Iodine

IODINE, Iodum (from the Greek ioeides - having a violet color), a solid halogen with the chemical symbol J; atomic weight of iodine 126.932; iodine occupies position 53 in the periodic table of elements, in the 7th row of group VII. It crystallizes in the form of large, shiny, dark gray plates or leaflets of rhombic shape; the odor of I. resembles the characteristic odor of hypochlorous acid; taste is sharp and pungent; sp. gr. 4.93 at t° +4; melts at t° 113.5°, boils at t° 184.35°, and passes into the vapor state at room temperature without melting; vapors are violet in color, from which iodine received its name. The vapors of I. are 8.65 times heavier than air. The molecule of I. contains 2 atoms. When heating the vapors of I. to 1,700°, the molecule of iodine splits into atoms; upon cooling, the atoms combine again into molecules, releasing a large amount of heat: J + J → J₂ + 28,500 small calories. It has been definitely established that the chemical properties of the monoatomic and diatomic forms of I. are different. I. dissolves in water in approximately the ratio 1:6,000; a brownish-yellow liquid is obtained, having bleaching properties. In water containing solutions of hydriodic acid salts, iodine dissolves much more easily, giving with the iodide ion a complex ion J⁺ + J₃⁻; in such cases, aqueous solutions of I. have a dark brown color. Iodine dissolves in 90% alcohol in the ratio 1:10, giving a yellow-brown solution; it easily dissolves in carbon disulfide (with a pink color), in chloroform, coloring the latter pink, and with higher concentrations of I. - violet; soluble in 20 parts of ether, in 200 parts of glycerin. Solutions of I. in alcohol and I. in aqueous solution of potassium iodide are not regarded as simple solutions, but as chemical compounds, unstable in the case of alcohol or reversible (KJ₃ ⇌ KJ + J₂) in the case of KJ. Upon addition of diluted starch paste, the aqueous solution of I. turns blue. Only traces of I. in the liquid being tested are sufficient to obtain a blue coloration with starch paste; therefore, starch paste is a very sensitive reagent for I., and conversely: a weak solution of I. can detect the presence of starch. I. does not form a hydrate with water; its affinity for hydrogen is small: J₂ + H₂ ⇌ 2HJ; this reaction is reversible, and HJ easily dissociates with the release of heat; hydriodic acid HJ, as a little stable compound, decomposes in light at ordinary t° in the presence of oxygen: 4HJ + O₂ = 2H₂O + 2J₂. It combines with many elements: with some metalloids and with most metals. From compounds with hydrogen and metals, it is displaced by chlorine and bromine: 2HJ + Br₂ = 2HBr + J₂. An aqueous solution of I. is an oxidizing agent, converting sulfurous acid into sulfuric acid; a solution of I. in KJ is used in the iodometric determination of oxidizable substances in a given sample. The affinity of I. for oxygen is greater than the affinity for chlorine, but with respect to metals - less. J₂O₃ is the anhydride of iodic acid (HJO₃), existing as a white crystalline powder. I. has the property of forming compounds in the form of salts of periodic acid (HJO₄). The usual method for quantitative determination of I. is the titration of I. with sodium thiosulfate Na₂S₂O₃; the reaction proceeds as follows: J₂ + 2Na₂S₂O₃ = 2NaJ + Na₂S₄O₆; the end of titration is indicated by the indicator reaction of starch coloring. In nature, I. is very widespread, usually occurring in extremely small quantities, mainly in the form of inorganic or organic compounds; however, it can also be found in the free state in the air, which was previously denied on the basis of the work of Gautier. A more modern technique has made it possible to establish that the transformation of I. from combined state to free state occurs in nature, and I. passes into the air, from where it enters the soil, water and plants, where it again passes into the combined state. The cycle of iodine in nature, according to Fellenberg, can be approximately represented as follows: in the most ancient geological epochs, iodine entered into the composition of rocks, which now make up the solid shell of the earth. During the weathering of stone massifs of mountain ranges, the alkali and alkaline earth iodides present in the rocks are constantly washed out. The latter partly remain in place in the soil, are adsorbed by it, forming new compounds with various minerals, and partly are carried away by the waters of local sources, subsequently entering rivers, lakes and finally seas; partly, in addition, due to catalytic processes occurring in the rocks, they decompose, and I. in its pure form is released into the air. The same decomposition of iodides occurs in various water sources up to the vast marine spaces, as a result of which a considerable amount of elementary I. is found in the air in total. Due to atmospheric precipitation, I. from the air returns to the soil and waters, from where it is captured by the most diverse plant and animal organisms, in which free I. again passes into the combined state. During life, animals excrete I. with excreta, and after the death of both animals and plants during their decay, I. partly again passes into the free state or is converted into alkali and alkaline earth iodides, in the form of which it again returns to the earth and water. Thus the cycle of iodine in nature is completed. Some marine plants of the brown algae class (Phaeophyceae), family Fucaceae, Laminariaceae have the property, by accumulating I. in their organisms, to become significantly enriched with it, as a result of which I. is distributed in nature very unevenly. From places and materials with a higher content of I., it is extracted in its pure form. Iodine was first obtained by Courtois in 1811, specifically from marine algae, from the ash of which elementary iodine was isolated. At present, the main source of I. extraction is the Chilean nitrate deposits, from the mother liquors of which, after crystallization of natural saltpeter, pure iodine is isolated. The world market receives annually (1927) approximately 1,100,000 kg of I., of which about 800,000 kg comes from I. from Chile, about 150,000 kg from I. from marine algae, and the remaining 150,000 kg from I. from mineral sources on the island of Java. In our country, the question of I. extraction was raised during the last imperialist war; it began to be extracted from the Black Sea algae - Phyllophora rubra and from the algae of the White Sea, and only an artel of artisans on the island of Zhizhgine, 250 km from Arkhangelsk, managed to establish profitable production, extracting about 400 kg of iodine per year. I. was also extracted from algae on the Far Eastern coast. The drilling waters of oil wells of the Apsheron Peninsula and the drainage production waters, carrying away annually over 450,000 kg of iodine, attract the attention of researchers and workers of the USSR as possible sources of I. extraction; however, their processing is complicated by the low content of iodine, alkalinity and the presence of large amounts of other salts and fatty acids. I. has been found in many regions of the USSR: near Krasnodar, in lakes near Baku, in the waters and muds ejected from the mud volcanoes of the Taman Peninsula, in the muds near Kerch, in the lakes of Siberia, in copper-silver ores of the Far Eastern region and in other areas. In some of the mentioned places, attempts were made to obtain pure I., but due to unprofitability, production was discontinued. I., found in mineral muds (Odessa, Saki and others) and in mineral springs (in the USSR - Borjomi, Zheleznovodsk, Berezovskaya waters), has been used for medicinal purposes. Italian mineral waters (Frescaro, Castrocaro), Romanian (Vulcana, Varfulie and some others), Bavarian Heilbrunn and French Aix-les-Bains are particularly rich in I. in the form of NaJ. I. is found not only in mineral springs, but also in many fresh waters (Neva, Elbe, Seine, Thames and many others). I. is a constant component of the animal and human organism, in some cases found in particularly large quantities (in the sponge Ceratospogonia 8-14% I.). I. is contained in significant amounts in some sponges (spongine, corneine). From corneine of the Gorgonacea group, an iodinated amino acid - iodogorgonic (3,5-diiodotyrosine) C₉H₉O₃NJ₂ - has been isolated. I. in the human organism. In humans, I. is contained in various organs, mainly in the form of organic compounds; the largest amount of it is in the normal thyroid gland - 9.76 mg, less in the liver - 1.21 mg, in the kidneys - 1.05 mg, in the skin and hair - 0.88 mg, in the nails - 0.8 mg; even less in the mammary glands - 0.65 mg, in the adrenal glands - 0.63 mg, in the ovaries - 0.61 mg, in the spleen - 0.56 mg, in the testes - 0.5 mg, in the pancreas - 0.43 mg, in the lungs - 0.32 mg, in the brain - 0.2 mg and in the blood (per 1 liter) - 0.021 mg.

I. enters the human organism in very minute quantities with the air, with drinking water, and salt, and in significantly larger amounts with plant and animal food, with green vegetables, eggs, milk, river and sea fish being relatively rich in I. For the first time in 1895, Baumann (E. Baumann) proved the presence of I. in the thyroid gland of humans (healthy and suffering from goiter), as well as in animals—sheep, cows, horses, pigs, rabbits, and dogs. The cited author isolated from the thyroid glands a special iodine-containing body, which he named thyrojodin, or iodothyrein; it is not an individual substance; its iodine content varies greatly. Oswald (A. Oswald) showed that the genuine iodine-containing body of the thyroid gland is the globulin found in the colloid of its follicles—iodothyroglobulin. In 1919, Kendall crystallized thyroxin from the thyroid glands. Thyroxin (according to Harington) has the formula C₁₅H₁₁O₄I, contains 65.4% iodine; it has an effect on the organism characteristic of the thyroid gland and is considered its hormone. In healthy inhabitants of those areas where goiter rarely develops, the amount of iodine in the thyroid glands is usually higher than in inhabitants from areas not «73 favorable regarding goiter. In patients with goiter, the percentage content of I. in the gland is significantly less, while the absolute amount is close to normal figures. However, in individual cases, the complete absence of I. in the thyroid gland has been unequivocally proven; on the other hand, conversely, Baumann sometimes found much iodine in colloidal goiters. This same researcher noted that in healthy inhabitants of the city of Freiburg (Baden), where goiter exists endemically, the total weight of the thyroid gland is very high, but the percentage content of I. in it is insignificant. Normally in childhood and youth, I. in the gland is less than in adults, and in the elderly—very little. In women with maturity, the amount of I. in the gland increases, while during pregnancy it decreases. In newborns, I. in the thyroid gland is very little, so many authors did not find it at all, nor did they discover it in the thyroid glands of embryos. When entering the organism from the external environment, I. is predominantly deposited in the thyroid gland, where it is converted into a special organic compound, which is the hormone of the gland. Iodine in the gland is also present in the form of salts of alkali metals. According to Blum and Griitzner (Blum, Griitzner), in the organism of healthy individuals, iodoprotein compounds do not exist in any organs except the thyroid gland, and only a small amount of organically bound I. has been found in the blood of patients with eclampsia; it is believed that in these cases I. is of thyrogenic origin. The aforementioned authors did not discover that in other diseases, the breakdown of iodine-containing substance occurs in the thyroid gland with the release of organically bound I. into the blood. However, Blum's conclusions are not fully confirmed. Some authors (Veie, Sturm), using Fellenberg's method for determining iodine, established that on average 65% of the circulating organic I. in the blood accounts for organic I., and 35% for inorganic I.; Fellenberg, however, indicates an even smaller percentage for the latter—18%, noting that in various organs of the body I. is present not only in the form of inorganic salts but also in the form of specific organic compounds. In diseases of the organism, accompanied by functional disorders of the thyroid gland in the direction of its hyperfunction or hypofunction, sharp fluctuations in the content and distribution of I. in the organism are observed, associated with the changing properties of the diseased thyroid gland to either absorb I. and accumulate it or to give it up extraordinarily quickly; thus, in hyperthyreosis, the iodine-containing hormone formed in the gland is released by the gland into the blood very quickly; in cretins, the amount of I. in the blood is significantly lower than normal, while the accumulating capacity of the thyroid gland is also reduced. The main pathway for the excretion of I. from the organism is the kidneys, as well as the salivary, sweat, and lacrimal glands, bile, milk (in the form of iodinated fats), and the gastric mucosa. Through the kidneys, the excretion of I. begins very soon (3-18 minutes), but depending on the amount of I. introduced, it continues from 11-25 hours to 8-20 days. The addition of mucous substances to iodine preparations delays the beginning of excretion, probably due to slowed absorption. Saltpeter and table salt increase the excretion of I., while sodium bicarbonate does not affect the speed of excretion. Research has shown that the amount of I. excreted by the kidneys is always less than the amount introduced, even if huge doses are introduced into the organism. 30% or in the best case 14-15% of the total amount of introduced I. is missing. A relatively significant amount of I. is excreted in saliva, and depending on the absorption rate of the preparation, I. quickly appears in the saliva. The presence of I. is found in milk when it is introduced into the organism. Stumpf (Max Stumpf) found that in a woman who received 5.0 g KI, 0.109 g I. was excreted with the milk. Only traces of I. are found in the feces. The above data refer to cases of introduction of inorganic I. preparations, which are easily absorbed from mucous membranes and very well with subcutaneous injections. Absorption of I. has also been detected through the skin when using potassium iodide in ointments. Of organic compounds of I., absorption and excretion occur as it is cleaved off, consequently when it passes into an inorganic compound of I., but in this case the amount of I. excreted in the urine is relatively less than the amount of I. in the urine when taking KI, and excretion occurs much more slowly and usually more evenly than when giving KI. However, in the feces after taking organic iodine preparations, I. can be easily found in much larger quantities than after inorganic compounds. This can be explained by the fact that some organic compounds of I. are either slowly or not at all broken down by either gastric juice or pancreatic juice, so one part of the taken preparation, not being absorbed, passes through the intestine unchanged. The other—larger—part of this undigested substance in the gastrointestinal tract, after being absorbed, undergoes slow breakdown in various tissues, and thus the transition of I. into the urine is relatively delayed. What has just been said generally applies not only to preparations from the series of iodinated fats, fatty acids or their esters, but also to iodoprotein preparations, whose fate in the organism has been studied insufficiently. The effect of I. on the organism. The local effect of I. is easiest to trace using a concentrated solution of iodine-T-ra Jodi (Tinctura Jodi)—for action on living tissues. When rubbing tincture of iodine on human skin, it is colored a saturated reddish-brown color, quickly turning yellowish due to the volatilization of I. from the skin surface. At the site of rubbing, a feeling of heat and burning appears, the skin reddens, and due to the direct action of I. on the sensitive nerve apparatus of the skin, a loss of sensitivity occurs to some degree. After repeated rubbings, the upper layers of the epidermis die and peel off. With particularly intense application of the tincture on the skin, blisters with serous, and later even with purulent, contents form. The vessels appear dilated, and the walls become swollen, edematous, and become easily permeable to wandering cells. White blood cells not only enter the skin tissue itself but also penetrate the subcutaneous tissue and further into deeper-lying parts—into the intermuscular tissue and into the periosteum of nearby bones. After several days, a regressive metamorphosis occurs, leukocytes and tissues undergo fatty degeneration, dissolve, and are removed (Binz). In this way, pathological products located in the area of action of iodine tincture can easily be removed by resorption. The irritating effect of I. is willingly used in the treatment of prolonged inflammatory processes, such as: tumors of lymph glands, inflammations of lymph pathways, inflammations of the periosteum, synovia and tendon sheaths, serous skin effusions, etc.—An even stronger effect of I. is exerted when its solution is introduced into serous cavities (e.g., in hydrocele) or into the cavity of a cyst. Severe irritation develops, inflammatory phenomena with abundant exudation of fibrinous exudate occur, and finally, the cavities close due to the so-called adhesive inflammation.—Since I. quickly enters into compounds, in such cases it changes the composition and properties of the bodies entering into reaction with it, the destructive effect of I. on microorganisms is great, and it is a very energetic antiseptic agent. Rubbing the skin, mucous membrane, and small wounds with a solution of I. is widely used in surgical practice for the local sterilization of tissues. The energetic effect of I. on cellular protoplasm in general is the basis for the use of iodine as a locally irritating (up to cauterizing) agent.

The local application of I. is usually accompanied by the entry of I. into the blood, i.e., absorption, since the ability of pure I. to be absorbed is extremely great; I. is especially easily absorbed through mucous membranes and wound surfaces. In the question of absorption, attention is drawn to the circumstance that when I. is introduced internally, it is very little absorbed by the healthy mucous membrane of the stomach (Metzger, Mering, Boas). In the body, after absorption, I. is distributed very unevenly to different organs; however, this depends, like absorption, on the choice of preparation. When using KJ, iodine enters most of all into the thyroid gland and the skin, less into the blood, lungs, and stomach, even less into the lymph glands, the right lobe of the liver, salivary glands, and kidneys; in the remaining parts of the body - muscles, testicles, left lobe of the liver, small and large intestines - I. is deposited very little, just as in the brain; in the spinal cord, bones, and fatty tissue, I. is not found at all (O. Loeb). In the brain, I. is deposited in the form of an organic compound, which is very unstable. It is very important not only from a theoretical point of view but also in a therapeutic regard that I. accumulates especially abundantly in tissues affected by syphilis; according to Loeb, in gummatous neoplasms, I. is 6.2 times greater than in the blood; in this case, I. is mostly in the form of a compound with proteins. The property of pathologically formed tissues to enrich themselves with I. at the expense of administered iodine preparations is noted not only in syphilitic neoplasms but also in cancerous tumors and tissues affected by tbc. The influence of the accumulated preparation in such cases becomes understandable from the concept of the general effect of iodine compounds. When iodides circulate in the body, e.g., KJ or NaJ, then due to the vital activity of cell protoplasm in the presence of active O₂ and CO₂, free I. is split off. This fact was first established by Bincz in relation to KJ: on KJ, the living protoplasm of the plant Lactuca sativa, acidified with CO₂, acted in a decomposing manner, with free iodine being released. The reaction proceeds according to the following formula: KJ+H₂O+CO₂=KHCO₃+HJ; 2HJ+O=H₂O+J₂, i.e., CO₂ first decomposes KJ in such a way that potassium bicarbonate and hydroiodic acid are obtained, and the latter is immediately decomposed by oxygen, since the chemical affinity of hydrogen for oxygen is significantly stronger than for I. Only in the presence of living protoplasm is it possible to isolate free I., because living protoplasm has the property of easily activating the oxygen of the air necessary for the final phase of the process of I. release. The experiment does not succeed with dead protoplasm. The splitting of iodides with the release of free I. also occurs in the presence of nitrous acid or its salts; therefore, an acidified solution of KJ is decomposed by the addition of human saliva, which always contains nitrous acid salts in its composition. Thus, it can be stated that in the human and animal organism there undoubtedly exist suitable conditions for the decomposition of iodine salts with the release of free I. - the living protoplasm of cells that converts atmospheric oxygen into an active form, a sufficient amount of carbon dioxide, the presence of nitrous acid salts. Bincz writes that "in view of the fact that certain kinds of tissue swellings are cured by the internal use of KJ, it is very natural to assume that the release of I., observed in the action of CO₂ and protoplasm, constantly occurs in these tumors as long as KJ circulates in the blood, and that as a result the pathologically multiplying cells gradually perish." The split-off iodine, due to its properties, easily enters into new compounds, is not deposited in tissues, but again combines in them with proteins, alkalis, lipoids, and under certain conditions is again split off. Due to such easy transformability of iodine compounds with constant release of I., their action in the body can be represented with great probability as the action of pure I., which has the property of causing phenomena of irritation of varying intensity at the place of its location in tissues, and thus to produce local inflammatory phenomena or an exacerbation of such, if they already existed. The mentioned phenomena, already mentioned in the exposition of the local action of I., in many cases end with phenomena of regressive metamorphosis and resorption of pathological formations and products as less stable in comparison with normal ones. The authors note that in syphilitic processes there may also be a specific action of iodine on the pale spirochete as an antiseptic substance. Bincz's theory of the action of iodine compounds by the splitting off of iodine met with objections, but they were unconvincing, as they were refuted on the basis of experimental data. Burgi (E. Burgi) therefore comes to the following conclusion, confirming the opinion of the splitting of various sub-compounds with the release of free I.: "Iodine salts, after being absorbed, first circulate in the blood as such; then most of them dissociate, and then part of I. forms organic compounds, while part is adsorbed; in the tissues, I. is found in the form of organic and inorganic compounds; part of I., under suitable conditions, is also in a free state; in the urine, I. mostly passes in the form of iodine salts, a little in the form of iodates, and partly in an adsorbed state with organic substances." If iodine is introduced in organic compounds, then part of the iodine passes into a free state already in the gastrointestinal tract; the absorption and excretion of organic I. preparations occurs in general more slowly than iodine salts; especially slow - iodine-lipoid compounds. In the feces and urine, I. is mostly in a bound state; in the blood - partly in the form of organic compounds, partly in the form of soluble ether compounds; in the organs, mostly iodine-organic compounds are deposited, and only a little free iodine is found. Iodine-lipoid preparations belong to neurotropic and lipotropic compounds; other iodine preparations either do not show such properties at all or manifest them to a very small degree. When using various preparations, free I. is retained in the greatest quantity in the thyroid gland. With subcutaneous administration of large doses of I. solution, the mucous membrane of the stomach becomes hyperemic, cloudy swelling appears in its epithelial cells, the intestines are also hyperemic, but to a lesser degree; in the liver, fatty degeneration occurs, in the kidneys - inflammatory phenomena, hematuria, hemoglobinuria; in the urine - cylinders, protein, renal epithelium; the excretion of urine first increases, then sharply decreases; the case ends with uremia. Blood pressure remains unchanged if the amount of I. in the blood does not exceed 0.7%; the pulse remains normal; at 1% iodine in the blood, blood pressure is lowered, the work of the heart weakens, and finally, if there is no less than 1.67% I. in the blood, the heart stops. The arrest of an isolated frog's heart occurs in the presence of I. 1:10,000 in Ringer's solution, but with a weaker concentration of I. (1:30,000) the heart contractions become more frequent, irregular, and the work of the heart decreases. Large doses of I. cause depression of the nervous system and often collapse. When inhaling iodine vapors in humans, headache, lethargy, depressed state, drowsiness, fainting, and depression were noted, which indicated the action of I. on the central nervous system. As a halogen, I. should possess narcotic properties, which in general is confirmed by observations on humans and animals; but it is very difficult to trace all phases of narcosis in animals in the experiment, since the locally irritating action of I. on the respiratory tract quickly disrupts the function of the respiratory apparatus, damaging it; the mucous membranes of the pharynx, larynx, and bronchi become hyperemic, edematous, the lung tissue also edematizes, especially in the lower lobes; the exudative process also involves the pleura; the animal begins to suffocate. The experiment of narcosis with I. vapors can be carried out more calmly only on a frog. When moderate doses of pure iodine are introduced into the body, an increase in the strength of heart contractions, dilation of blood vessels, and a decrease in blood viscosity were noted. However, many authors dispute the influence of iodine on blood vessels and blood viscosity. It is also difficult to establish how pure I. acts on metabolism, and in this case the conclusions of researchers are very contradictory. Some authors assert that metabolism remains unchanged with iodine; others observed increased excretion of nitrogen, increased excretion of urea, total nitrogen, phosphorus, and chlorine. The solution of the question is very difficult due to the participation of the thyroid gland in metabolism (see). The influence of I. is also manifested in the increase of oxidative and catalytic processes in the body. Kepin showed that I. increases the autolytic ability of the liver. Nikulin determined that the protease of blood serum increases under the influence of iodine; the amount of lipase increases even more; autolytic processes intensify in the liver, lungs, uterus, ovaries, testicles, and pancreas.

Iodide salts, as well as organic iodine preparations, when introduced into the organism, in their action on it belong to indifferent compounds not possessing any characteristic action. But as soon as the cleavage of the introduced iodide compound begins, the released iodine exerts its inherent action. For this reason, one usually speaks not of the action of this or that iodine-containing preparation, but generally of the action of I., or, more precisely, of the action of the I. molecule. NaJ, introduced intravenously into a dog in a very large dose (0.8 per 1 kg), after only 8-10 hours causes in it lassitude, weakness, shortness of breath, pulmonary edema, exudative pleurisy, and edema of the lower lobes of the lung; the animal dies 12-40 hours after the injection from paralysis of respiration. A dose of about 0.81 per 1 kg of body weight is considered lethal for a rabbit. With such an amount, disturbances of the nervous system are observed in the rabbit-the rabbit lies on its side, moves with difficulty, the hind limbs are paralyzed, reflexes are heightened, slight touch causes convulsions that sometimes occur spontaneously; the pulse is slowed, respiration is difficult, shortness of breath appears; appetite disappears, diuresis is increased, there are diarrhea; body weight falls. The animal dies from paralysis of respiration. The main changes found on autopsy are in the region of the lungs and liver. The liver is fatty degenerated, necrosis of cells is found in places; the lungs are greatly hyperemic, edematous, especially in dogs; in these same animals, a large amount of exudate is usually found in the pleural cavity, which greatly hinders respiration during life. In the exudative fluid, much KJ and NaJ are found. In the kidneys-there are signs of nephritis, not sharply expressed. The human organism is quite sensitive to iodide salts, but cases of extraordinary endurance to these preparations are also encountered. Bintz knew a patient suffering from psoriasis; she took 1,920 grams of potassium iodide over 102 days; some patients reached doses of 50.0 per day. In cases of idiosyncrasy to iodine and its preparations, which are so common, as well as during prolonged treatment with medium doses of iodide salts, the following signs of acute poisoning by I. (iodism) are observed. Inflammatory phenomena of the mucous membranes-nose, larynx, pharynx, frontal sinuses, maxillary cavities, eyelids; severe rhinitis, severe pain in the region of the frontal sinuses, middle ear, often unbearable headaches, edema of the eyelids, swelling in the region of the larynx, severe bronchitis, sometimes acute edema of the vocal cords; in tuberculosis of the lungs, hemoptysis may begin; salivation, swelling of the tonsils and parotid glands; exacerbation of urethritis; the stomach usually does not suffer, but appetite may disappear; there is also vomiting; sometimes irritation and pain in the intestine are observed. There are indications of atrophy of the mammary and seminal glands with long-term use of iodide salts. In iodism, skin rashes are common and very characteristic, sometimes arising acutely in the form of petechiae, more often acne, less often-in the form of edemas, phlegmons, eruptions of the pemphigus type, etc., sometimes having a chronic course in the form of so-called iododerma, and it is not difficult to prove the presence of I. in the pustular rash. Patients suffering from iodism often complain of insomnia, pains, especially agonizing in the region of the trigeminal nerve, palpitations, increased excitability, and sometimes of emaciation. It has been noted that the phenomena of iodism arise particularly quickly with the introduction of ammonium iodide, which Bintz connects with the extraordinary ease of decomposition of this compound compared to KJ or NaJ. Ammonium iodide already spreads and decomposes on air into ammonia and free iodine: NH₄J=NH₃ + HJ; 2HJ + 0 = H₂O+J₂. The phenomena of iodism easily pass after the cessation of iodide preparations. To prevent acute poisoning during treatment with iodine, it is recommended to start treatment with relatively small doses, gradually increasing them if there are no symptoms of iodism; after taking the medicine, it must be washed down with 1/2-1 glass of milk or alkaline drinks. With repeated courses of treatment in patients, a habit to iodide preparations develops, and then patients tolerate I. more easily. Almost all the phenomena observed in the body in iodism can be easily explained if one adheres to Bintz's theory of the action of iodide preparations. Thanks to the same theory, it is not difficult to understand the reason for idiosyncrasy to iodide preparations, one only needs to imagine that the formation of hydroiodic acid from salts and its further decomposition with the release of free I. occurs in a particular subject to a greater extent depending on especially favorably developed conditions in the body; such conditions are the increased oxidative capacity of the protoplasm of cells, the presence of CO₂ and a significant amount of nitrate salts. In studying the effect of iodide salts on metabolism, no consistent results have been reached, and therefore in this question it is expedient, following Bintz's theory, to consider the phenomena of iodine cachexia and various changes in the excretion of urea, nitrogen, phosphorus, chlorine, changes in body temperature, etc., not as a result of a special specific action of iodide salts, but as a consequence of those changes and disorders that occur in the body with prolonged use of iodine preparations. The effect of iodide salts on blood vessels, on the activity of the heart, on the viscosity of blood does not appear constant, and the favorable therapeutic effect of iodides in arteriosclerosis and some other diseases often also depends on secondary phenomena that occur in connection with the release of I. Among modern clinicians in this respect, the theory of irritative action is most consistently and vividly carried out by Bier (A. Bier), who recommended the use of small doses of I. in inflammatory processes, proceeding from the position that the diseased organism and especially the diseased focus are extremely irritated and for therapeutic effect small doses of iodine are useful, not large ones. At the same time, however, Bier goes to extremes, attributing to iodine a "specific" action in the sense of homeopaths when they speak of the so-called "organ-specific remedies". - Iodide salts promote the absorption and excretion of other substances from the body, for example mercury and lead, and the amount of lead excreted increases as the total dose of KJ increases, and the time for the excretion of lead decreases. Eisner, noting the special merit of the chemist Melsens, who in 1843 first recommended the use of KJ in chronic lead poisoning, experimentally clarifies the mechanism of such action: from KJ and lead a soluble molecularly-dispersed compound with increased dialysis ability is formed, while the adsorptive properties of lead are reduced. These conditions promote the excretion of lead from the body through the kidneys. The effect of KJ on the excretion of mercury consists in the fact that KJ promotes greater solubility of mercury albuminates and prevents the deposition of mercury in the liver. Iodide salts begin to be excreted from the body very quickly, so that in the first 2-12 hours, depending on the size of the dose, half or somewhat more of the introduced iodides is excreted; the first traces of I. can be found in the urine after the introduction of iodides per os after 9-18 minutes; excretion ends with a single dose after 23-18 hours, and the rate of excretion depends on many conditions. First of all, the kidneys must be healthy; with diseased kidneys, excretion of iodine is difficult, and symptoms of iodism can easily arise. Furthermore, with large doses, as well as with repeated doses, iodine is excreted for much longer and can still be found in the urine on the 10-11th day after the last administration; with muscular work, the rate of excretion increases, and I. appears in the urine on the 10-11th minute instead of the 17-18th-at rest; at night, excretion of I. slows down, in the morning and after lunch it accelerates; in febrile patients it slows down; in struma, large fluctuations in the rate of excretion of I. are observed; iodides taken on an empty stomach appear in the saliva after 5-11 minutes, and those taken after food-after 20-37 minutes. What has been said about the rate of excretion of KJ generally also applies to other iodine compounds-sodium, ammonium, calcium, and iron. The places of excretion of iodide compounds are the same paths as were indicated above in relation to pure I. In the excretion of potassium iodide in urine, I. is found mostly in inorganic compounds-iodides, and partly (about 10%) in organic compounds; with very large doses of iodine preparations, I. may appear in urine in the form of sodium iodate-Na JO₃. From what has been said about the excretion of iodides, it is obvious that iodide compounds introduced in solutions per os are absorbed very easily; they are also easily absorbed if applied to the mucous membranes of the eyelids, introduced into the vagina, or in the form of spray get into the lungs. However, data on the absorption of iodides by intact skin are contradictory. Javein, having studied the question of the absorption of KJ by intact human skin from aqueous solutions-baths, came to a negative conclusion; in recent times, however, there are still defenders of the view on the absorption of iodides by intact skin.

If one takes into account that not only in clinical observations but also in experimental studies it is very difficult to guarantee the complete integrity of the skin when rubbing in ointments or when applying compresses, it becomes understandable that through unnoticed skin injuries iodides penetrated inward, and as a result the authors could have obtained false positive data. When administered per os, iodized fats, fatty acids and their esters are generally absorbed with some delay; however, the excretion of the I. contained in them is very prolonged, and accordingly the I. compared to iodides remains in the body for a very long time. For example, after the administration of iodipin, I. was still found in the urine on the 11th day; iodival and iodglydin are absorbed as quickly as KJ, but are excreted much more slowly and evenly. There are also other differences between iodolipids and iodides: after the administration of lipids, a significant amount of I. is often found in the feces; after lipiodin, there is much I. in the milk. Some lipids are not broken down in the stomach at all, or only slightly in the intestines, and yet after their administration per os, iod appears in the saliva very soon (sajodin). The excretion of I. from the body when taking lipids can be accelerated by subsequent administrations of KJ or by consuming food rich in fats. Once in the body, iodized fats initially circulate in it as indifferent substances; subsequently, under appropriately favorable conditions, I. is cleaved from them, which determines the main therapeutic value of iodolipid preparations. Another group of organic iodine compounds, iodoproteins, occupy an intermediate position in terms of absorption rate between iodides and iodolipids, being closer to the former. However, the excretion of iod taken in proteins occurs more slowly and begins and ends significantly later than with iodides. The amount of iod that passes from administered iodoproteins into the urine with organic substances is much higher than with iodides and lipoids. The essence of the action of iodoproteins and iodolipids again comes down to the irritant effect of the cleaving I. molecule or to the action of the thyroid gland in connection with its ability to enrich itself with I. The peculiarities of the action of some iodoprotein preparations, such as the selective action on the heart in a study by Nikolaev of a preparation made in 1903 by the firm Böhringer (Boehringer und Söhne, Mannheim), suggest as if the action of the preparation is due to a special iod-containing molecule; but in this respect one can only make assumptions until the exact composition and properties of these bodies are known. Therapeutic value of iodine. The therapeutic value of iodine, as well as its preparations, is determined by its local irritant, cauterizing, antiseptic action, its property to promote resorption, reduce sensitivity, and facilitate the elimination of heavy metals from the body; therefore, I. and its preparations are used in many diseases; externally - for small injuries, for exudative pleurisy, for chronic effusions in joints, neuralgias, tumors of lymph glands, syphilitic gummata, eczema, psoriasis, lupus, etc.; for inflammatory processes on the mucous membranes of the nose, mouth, pharynx, larynx, eyelids, vagina, uterus, in the treatment of ulcers and wound surfaces, for disinfection of the skin during operations, etc.; for washing pathological cavities and cysts with the aim of causing the walls to adhere, e.g., in hydrocele, liver echinococcus, fistulous tracts, ovarian cysts; for intrauterine smearing in abortions, etc.; internally: for syphilis, arteriosclerosis, angina pectoris, goiter, scrofula, lesions of bones, joints and glands, for asthma, for resorption of various kinds of chronic infiltrates and exudates, for gout, chronic rheumatism, for poisoning with heavy metals (Pb, Hg) for their more rapid elimination from the body. For diagnostic purposes - to determine the absorptive capacity of the gastric mucosa. After Baumann's discovery, when a regularity began to emerge between the iodine content in the thyroid gland and its functional activity, goiter began to be associated with a deficiency of iodine in the body, and therefore it was proposed to give iodine in small doses for preventive purposes to all people living in areas where goiter occurs as a pandemic disease. This idea of preventing goiter with extraordinary energy was taken up by factories producing iodide preparations, and through the press widely spread this idea among the masses, propagating the idea under the banner of necessary measures in the interests of public hygiene. The press, without considering that food, water and air almost always contain enough iodine, without taking into account that even small amounts of iodine with its constant administration can cause symptoms of iodism and Basedow's disease, without regard to the individual condition of individual citizens, urgently recommended the mandatory addition of iodide preparations to food. On the basis of such propaganda and on the basis of the empirical use of small doses of iodine, begun in the 1860s in France, the opinion was strengthened that the addition of small doses of sodium iodide (0.005 NaJ per 1 kg NaCl) to table salt used for food serves as a preventive measure that prevents goiter diseases. With small doses, Neisser successfully treated patients with Basedow's disease occurring with symptoms of dysthyreosis; but in pure forms of hyperthyroidism, the same microdoses caused an exacerbation of all symptoms. Therefore, those researchers are right who assert that with regard to the action of small doses of iodine, the information is far from complete, especially if one takes into account the peculiar action of thyroid gland preparations and the very active thyroxine. Therefore, the question of the preventive use of iodine should still be considered open. The question of the action of small doses of iodine on the vessels has been raised in recent times (1928) by Guggenheimer and Fischer in connection with the successful use by the authors of an aqueous solution of potassium iodide and bromide, 0.2 each in 200.0, by the teaspoonful three times a day in mild degrees of nonsyphilitic cerebral sclerosis, when functional angiospastic phenomena prevail in the clinical picture of the disease. By experiments on animals, the named authors convinced themselves that when sodium iodide is diluted within the limits of 1:100,000 and up to 1:5 million, the coronary arteries dilate and the stronger the smaller the dose of I. administered. However, the mechanism of action of I. has not been clarified by the authors. Small doses of iodine, taken in pure form (Tinctura Jodi and Solutio Lugoli) or in the form of iodides, are often used to treat already developed arteriosclerosis or to prevent its development. According to Romberg and other authors, the benefit from iodides in these cases is due to a decrease in blood viscosity and consequently a significant improvement in blood circulation due to a reduction in the friction of blood against the vessel walls and at the same time a lowering of blood pressure, which is usually elevated in arteriosclerosis. Koranyi proves the value of iodine preparations as a preventive measure against sclerosis. However, subsequent studies have not confirmed the facts just cited. Blood viscosity after iodine does not always decrease, and in some cases even increases. The method of determining blood viscosity itself is not yet sufficiently developed and can lead to incorrect conclusions. Clinicians have different opinions on the preventive effect of iodine on arteriosclerosis, and the mechanism of action of iodine in such cases remains unexplained: they stop at the assumption that iodides, being easily absorbed in tissues and excreted from them, change and accelerate the diffusion processes in cells, thereby facilitating metabolism and resorption in diseased tissues. The use of preparations obtained from the thyroid gland, as well as the action of the gland itself, are considered separately (see Thyroid gland), as is iodoform (see) and mineral waters containing iodine (see Mineral springs). From iodine, some dyes are made - erythrosine, cyanine, pink bengal. Iodine is widely used in chemical work as a reagent for qualitative and quantitative determinations; some of iodine preparations also serve as reagents. Iodine preparations. Inorganic preparations. Iodine tincture, Tinctura Jodi, Solutio Jodi spirituosa (Ph VII) - a solution of 1 part of sublimed I. in 9 parts of 95% ethyl alcohol; the tincture in thin layers is transparent, of a dark, reddish-brown color, with an iodine odor, volatilizes at ordinary temperature; specific gravity 0.880-0.883. Used externally, as indicated above, for smearing the skin and mucous membranes, often mixed with glycerin 1:2 and 1:3, for washing cavities; internally 1-4 drops, preferably in a KJ solution, or in syrup or tragacanth mucilage. The single highest dose is 0.2. A solution of iodine in oxygenated vaseline (2-4.0 in 30.0 vaseline) is called iodvasogen (Jodvasogen); used externally and internally (10-12 drops) instead of iodine tincture. Instead of iodine tincture, Lugol's solution is often used, Solutio Jodi Lugoli, prepared according to the German and American pharmacopoeias from 10 parts of pure I., 20 parts of KJ and 170 parts of distilled water.

The action of Lugol's solution is more moderate than that of tincture of iodine.-Iodide of ammonium, Ammonium jodatum, NH₄J, a white or slightly yellowish crystalline powder, browning on exposure to air and light; easily soluble in water, less so in alcohol; easily altered on storage. In pharmacological and therapeutic respects it possesses great activity, but easily causes side effects (iodism). Internally 0.1-0.6 in solution, to which simple syrup or ammonia-anise drops are added with the aim of weakening decomposition; externally in the form of ointment-1.0 in 25.0 of fat (olive oil).-Iodide of potassium, Kalium jodatum (Ph. VII), KJ, colorless cubic crystals, slightly moist only with considerable air humidity, saline-bitter taste; dissolve in 0.75 parts water, in 12 parts alcohol; solutions of neutral reaction. With internal administration of large doses of KJ, weakening of the heart's muscular activity is noted, which is connected with the action of the salt's cation. Internally: in aqueous solution 0.5-1.0-3.0 per dose, up to 5.0-10.0-20.0 per day, preferably without any admixture, sometimes in pills, rarely in powders and cakes; for parenchymatous injections-2% solution 2-5-10 cc^g. Recently KJ, as well as sodium iodide, in the treatment of syphilis has been used intravenously (in 10% solution 10.0-20.0 pro dosi with two-, three-day intervals). Externally: in ointments with lanolin or vaseline 1:10 (in ointments with animal fats it quickly decomposes, releasing free iodine,-browning; addition of a small amount of sodium thiosulfate removes the browning). According to Ph. VII the official ointment with potassium iodide-Unguentum Kalii jodati (214 parts of purified lard, 100 parts of anhydrous lanolin, 1 part of sodium hyposulfite, 40 parts of potassium iodide and 45 parts of water); to this ointment pure iodine is sometimes added; then sodium hyposulfite need not be taken. For gargles KJ 1-3.0 in 100.0; for inhalations 0.5-0.25 in 500.0 water; for eye drops 0.3-1% solution; instead of internal administration KJ is used in the form of enemas and suppositories.-Iodide of sodium, Natrium jodatum, NaJ (Ph. VII), colorless, transparent cubic crystals or white crystalline powder of saline taste, moist on air; dissolves in 0.6 parts water and in 3 parts alcohol; solutions of neutral reaction. In diseases of the heart it is used in therapy preferably before KJ, also in cases of intravenous administration, for which purpose a 1% solution is used. To prevent iodism phenomena, as with KJ, bromides are simultaneously given to the patient; when used internally-the same doses and forms as for KJ.-Iodate of sodium, Natrium jodicum, NaJ0₃, a white crystalline powder, dissolves in 20 parts water, is excreted in the urine in the form of iodide, but if large doses are used, sodium iodate also passes into the urine; decomposing, it acts by iodine and the separating oxygen in statu nascendi strongly antiseptically; it is used instead of iodoform in the treatment of wounds in the form of a powder, usually 1 part with 9 parts of boric acid, in ulcus molle and syphilitic ulcers, for insufflations in catarrhs of the nose and larynx, in otitis, etc. Internally in bronchial asthma, in diseases of the heart and blood vessels, in neuralgias and peripheral nerve paralyses 0.3-0.5 in pills two to three times a day. It irritates the stomach and intestines.-Pregl's iodine solution, Jodsolutio Pregl (Jodlosung nach Pregl), is prepared by a method kept secret by the inventor and is said to consist of 0.035-0.04 free iodine and sodium iodide, iodate, and hypoiodite. It is used in septic processes for injections into the abdominal cavity, for washing the bladder, in the treatment of wounds. Organic preparations of I. Alival, Alival, iododihydroxypropane CH₂J.CHOH.CH_aOH, contains 63% I.; colorless, silky crystals; very soluble in water and alcohol; used in lues, arteriosclerosis, goiter, etc.; internally in tablets of 0.3 three to six times a day; under the skin 1.0 in solution (sold in ampoules); rectally in suppositories of 1.0.-Jodalbacid, Jodalbacid, s. Jodalbumin, a yellowish powder representing a compound of sodium with iodinated protein; it swells in water, dissolves when heated with a large amount of water, contains about 9% I.; internally-instead of iodides, since, being difficult to decompose, it does not cause iodism; doses 0.5 - 2.0 several times a day.-Jodalbin, Jodalbin, an iodoprotein compound with 21.5% iodine, a powder soluble only in alkaline liquids; used instead of KJ to avoid iodism phenomena; for the same purpose other iodoprotein compounds are also used: iodoferratin, iodolecin, iodotropone. - Jodglidin, Jodglidin, a compound of I. (10%) with vegetable protein, a dark brown powder; given in tablets (0.05 I.) two to six times a day after meals.-Jodipinum, Jodipinum, a compound of I. and sesame oil, a light yellow oily liquid; the drug is sold in two strengths-with 10% and 25% I.; even with long storage it does not decompose, when taken internally part of the jodipin is eliminated with the feces, part decomposes in the intestines with the release of I., and the larger part is absorbed, decomposed and excreted in the urine in the form of iodides; with subcutaneous injection jodipin remains at the injection site for a long time and gradually enters the circulation in small doses, consequently it remains in the body for a long time and has a prolonged moderate action, usually not causing iodism. It is indicated in all cases where KJ is used. Jodipin is also used as a diagnostic agent for determining the motor ability of the stomach and the secretory ability of the pancreas and liver. Internally 10% jodipin is given by the tablespoonful 2-3 times a day. For subcutaneous injections-10 cm³ of 10% jodipin 1 - 2 times a day or 10 cm³ of 25% jodipin; for enema 100-200 cm³ of 10% jodipin with 200.0 olive oil; jodipin has been used for radioscopy of the spinal canal, injecting 2 cm³ of 20% jodipin under the dura mater, and for bronchography, injecting 20-60 cm³ of 20% jodipin intratracheally; recently it has been used in urology, introducing jodipin as a contrast medium by means of a catheter into the renal pelvis.-Jodisan, Jodisan, a 20% solution of hexamethyldiamino-isopropanol-diiodide with 0.118 I. in 1 cc³. Used in bronchial asthma, syphilis of the brain, angina pectoris, subcutaneously or intravenously 1-2 cm³; sold in ampoules. - Jodival, Jodival, alpha-iod-isovaleryl-urea (CH₃)₂CH.CHJ.CO.NH.CO.NH₂, a white crystalline powder of bitter taste, difficult to dissolve in cold water, easily in hot water and alcohol. Contains 44% iodine; used instead of iodides; has a sedative effect. Dose 0.3 per dose. - Jodol, Jodol, tetraiodopyrrole, C₄J₄NH, a derivative of pyrrole, a loose, light yellow or yellow-brown crystalline powder without odor and color; almost insoluble in water (1:5,000), dissolves in 20% alcohol 1:15, easily in strong alcohol; when heated to 140-150°, without melting, it volatilizes, turning into iodine vapor; in solutions when heated above 40° it decomposes, releasing I. It has an antiseptic action; used externally instead of iodoform-in powder and in the form of ointment; internally very rarely-in tablets of 0.25; less poisonous than iodoform; excreted in urine in the form of iodides. A 10% solution of jodol in collodium forms the preparation Jodolcollodium, used for smearing. A mixture of jodol with 1% mentol is known under the name Jodolmenthol and is used in angina pectoris.-Jodopyrin, Jodopyrin, iodophenyl-dimethyl-pyrazolone, C_nH_nJON₂, or monoiodo-antipyrin, brilliant colorless needle-shaped crystals, melting at t° 160°; difficult to dissolve in water; contains 40% iodine. I. and antipyrin act, causing more significant anesthetic and antipyretic action. Used in tbc, typhoid, asthma and tertiary syphilis 0.5-1.0 per dose as an antiseptic and antineuralgic agent. - Jodostarin, Jodostarin, diiodostearic acid, Cj-H₃₁J_aCOOH, a delicate white crystalline powder with 47.5% iodine, without odor or taste, insoluble in water, dissolves in hot alcohol and fats. Absorbed in the intestines. Internally in powder and in tablets, 0.5 per dose, 2.0 per day. - Jothion, Jothion, diiodohydroxypropane, CH₂J.CH.(OH).CH_aJ, a slightly yellowish oily liquid of pleasant odor; dissolves in water 1:80, in glycerin-1:20; easily decomposes with the release of I. in an alkaline medium and when heated. Contains I. 79-80%; decomposes in light. It strongly cauterizes mucous membranes, therefore it is not given internally or subcutaneously; it is poisonous; used externally in oil or glycerin solution; through the skin up to 50% of the drug is absorbed, irritating the skin.

In ointments 1:2, 1:4 with fat - for tuberculous lymphomas, in late syphilis, for skin parasites, hair diseases, etc. - Lipoiodine, Lipojodin, di-iod-brassidic acid ethyl ester, CH₃(CH₂)₇C J=C J(CH₂)_nCOOC₂H₅ (Oswald), colorless, long, delicate needles or shiny flakes without color or odor; insoluble in water, very slightly soluble in alcohol, easily soluble in fatty oils. Contains I. 41.06%; decomposes in light, releasing I. Used internally 0.3 per dose one-three-five times a day after meals. - Sajodin, Sajodin, iodbehenic acid calcium (C₂₁H₄₂ JCOO)₂Ca, white, colorless and odorless powder, somewhat greasy to the touch, insoluble in water, very slightly soluble in alcohol. Contains 25% I. and 4.1% calcium. Decomposes and is absorbed in the intestines; does not cause iodism, is well tolerated even with long-term use, therefore it is readily used in severely ill patients: for apoplexy, asthma, angina pectoris, arteriosclerosis, tertiary syphilis, etc. Doses 0.5-1.0, two-four times a day. - Isoform, Isoform, a mixture in equal parts of paraiodanisole CH₃OC₆H₄J and calcium phosphate CaHPO₄ +2H₂O; powder in the form of shiny scales, insoluble in cold water and alcohol, soluble in hot water; explodes at 225°; used as an antiseptic and deodorant in the form of powder, in ointments, pastes; internally - for disinfection of the gastrointestinal tract. Local action of isoform is irritating. Single internal dose 0.5. - Tetrajodphenol-phthalein, a compound of I., similar to the corresponding compound of bromine (see), also called Jod-Tetragnost; in combination with sodium (Tetrajodphenolphthalein-Natrium) is used intravenously 3-3.5 in solution in 40 cm³ of warm water for cholecystography in cases of unclear disease of the gallbladder. The drug for the same purpose can be administered to ambulatory patients and per OS. V. Nikolaev. Discovery of iodine in forensic cases. Free iodine can be found only in fresh vomit (for example in poisonings with T-ha Jodi). In the presence of starchy substances (bread), the masses are colored blue. With yellow-brown discoloration of vomit, the addition of starch paste gives a blue color in the presence of I. In exceptional cases, free I. can be found by the same method and during preliminary examination of stomach contents. The easy absorption of I. by proteins and alkalis converts free I. into compounds. To detect absorbed I., vomit, parts of internal organs, etc. are treated with caustic soda and burned. The ash is extracted with water, the solution is filtered, concentrated to the smallest possible volume, a solution of sodium nitrite (NaNO₂-oxidizer) is added, acidified with dilute sulfuric acid, and shaken with chloroform. The latter in the presence of I. is colored violet. For quantitative determination, the ash filtrate after adding NaNO₂ and dilute sulfuric acid is heated, absorbing the released I. with starch paste. The resulting color is compared with standard solutions or the amount of I. is determined by titration with sodium thiosulfate. To detect I. in urine, 20-100 cm³ is acidified with dilute sulfuric acid, sodium nitrite is added and shaken with a minimal amount of chloroform: in the presence of I., chloroform is colored violet or pink (depending on the amount of iodine). In cases of small amounts of iodine, the urine is alkalized with caustic soda, evaporated, the resulting residue is calcined, and then proceeding as described in the examination of internal organs. Iodine in microscopic technique is used as a reagent for alkaloids, glycogen, starch, and cellulose. As a fixative, I. is used in the form of vapors, for which the object is suspended or lowered into a vessel with iodine vapor. Iodine vapor is sometimes used in fixing protozoa, for which a drop containing them is inverted over a vessel containing I. For fixing blood, it has been proposed to lower slides with blood smears into a vessel on the bottom of which is poured a mixture of I., formalin, and osmic acid (according to Werzberg; see Blood). For fixing tissues, the mixture of Dominichi (see Dominichi methods) containing I. is used. Solutions of I. in 70% alcohol, sometimes in mixture with KI (see Lugol's solution), are used in Gram staining, as well as for treating pieces fixed with mercurial mixtures, with the aim of removing insoluble Hg salts (carbonates and phosphates) by converting them into soluble iodides. Residual I. is then removed by washing in a 0.5% solution of sodium sulfite, as a result of which they are converted to NaI. By shaking amniotic fluid with crystals of I., the so-called iodine serum (Schulze; 1864) is obtained - a dark brownish-red liquid, which is used for maceration, diluting it before use with fresh serum to a light brownish color.