication: K. C.Winkler, Antonie van Leeuwenhoek8, 10, 1942.     

Bio-agency and the problem of action

The Aristotle-Kant tradition requires that autonomous activity must originate within the self and points toward a new type of causation (different from natural efficient causation) associated with teleology. Notoriously, it has so far proven impossible to uncover a workable model of causation satisfying these requirements without an increasingly unsatisfying appeal to extra-physical elements tailor-made for the purpose. In this paper we first provide the essential reason why the standard linear model of efficient causation cannot support the required model of agency: its causal thread model of efficient causation cannot support the core requirement that an action is determined by, and thus an expression of, the agent’s nature. We then provide a model that corrects these deficiencies, constructed naturalistically from within contemporary biology, and argue that it provides an appropriate foundation for all the features of genuine agency. Further, we provide general characterisations of freedom and reason suitable to this bio-context (but that also capture the core classical conceptions) and show how this model reconciles them.

Detubulation effects on the action of zinc on frog skeletal muscle action potential

Summary Detubulation of the untreated fiber decreases the time constant of the action potential's foot ( _f ) and increases the maximal rate of rise of the spike ( ). Zinc at all concentrations, and regardless of whether the fiber is intact or detubulated, increases _f and decreases , and thus seems to decrease Na activation of the fiber. Detubulation was used principally to elucidate the localization and mechanism of the Zn²⁺-induced retardation of the falling phase of the frog sartorius fiber action potential, which evidently results from a general depression of delayed rectification. At 50 to 1000 m, Zn²⁺ not only prolongs repolarization of intact fibers (measured by increase int _0.5, the half-time of the spike's fall), but also produces a marked hump early in this phase. Detubulation of zinc-free fibers reducest _0.5 to about 80% of its intact value, and under Zn²⁺ treatmentt _0.5 is increased but only to about 80% of that produced in the intact fiber, and the falling-phase hump is completely obliterated. Thus, detubulation decreasest _0.5 in Zn²⁺-treated fibers not only by generally eliminating T-tubular participation in action potential generation, but also by subtracting a Zn²⁺-induced retardation of tubular delayed rectification. Tubular delayed rectification must therefore be an intrinsic feature of normal excitation. These results are further analyzed by means of (i) Stanfield's findings about retardation of delayed rectification by Zn²⁺ and (ii) Adrian-Peachey's theory of T-tubule participation in action potential generation, which suggests that the Zn²⁺-evoked repolarization hump signals onset of Zn²⁺-altered active participation of T-tubules in determining the spike's shape.Died April 17, 1978. Previously known as: P.M.K. Dass, and so listed in the reference Dass and Sandow (1972).