Initial Rapid Fall Research Articles

Uptake and disappearance of 1α- 3H-chlormadinone acetate in various tissues of the rat

The uptake and disappearance of 1 α- 3H-chlormadinone acetate (CAP) in various tissues of the rat have been studied after a single injection and a constant infusion. CAP is rapidly taken up by the neural and genital tissues. The disappearance curve showed an initial rapid fall followed by a slow disappearance: The slow disappearance part of the curve indicates some retention of the CAP and its metabolites in these tissues. The molar concentration of the steroid and its metabolites in the uterus and ovary was 2.4 × 10 −7M and 6.6 × 10 −7M, respectively, after a constant infusion for five hours. The uptake in the ovary was higher than that in the uterus indicating the possibility of direct action of CAP on the ovary. Compared with neural and genital tissues, mammary gland and fat showed a much higher uptake of CAP. The molar concentration of CAP in the mammary gland was 3.9 × 10 −6M at 120 minutes, and there was evidence of retention of CAP in the mammary gland. The significance of these findings in the action of CAP is discussed.

The assimilation and chronic effects of sub-lethal concentrations of Endosulfan on condition and spawning in the common mussel Mytilus edulis

The rate of uptake of Endosulfan by Mytilus edulis L. exposed to pesticide concentrations of 0.1, 0.5, and 1.0 mg/l, and its subsequent elution on removal to clean sea water, was investigated. Higher residue levels were recorded for mussels exposed to higher concentrations of the pesticide, but concentration factors were reduced. There was a rapid initial fall in tissue residue levels on transfer to clean sea water due, it is suggested, to elution of Endosulfan adsorbed on particulate matter assimilated in the gut. The spawning period was prolonged at higher concentrations and, at 1.0 mg/l, the onset of spawning was delayed, possibly due to interference with gamonic action. At 0.1 mg/l, the minor protraction of the spawning period may reflect the effect of experimental tank conditions. No seasonal trend was obvious, and there was an exaggeration of the expected fall in condition in mussels exposed to higher concentrations of Endosulfan. In controls, the expected seasonal trend was reduced.

The carotid body in the duck and the consequences of its denervation upon the cardiac responses to immersion.

1. The anatomy of the carotid body and its afferent nerve supply was studied in the duck and a method of denervating the carotid body which ensures a satisfactory post-operative course is described.2. The effect of denervating the carotid body upon the cardiac response to immersion of the head in water was studied in ten ducks which at the time of the test were unanaesthetized.3. When the nerves were intact, immersion of the head caused a fall in heart rate after a latent period of between 1 and 9 sec to an average of 24% of the resting rate after 30 sec. Simultaneous measurement of arterial oxygen tension (P(a, O2)) in the brachiocephalic artery showed a rapid initial fall during the initial 10 sec from control levels, 93-103 mm Hg, to between 42 and 47 mm Hg, followed by a gradual fall of 3-5 mm Hg for each subsequent 30 sec period of submergence.4. Following carotid body denervation, the latent period before heart rate started to fall was no different from control but the average fall in heart rate was now to 90% of the resting rate and brachiocephalic P(a. O2) continued to fall steadily during submergence reaching levels of between 10 and 21 mm Hg by the end of the second minute.5. Stimulation of the central end of branches of the IXth (glossopharyngeal) nerve supplying the glottis caused apnoea and bradycardia.6. It is concluded that apnoea and bradycardia during submergence in the duck is initiated reflexly from receptors in the nares, pharynx and glottis but that the profound degree of bradycardia and mechanisms which maintain a relatively high P(a, O2) are regulated by peripheral chemoreceptor activity.

Osmotic factors determining the release of catecholamines from isolated chromaffin cell granules.

AbstractLishajko, F. Osmotic factors determining the releme of catecholamines from isolated chromaffin cell granules. Acta physiol. scand. 1970. 79. 64–75.On incubation of bovine adrenal medullary granules in isotonic sucrose, KCl, NaCl or K‐phosphate, noradrenaline (NA) is initially released at a rapid rate followed by a slow exponential release. Adrenaline (A) release in the same media does not show the rapid initial phase. In hypotonic media both NA and A show a rapid initial release while in hyper‐tonic solutions both NA and A are released at a constant slow rate (t/2 = 115–185 min at 37°). Partial replacement of sucrose or dextrose media by NaCI, KCl or K‐phosphate decreases the release rate of Na and A. Addition of 6 mM Mg2+ or Ca2+ prevents the initial rapid fall of NA and of A in hypotonic solution. ATP‐Mg2+ inhibits the release rate of catecholamines in chloride free media more than ATP or Mg2+ alone. The granules were shown to shrink in the presence of divalent ions, as well as on addition of ATP or ATP‐Mg2+. During partial lysis or “osmotic shock” the granules lose slightly more A than NA. The results suggest that the NA containing granules from chromaffin cells initially possess a higher osmotic pressure than that of the A granules, possibly depending on the rate of splitting of an amine‐ATP‐complex. The release may depend partly on the ensuing osmotic equilibration process.

Reaction of CO2 with Human Hemoglobin Solution

Abstract We have measured the disappearance of dissolved CO2 with time after the mixing of dialyzed human hemoglobin solution (average 7.76 mm) at a CO2 partial pressure of nearly zero and water equilibrated with 75 torr of CO2 in a continuous flow rapid reaction apparatus with the use of a CO2 electrode to indicate its partial pressure. po2 was zero in both solutions and the temperature was 37°. Acetazolamide (1.1 mm) was included to inhibit carbonic anhydrase. There was (a) a rapid initial fall in pco2, complete within approximately 0.1 sec and (b) a further slow fall continuing out to several seconds. The initial fall (Process a) is greater at greater pH and less when the hemoglobin is oxygenated. The decrement in pco2 at 0.1 sec corresponds to the formation of amounts of hemoglobin carbamate equal to those reported by others with different techniques, within experimental error. We conclude that Process a represents the formation of hemoglobin carbamate and Process b represents the uncatalyzed hydration of CO2. The velocity constant for the reaction of CO2 and hemoglobin-NH2 (ka) was estimated from the relation between the over-all velocity of the reaction and [H+], which gives a value of 11,000 m-1 sec-1. This value of ka is dependent upon the value chosen for the equilibrium constant (Kz) of the pertinent hemoglobin NH2 groups with H+ ions, which was considered to approximate 7.2 x 10-8 m. The equilibrium constant for the reaction of CO2 and hemoglobin-NH2, Kc, was calculated with less reliability from the change in pco2 at 0.1 sec, under the assumption that it represented equilibrium of carbamate and CO2. Values ranged from 2 x 10-5 to 8 x 10-6, as compared with an estimate of 2.4 x 10-5 in the literature. When this last value is assumed for Kc, and a minimal value for the acid ionization constant of hemoglobin-NHCOOH is taken as 10-6 m, the velocity constant for the dissociation, kd, approximates 500 sec-1. Calculations from previously reported measurements of the rate of CO2 uptake by suspensions of deoxygenated human red cells give a ka within the cell of approximately 5 x 103 m-1 sec-1, which is probably not significantly different from that in solution.

Ionic Interaction with Bone Mineral. III. Reversible Calcium Exchange with Bone Powder

The curve describing the uptake of 45Ca by bone powder or by synthetic hydroxyapatite shows an initial rapid fall in radioactivity of solution followed by a mono-exponential decline at a slower rate. Wash-out experiments were performed on the labelled crystals before and during the period of mono-exponential fall by resuspending the crystals, collected by filtration, in medium free of isotope. More than 80% of radiocalcium could be removed from the crystal phase by this procedure regardless of the period of labelling. Results from published reports are interpreted to show that “back-diffusion” of isotope from bone into solution is operative only at a certain region of the uptake curve; our studies contradict this interpretation.

Isolation of three different neurotoxins from indian cobra ( Naja naja) venom and the relation of their action to phospholipase a

Six fractions of the venom of the Indian cobra (Naja naja) were separated by paper electrophoresis of which four (fractions 6, 3, 2 and 1) were toxic in anaesthetized cats or in mice, or in both species. Of the four toxic fractions only fraction 6 contained phospholipase ; it was toxic to cats but not to mice. Fraction 3 was toxic to cats and mice and fractions 1 and 2 were toxic to mice but not to cats. Thus three different neurotoxic fractions were separated. In the anaesthetized cat the intravenous injection of fraction 6 caused the same effect as the injection of whole or boiled venom, i.e., a diphasic circulatory shock—an initial rapid fall in arterial blood pressure followed after partial recovery by a delayed gradual fall—with depression of cerebral cortical activity. The central vasoregulating mechanisms were apparently not affected during the shock since records taken from the cervical sympathetic showed increased activity. Fraction 3 did not produce the initial fall in arterial blood pressure but only the delayed phase of shock. In mice, the toxic effects of an intraperitoneal injection of whole venom resulted in convulsions, excitement, motor impairment and respiratory arrest; the injection of fractions 1 and 2 resulted in apathy, motor depression and convulsions before death, and the injection of fraction 3 in excitement, convulsions, repeated laboured respiration, and curling of the tail.

Metal ion and energy requirements in the triamcinolone-induced swelling of mitochondria

The effect of triamcinolone on rat liver mitochondrial swelling has been studied by measuring changes in the optical density at 520 mμ. The action of the steroid is characterized by a rapid initial fall in the optical density which is strictly dependent on the cationic environment; the order of effectiveness of the metal ions is: Li + < Na + < K + = Rb +. The triamcinolone-induced swelling phenomenon takes place in hypertonic solutions, is more marked at high pH, and is diminished by the presence of ammonium in the incubation mixture. Indirect evidence indicates that it is the metal ion which produces the structural change after the steroid has bound to the mitochondria. For a maximum rate of the triamcinolone-induced swelling, high-energy intermediates of oxidative phosphorylation seem to be required. Triamcinolone-swollen mitochondria show a rise in the optical density after the addition of adenosine triphosphate, guanosine triphosphate, inosine triphosphate and heparin, but only if the incubation mixture is at pH 4.0.

A possible correlation between ATPase activity and Na content of embryonic chick heart.

The water content of embryonic chick ventricles decreases gradually from 88% at 2 days of incubation to 83% shortly after hatching. Ventricular protein nitrogen decreases during early development and then increases rapidly at midfetal age until hatching, after which a more gradual increase continues. Magnesium-activated ATPase activity of whole ventricle homogenates at pH 7.0–7.5 is much greater than is the calcium-activated enzyme throughout development. A very marked increase in Mg-ATPase occurs between 4 and 7 days of incubation; a lesser increase occurs just prior to and after hatching. Calcium-ATPase increases gradually throughout development. Magnesium-ATPase has been identified with both isolated mitochondrial and microsomal fractions; Ca-ATPase is exclusively associated with the myosin fraction. Myokinase occurs in the supernatant. Optimal pH's are given for the enzymes. It is suggested that the initial rapid fall in ventricular Na content between 2 and 7 days of incubation is directly related to two events: disappearance of the cardiac jelly and establishment of an effective Na extrusion mechanism.

Anisindione: A new anticoagulant with unusual properties

1. 1. Anisindione (2-p-Anisyl indandione—1, 3) is an anticoagulant of the indandione type. It was given to 52 patients with vascular disease, but not always the thromboembolic type, for a total of 1,198 days. It leads to an initial rapid fall in prothrombin activity and reaches a therapeutic level within 36 to 72 hours. 2. 2. The therapeutic level can be maintained rather uniformly by 1 dose of the drug every third day. 3. 3. The individual response to a given dose of the drug is unusually uniform. 4. 4. The effect of the drug can be rapidly interrupted by the use of phytonadione (Mephyton). The anticoagulant effect can be restored rapidly by remedication. 5. 5. Maintenance doses of the drug retain the anticoagulant effect previously established with Dicumarol. 6. 6. Side reactions were noticeably absent in this group. There were 3 instances of hematuria, 1 occurring at a therapeutically desirable level, 1 in a case with a renal calculus, and 1 at a purposely induced very low prothrombin activity. There was no chromaturia, petechiae, agranulocytosis or liver damage.

AN APPARATUS FOR TESTING AND COMPARING THE BIOLOGICAL ACTION OF INSECTICIDES ON FLYING INSECTS AND A METHOD FOR SAMPLING THE CONCENTRATION OF THE ATOMIZED INSECTICIDE

Summary An apparatus and method for testing the effect of atomized sprays on flies and mosquitoes are described. The apparatus consists of a revolving wire gauze cage placed in a thermostatically controlled chamber, the whole of which may be easily cleaned and freed from toxic residues. The insecticide is sprayed into the chamber by means of an Aerograph MP gun and distributed by means of a slow‐moving fan. When the insecticide has been injected and an interval allowed for the initial rapid fall of concentration, the movement of the cage is stopped and the insects are introduced into it by means of a special tube and plunger. The time required for paralysis to take place is recorded. After a given interval the insects are removed from the gauze cage and kept to ascertain the mortality. A technique for sampling the concentration of insecticide in the air space is described. The insecticide carrier is coloured with a dye, Sudan III for petroleum oil bases and methylene blue for water bases. The percentage of atomized material remaining in the atmosphere at any given time is determined by aspirating a known quantity of the atmosphere of the chamber through a sintered glass filter. The dye is retained in the filter, it is washed out with a measured quantity of liquid and compared with known standards. Reasons are given for the assumption that the dye molecules will behave in the same way as the insecticide molecules.This sampling method has been used to study the behaviour of a light oil, a heavy white oil and water at different degrees of atomization. Tables and graphs are given which show that, except with a fine atomization where most of the insecticide remains suspended for a considerable time, there is an initial rapid fall, which varies in amount with the degree of atomization. This initial fall is followed by a much more gradual decrease of concentration. The experiments show clearly that oil bases of different physical properties cannot be compared adequately unless a sampling method is used to ascertain the quantities of material remaining suspended. Where water bases are used it is shown that the time concentration curve varies not only with the degree of atomization, but also with the degree of saturation of the atmosphere before spraying. The concentration remains higher in an unsaturated atmosphere than in a saturated one.

NUTRITIONAL EDEMA IN THE DOG

1. The concentration of protein in the serum and plasma of normal dogs is given. Analyses of serum from 38 animals yielded the following averages and standard deviations, (a) for albumin: 3.26 +/- 0.48 gm. per cent, (b) for globulin: 2.72 +/- 0.76 gm. per cent, and (c) for total protein: 5.98 +/- 0.67 gm. per cent. Analyses of plasma from 19 animals showed, (a) for albumin: 3.38 +/- 0.38 gm. per cent, (b) for globulin: 2.98 +/- 0.55 gm. per cent, and (c) for total protein: 6.36 +/- 0.71 gm. per cent. 2. A diet for dogs is described, the feeding of which results in a progressive decline in the concentration of protein in the serum. A composite curve constructed from the findings with 21 animals discloses a rapid initial fall and a slower subsequent decrease in albumin and total protein and an approximately constant level for globulin. The course of the globulin curve was subject to wide variation in separate experiments, both increases and decreases being recorded. 3. With five dogs the nitrogen balance was followed through a total of 42 metabolism periods of approximately 7 days each. The average daily loss of nitrogen was 1.15 gm. Approximate calculations disclose that only 3 or 4 per cent of the nitrogen eliminated is accounted for by the decline in circulating protein, the remainder being represented by loss from the tissues. 4. An episode is described with one dog when, during a period of self-imposed fasting, the serum albumin regenerated to a normal level, apparently at the expense of catabolized tissue protein. 5. The course of serum proteins is described during the recovery which follows interruption of the low protein diet and return to a regime of adequate feeding. 6. A discussion is given of the relationship between tissue proteins and plasma proteins. The data permit one to entertain the hope that a way will be found for stimulating an internal readjustment to provide temporary relief from hypoproteinemia, a way which will depend upon the potential ability of the tissues to provide sufficient protein for the needs of the plasma.

Photochemical Reaction between Hydrogen and Chlorine in the Presence of Oxygen

IT has been generally assumed that the hydrogen chloride produced when a mixture of hydrogen and chlorine is illuminated has no effect on the velocity of reaction. If, however, the magnitudes of the Draper effects are considered for two reaction mixtures which do not differ in hydrogen, chlorine, and oxygen concentrations, but only in the circumstance that one (a) contains no hydrogen chloride, and the other (b) an amount of hydrogen chloride equal, say, to that of the concentration of chlorine, then the magnitude of the Draper effect in (a) can be observed to fall off very rapidly on illumination, while that of (b) shows no such rapid initial fall but is always smaller than the initial value in the case of (a). Indications of a rapid initial fall in reaction velocity in mixtures containing initially no hydrogen chloride can indeed be recognised in the ‘velocity coefficients’ given by several workers; for example, by Bodenstein and Dux.1