of all classes of vertebrate animals, and being absent from the brain, liver, and kidneys of the same animals, it becomes highly probable that it stands in a certain relation to the chemical changes in these organs in which it is found. seems to be a product of the chemical action induced in the muscle by the influence of motion. For in wild and hunted animals, such as foxes and game, the quantity of creatine contained in the muscles is much larger than in domesticated animals. This difference in the amount of creatine produced in the muscular tissue is very strikingly exhibited in the same class of animals.

A fox which had been fed on meat for two hundred days, at the Anatomical Institution in Giessen, did not yield one tenth part of the quantity of creatine which was obtained from an equal weight of the flesh of foxes which were caught by hunting.

The amount of creatine contained in the muscles of an animal stands in a close relation to the quantity of fat deposited in the animal, or to the causes which determine the deposition of fat. From fat meat there are frequently obtained only traces of creatine, and under all circumstances a much smaller quantity than from lean meat with an equal amount of fibrous matter. The above-mentioned fox, which had been fed on meat, yielded above one pound of fat from the peritoneal folds, while in hunted or otherwise chased foxes no fat was perceptible to the eye. The heart of the ox, a never-resting muscle, contains a large amount of creatine, and is therefore frequently used for producing it in quantities.

Creatine is present in the blood, by which it makes its way to the kidneys. It occurs in the urine as a regular ingredient, though present in small quantities only. It is partly transformed into creatinine, most probably somewhere between the muscle and the urinary residue out of which the zinc salt crystallizes. For, in the muscle, creatine has by far the preponderance over creatinine; in the urine, creatinine over creatine. Creatine is, therefore, truly excrementitious: its relation to urca proves this beyond doubt. Its exclusive occurrence

in the muscles shows the seat of its formation; it is, with other matters, a product of the chemical changes in the muscles.

Quantity discharged in twenty-four hours.

This question seems of sufficient importance; but few observations have been made on it. My own experiments, detailed at the end of this chapter, yield 0305 grammes of creatine

discharged in the urine during twenty-four hours, as the average of twenty-six days of two individuals. In disease the quantity of creatine, together with that of creatinine, might serve to indicate the intensity of any spasmodic or convulsive action. The question as to its quantity in tetanic and epileptic disease is one of high interest. Cases of paralysis agitans, in which the spasmodic action ceases with sleep, may perhaps afford good opportunities for demonstrating the influence of rest and motion; though the different nutrition in the muscle may, perhaps, vary the chemical changes in some degree.

These suggestions for future researches must not be mistaken for theories or suppositions.

CREATININE.

The composition of creatinine in 100 parts is as follows:

Creatinine is found in the muscles of the vertebrate animals in small quantities, and in the urine of man in larger quantities than in the muscles. It is the product of the natural or artificial decomposition of creatine, as already described.

Mode of obtaining Creatinine and Creatine from Urine.

The urine is neutralized with some milk of lime, and a solution of chloride of calcium is then added, so long as a precipitate of phosphate of lime is produced. The fluid is then filtered and evaporated until the salts are deposited. The mother-liquor is then separated from the salts (without the use of alcohol), and mixed with one twenty-fourth of its weight of a syrupy solution of neutral chloride of zinc. After the lapse of three or four days, a great part of the chloride of creatinine and zinc, with some creatine, has crystallized in yellow, roundish, warty granules. The deposit is washed with water, then dissolved in boiling water, and to this solu

tion hydrated oxyde of lead is added, until the fluid gives an alkaline reaction to test-paper. The threefold amount of the oxyde of lead used up to this point is now added, and the fluid kept boiling, until it appears to coagulate into a light yellow magma. The decomposition is now completed. Zinc, hydrochloric acid, and lead in the form of the basic oxychloride are thus transformed into an insoluble condition; the substance combined with them before the addition of the lead remains in solution. The latter is now treated with some animal charcoal, which removes a yellow colouring matter and a trace of oxyde of lead, and is then evaporated to dryness. There remains now a white crystalline body—a mixture of two substances, which may easily be separated by alcohol, as the one dissolves easily in boiling alcohol, in which the other is almost insoluble. A portion of the crystalline residue, when heated with eight or ten times its weight of alcohol, either leaves a residue, or dissolves completely; and the solution deposits crystals on cooling: these crystals are identical in their properties with the residue, if any was left. If these crystals are removed from the mother-liquor, and the latter is evaporated, a new crystallization of a different form and different properties is obtained. The body remaining as a residue, or crystallizing first, contains water of crystallization, and is without reaction upon vegetable colours; the other in its watery solution is strongly alkaline, its crystals do not disintegrate by losing water, and the chemical analysis shows that the body which crystallizes first is creatine, and the other creatinine.

Mode of obtaining Creatinine from putrid Urine.

If putrid urine, in which the whole of urea is transformed into carbonate of ammonia, be boiled with milk of lime, until ammonia is not any longer evolved, the fluid then filtered, evaporated to a syrupy consistence, and treated with one twenty-fourth part of its weight of a syrupy solution of neutral chloride of zinc, there will, in the course of a few days, be deposited a considerable quantity of a yellow granular body, which contains chlorine and zinc, and, under the microscope, cannot be distinguished from the zine salt obtained from fresh urine in the manner above described. When dissolved in boiling water, and freed from the chloride of zinc and colouring matter by means of hydrated oxyde of lead and animal charcoal, the organic substance, which was combined with the zinc, appears as pure creatinine without any admixture of creatine.

During putrefaction of the urine, therefore, creatine is decomposed, while creatinine undergoes no change.

Creatine is an accidental and variable admixture of the salt of creatinine with chloride of zinc. A warm-not boilingsolution of creatine is not precipitated by chloride of zinc, and the crystals deposited from it are free from chlorine and zinc, and have the characters of pure creatine.

It is evident that when fresh urine contains creatinine in combination with an acid, and free creatine, the creatinine will be set free by neutralization with an alkali; and if this fluid be now concentrated and evaporated to about one twentieth of its original volume, a combination of creatinine will be precipitated by the addition of chloride of zinc, the crystals of which will, however, be mixed with crystals of creatine, as soon as the latter is present in a larger quantity than the fluid can retain in solution at the ordinary temperature of the air.

Mode of obtaining Creatinine from Creatine.

If creatine be treated with concentrated hydrochloric acid, the solution evaporated, and the dry mass heated in the water-bath until all free hydrochloric acid has been driven out, the residue consists of pure chloride of creatinine. From this salt the creatinine is obtained by boiling its solution in water with hydrated oxyde of lead.

In a similar manner creatinine is obtained from the sulphate, by adding to the boiling watery solution carbonate of baryta, until the fluid shows an alkaline reaction, and no more carbonic acid is evolved. Sulphate of baryta is precipitated, and pure creatinine remains in solution.

Physical properties.

Creatinine, according to Kopp,1 crystallizes in the monoclinometric (clinorhombic) system. The crystals are formed by the prism P, the basic terminal plane OP, and the clinodiagonal terminal plane ∞ P∞. The orthodiagonal is shorter than the clinodiagonal. The angle OP: P∞ (the angle, namely, at which the principal axis is inclined to the clinodiagonal) was found 69° 24. The angle at which the lateral planes P coincide in the orthodiagonal section is = 98° 20' : and accordingly the angle formed by P∞ with ∞ P is = 130° 50'. (vide plate ii, fig. 6.)

=

Liebig, loc. cit. p. 44.

Chemical properties.

Creatinine is much more soluble in cold water than creatine. 1000 parts of water dissolve 87 parts of creatinine, or one part dissolves in 115 parts of water at 60° F. (15° C.) In hot water it is much easier soluble.

The watery solution restores the blue colour to reddened litmus paper. A crystal of creatinine, placed upon a piece of wet turmeric paper, produces a brown stain on the spot where it lies. In concentrated solutions it has a caustic taste, like dilute liquor of ammonia.

Creatinine dissolves in boiling alcohol, and crystallizes from the solution on cooling. 1000 parts of alcohol at 60°F. (15 ̊C.) dissolve 98 parts of creatinine, 102 parts dissolve one part. The chemical character of creatinine is quite that of ammonia.

A moderately concentrated solution of nitrate of silver, to which a solution of creatinine is added, coagulates immediately into a mass of delicate white needles, which are easily soluble in hot water, but crystallize out of it on cooling, without having undergone any change. They consist of a basic combination of creatinine with nitrate of silver.

In a solution of corrosive sublimate, creatinine produces immediately a white curdy precipitate, which, in the course of a few minutes, transforms into a heap of delicate, transparent, colourless needles.

In a watery neutral solution of chloride of zinc, creatinine produces immediately a crystalline precipitate, in the form of roundish, warty granules, which, under the microscope, are seen to consist of delicate needles in zeolithic arrangement. (vide plate iii, fig. 1.)

Creatinine expels ammonia from its salts, and forms blue crystallizable double-salts with the salts of oxyde of copper.

Chloride of platinum produces no precipitate in solutions of chloride of creatinine. If the mixture of the two solutions is, however, evaporated at a gentle heat, dark-yellow, transparent, rather large crystals are formed, which are pretty easily soluble in water, less soluble in alcohol. This salt has a composition similar to the double-salt of chloride of platinum and ammonium.

Combinations.

Chloride of creatinine.-On exposing crystallized creatine