W. F. Von Oettingen

Bronchial Perfusion of Isolated Lung as a Method for Studying Pharmacologic Reactions of Bronchiolar Muscle.

The methods for studying the changes of bronchiolar tone in intact animals are often complicated by changes in the circulation which make their interpretation uncertain. It would therefore be desirable to check them under conditions in which the circulation would be excluded, namely outside of the body. The use of ring preparations of tracheal or bronchial muscle for this purpose has not been altogether satisfactory, partly because these are confined to the trachea and larger bronchi which might react differently from the smaller bronchioles that play the major part in the bronchial reactions; and partly because it is difficult to reproduce the natural conditions of tension. These objections are avoided in the following method, which is based on measuring the rate of flow of a Locke solution through the bronchial tree, allowing the fluid to drain off by filtration. The arrangement is shown diagramatically in Fig. 1. A Mariotte bottle (M) filled with Locke solution is connected with a Woulff bottle (W), also filled with Locke solution, which sits in a bath (B) regulated to keep the temperature of the solution at 39° to 40° C., as indicated by the thermometer (Th). The outflow passes to a tube (T). The upper limb of this is furnished with a short piece of rubber tubing (R) which may be closed by a screwclamp (S). The lower limb is connected with a cannula tied into the short stump of the trachea of the excised lung (L). This should be used either promptly after the death of the animal, or else after lying on ice. In starting the experiment, the T tube is raised so that no fluid flows from the Mariotte bottle; the screwclamp (S) on the upper limb is opened, and the lung is attached to the lower limb. The T is then gradually lowered so that just enough liquid flows into the bronchi to distend the lung approximately to its normal size.

An Entero Depressant Factor in Stools of Monkeys Infected with Experimental Poliomyelitis

Previously, one of the authors (J. A. T.) had demonstrated what was thought to be a toxic factor in the stools of patients ill with poliomyelitis. 1 Was this factor also present in animals experimentally infected with poliomyelitis virus? Stool specimens were first collected from 10 Macacus rhesus monkeys, and the animals were then injected, under complete anesthesia, intracerebrally with potent poliomyelitis virus. Stools were again collected after poliomyelitis had set in. The specimens of feces were dried in vacuo, weighed, ground and enough normal saline solution was added to the powdered feces to make a 10 to 20% suspension. This was then passed through a linen cloth to remove gross particles and debris. Young rabbits weighing 1 to 1 1/2 pounds were etherized, the spinal cord and connections were severed in the region of the tenth thoracic segment, an opening was made, under complete anesthesia, into the peritoneal cavity as described by Sollmann, 2 the intestines were exposed, a cannula connected with a Marriotte bottle attached to the small intestine about 6 inches from the ileocecal valve and the material was introduced into the lumen of the intestine in quantities of 10 cc. This procedure gave a partial spinal animal with nerves and blood vessels intact as far as the piece of gut experimented upon was concerned. The pouch was filled with liquid paraffine at 38°C. The intestinal activity was recorded by a lever connected with the intestinal wall by a silk thread attached to a serrefine. Ten of the 10 stool suspensions obtained before the injection of the poliomyelitis virus acted as irritants and caused an increase in the number and strength of peristaltic waves. One of the injected animals did not contract poliomyelitis.

Destruction of Levo-, Dextro- and Racemic Hyoscine by Egg White and Rabbit's Serum

It was demonstrated 1 that rabbits serum destroys atropine (dl-hyoscyamine) and its isomers, levo- and dextro-hyoscyamine, at different rates and it was suggested that this accounts for quantitative differences of the systemic action of these alkaloids in different species. In the following report levo-, dextro- and racemic hyoscine∗ were studied as to their destruction by egg white and rabbits serum. The determination was performed in the same manner as described in the previous paper. In the first series 20 mg. of the alkaloids were dissolved in 2 cc. of water, mixed with 8 cc. of fresh egg white and incubated for 0, 3, and 6 hours at 38°C, three experiments being done for each compound and each series. At the end of the incubation period the alkaloids were isolated and determined by means of the Vitali reaction. It was found that with all 3 alkaloids without incubation all material added could be recovered within the limit of error which is ±5%; after 3 hours of incubation 21.9% were destroyed and after 6 hours 37.5%, the 3 isomers being destroyed at the same rate. It is interesting that under identical conditions atropine and its isomers were destroyed at thesame ratio, namely ±5%, 21.5%, and 37%, the 3 isomeric forms showing also no differences in regard to their destruction. Similar experiments were performed with rabbits serum in the same proportion and with the precautions discussed in the previous paper. In this series also 3 experiments were made for each alkaloid and each time interval, which all gave identical results. After 6 hours 100% of the levo-, 68.3% of the dextro-, and 81% of the racemate were destroyed, which agrees with the values found in the atropine series, 100% for levo-, 57% for dextro-hyoscyamine and 81% for atropine (dl-hyoscyamine).

Notes on Toxicity and Pharmacology of Indium

Indium was discovered spectroscopically by Reich and Richter in Freiburg zincblende. Although widely distributed in minerals, it usually occurs only in very small quantities, and only recently Westbrook 1 worked out a process to isolate this element in larger quantities from crude zinc liquors which are residues from the manufacturing of sulphuric acid. Indium is a white, lustrous metal, very soft and ductile and slightly heavier than zinc. It melts at 155° and boils at 1450°. It does not tarnish at ordinary temperature, but oxidizes rapidly above the melting point, burning with brilliant violet flame at higher temperature. Chemically it resembles zinc in some respects and aluminum and iron in others. It is trivalent in stable compounds, and its sulphate forms alums with monovalent metal sulphates. Most indium salts are colorless, very soluble in water and hence do not crystallize easily. Alkalies precipitate the white indium hydroxide from the aqueous solutions of the salts, which precipitate may be redissolved by sodium and potassium hydroxide at room temperature, but it is reprecipitated at boiling temperature. Preparation of Indium Solution. The material, for which we are indebted to the Grasselli Chemical Co., was stated to contain 268 gm. of indium chloride per liter. From this a tenth molar solution was prepared, containing 25.1 gm. of indium chloride per liter. This solution was found to have a pH of 1.8, using thymol blue as indicator. Attempts to neutralize this solution by means of alkali were not successful, because near the neutral point the hydroxide was precipitated. The mixture of indium chloride and sodium citrate, using 5 cc. M/10 indium chloride and 10 cc. M/10 sodium citrate can, however, be adjusted by means of alkali to pH 7.2 to 7.4.Indium was discovered spectroscopically by Reich and Richter in Freiburg zincblende. Although widely distributed in minerals, it usually occurs only in very small quantities, and only recently Westbrook1 worked out a process to isolate this element in larger quantities from crude zinc liquors which are residues from the manufacturing of sulphuric acid.Indium is a white, lustrous metal, very soft and ductile and slightly heavier than zinc. It melts at 155° and boils at 1450°. It does not tarnish at ordinary temperature, but oxidizes rapidly above the melting point, burning with brilliant violet flame at higher temperature.Chemically it resembles zinc in some respects and aluminum and iron in others. It is trivalent in stable compounds, and its sulphate forms alums with monovalent metal sulphates. Most indium salts are colorless, very soluble in water and hence do not crystallize easily. Alkalies precipitate the white indium hydroxide from the aqueous solutions of the salts, which precipitate may be redisso...

Bubble Recorder for Mariotte Bottles.

The recording of bubbles passing through a Mariotte bottle by means of a tambour offers considerable technical difficulties, as for instance, in the lung perfusion, described by Sollmann and von Oettingen; 1 nor does the device, worked out by Atzler and Frank 2 give satisfactory records. Very good results have been obtained with the following device which utilizes the oscillation of the fluid in the inlet tube of the Mariotte stopper to close a circuit between 2, pair of wire electrodes adjusted in the lower end of the tube. The electrodes consist of copper wires fused into narrow glass-tubes for insulation, with projecting platinum tips. One wire is adjusted to about one millimeter above the lower rim of the tube, the other wire dips about 0.5 cm. into the fluid. The 2 electrodes are held together by a rubber-ring through which a pin passes, which rests upon the upper rim of the Mariotte tube (Fig. A). By shifting this ring up and down, the electrodes can be adjusted to different levels; they are connected with a current of no volts and with a relay arrangement, the dry cells of which feed a signal magnet, as described by Biskind and Dan. 3 When the fluid within the Mariotte tube rises a little after each bubble, the 2 electrodes are short-circuited, and a signal mark is produced on a moving drum. There is virtually no danger of changing the composition of the saline solution by electrolytic decomposition products, because the contact between saline and electrodes is short, and the quantity of saline coming in contact is very small.