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Arsenic MOA

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The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

LEAD STUDIES : III. THE EFFECTS OF LEAD ON RED BLOOD CELLS. PART 1. CHANGES IN HEMOLYSIS

Authors: Aub, JC; Reznikoff, P; Smith, DE (1924) Journal of Experimental Medicine 40:151-172. HERO ID: 1027354

[Less] It appears, from the investigations in other laboratories, that the anemia observed in cases of lead . . . [More] It appears, from the investigations in other laboratories, that the anemia observed in cases of lead poisoning is due to destruction of blood rather than to diminished production of blood. The method of poisoning cells in vitro with lead was adopted in order to study this phenomenon, and distinct effects were thereby obtained, even when only 0.001 mg. of lead is added to approximately 5 billion washed red corpuscles. In order to obtain optimum results the usual dosage employed was ten times this or 0.01 mg. per 5 billion cells. The following changes were observed in cells so treated. 1. Such a marked increase in the resistance to hypotonic salt solution develops that complete hemolysis does not occur until the cells are exposed to a saline solution of 0.05 per cent. Untreated cells are completely hemolyzed in 0.25 or 0.225 per cent saline. 2. This reaction is quantitative and varies with the concentration of lead used. Under the conditions of our experiments this phenomenon seems to be unique. The effects of arsenic are very slight in comparison. 3. While from this reaction it may be concluded that lead increases cellular resistance, it also appears that it shortens the life of blood cells. This may be demonstrated by the much more rapid appearance of hemolysis than normal when the cells are merely allowed to stand in Ringer solution of any dilution. 4. In rabbits with acute lead poisoning these same phenomena may be noted in vivo. 5. Both phenomena may be changed in vitro by varying the time and temperature of the reaction and the concentration of lead, as Fici has already pointed out. 6. If normal cells stand in Ringer solution for 6 hours something diffuses into the solution which largely reduces the action of lead. After repeated washing these cells react with lead in the usual manner. 7. Small amounts of serum react with lead and eliminate its effects. Red blood cells, treated with a mixture of lead and blood serum, show normal hemolysis in hypotonic salt solution. 8. When lead is added to whole blood the only evidence of this neutralization is a marked decrease in the intensity of the reaction. This is probably explained by the fact that since both serum and cells are present together, the lead reacts with both simultaneously. This in turn explains how the reaction may occur in vivo. 9. The change in hemolysis does not appear in the blood of all species of animals. In the species in which it does occur, anemia and stippling of the red cells also tend to develop readily during lead intoxication. 10. In vitro, cells which have been exposed to lead are far more fragile than normal blood cells. Slight trauma causes them to hemolyze. In vivo this is probably an important causal factor in the increased destruction of blood and in the anemia of acute lead poisoning. 11. The serum of a rabbit which has been immunized to human blood, causes more rapid and complete hemolysis in cells treated with lead than in the control cells. No satisfactory explanation for this has been found.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The Effect of Acetaldehyde and Methylene Blue on the Fermentation of Glucose and Fructose by Yeast-Juice and Zymin in presence of Phosphate and Arsenate

Authors: Harden, A; Henley, FR (1921) Biochemical Journal 15:175-185. HERO ID: 1252100


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Report of Fifty-Eight Cases of delayed Arsenical Poisoning, following the Administration of "606" Preparations

Authors: Strathy, GS; Smith, CH; Hannah, B (1920) HERO ID: 1382124


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

EXPERIMENTAL ACUTE NEPHRITIS : A STUDY OF THE ACIDOSIS, NITROGEN AND CHLORIDE RETENTION, AND OF THE PROTECTIVE ACTION OF SODIUM BICARBONATE

Author: Goto, K (1918) Journal of Experimental Medicine 27:413-424. HERO ID: 1027364

[Less] 1. In experimental nephritis caused by cantharidin, arsenic, diphtheria toxin, and potassium chromate, . . . [More] 1. In experimental nephritis caused by cantharidin, arsenic, diphtheria toxin, and potassium chromate, in addition to the retention of the non-protein and urea nitrogen and of the chlorides in blood, an acidosis occurs. 2. Sodium bicarbonate given by the stomach has the power of diminishing the acidosis in these types of nephritis. 3. The degree of increase in the non-protein and urea nitrogen content in the blood in mild nephritis varies considerably in different dogs receiving the same dose per kilo of a given poison. 4. Histological examination shows little if any influence resulting from the administration of sodium bicarbonate upon the grade of the nephritis induced by the poisons.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

THE RESISTANCE OF SPIROCHETES TO THE ACTION OF HEXAMETHYLENETETRAMINE DERIVATIVES AND MERCURIAL AND ARSENIC COMPOUNDS

Author: Akatsu, S (1917) Journal of Experimental Medicine 25:363-373. HERO ID: 1027367

[Less] The majority of the 76 new compounds possessed spirocheticidal powers ranging between 1: 1,000 (30) . . . [More] The majority of the 76 new compounds possessed spirocheticidal powers ranging between 1: 1,000 (30) to 1:2,500 (14), while only 2 attained the power of 1:5,000, 1 of 1: 25,000, and 2 of 1: 50,000. On the other hand, 8 killed the spirochetes in a dilution of 1: 750, 10 in 1:500, 7 in 1:250. 1 in 1: 100, and 1 in 1:50. It may be mentioned that the 2 (M1, M4) of 1:50,000 and 1 (M7) of 1:25,000 belong to the mercury compounds, and that mercuric chloride kills the organisms in a dilution of 1: 100,000 under the same experimental conditions. It is also interesting to compare some of the more common chemicals and therapeutic reagents. Phenol is spirocheticidal in a dilution of 1: 2,500, lysol in 1: 5,000, formalin in 1: 750, salvarsan in 1: 7,500, and neosalvarsan in 1: 2,500. Thus, of the new compounds there are at least 14 which have the same spirocheticidal power in vitro as has neosalvarsan. It is of interest to note that nine compounds possessing the 1:1,000 spirocheticidal power showed only one-tenth of the antiseptic action when tested upon Bacillus dysenteriae and Streptococcus, while some showed an even greater difference in this respect. Nos. 16, 21, 29, 218, and 244 were effective in a dilution of 1:2,500 for spirochetes and in a 1:100 or lower dilution for the bacteria just referred to. Preparations 46 and 84 appear to exert about the same effect both on the spirochetes and the bacteria, neither being very strong. Atoxyl killed the spirochetes in a 1:50 dilution. One of the most striking results was obtained with various hemolytic substances. Neufeld and von Prowazek found that spirochetes, unlike bacteria in general, are highly susceptible to the lytic action of sodium taurocholate and saponin, and they considered that this phenomenon was of differential diagnostic value in determining plant and animal organisms. Their observations were confirmed by Gonder, who found, however, that spirochetes, especially treponemata, offer a great deal of resistance at the beginning, but finally undergo lysis, with their cell bodies swollen up or macerated. In the present experiment we have found that these substances not only bring about cytolysis of the spirochetes in higher concentrations, but also kill them without causing a gross destruction of the cells in very high dilutions; thus, sodium cholate in 1: 5,000, sodium glycocholate and taurocholate in 1: 2,500 each, saponin in 1:7,500. Sodium oleate, one of the most powerful hemolytic agents killed the spirochetes in 1: 7,000, and cobra lecithide and native cobra venom in a dilution of 1:1,000 each. Neither sodium nor potassium iodide displayed any marked spirocheticidal property (1: 10 only), while iodine in the form of Lugol's solution was able to kill them at 1:75.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

CHEMOPATHOLOGICAL STUDIES WITH COMPOUNDS OF ARSENIC : IV. THE CHARACTER AND DISTRIBUTION OF RENAL INJURY PRODUCED BY ARSENICALS AS INDICATED BY THE PROCESSES OF REPAIR

Authors: Pearce, L; Brown, WH (1916) Journal of Experimental Medicine 23:443-459. HERO ID: 1027371

[Less] 1. The processes of repair in the kidneys of guinea pigs after sublethal doses of certain arsenical . . . [More] 1. The processes of repair in the kidneys of guinea pigs after sublethal doses of certain arsenical compounds indicate that all arsenicals do not produce a purely vascular type of renal injury. 2. While some arsenicals produce a predominantly vascular injury and others produce a predominantly tubular injury, both these tissue elements are undoubtedly always affected, although in varying proportion. In addition, the interstitial connective tissue is probably always affected. The diffuse proliferation of this tissue may be relatively conspicuous in the processes of repair after arsenicals that cause but slight vascular injury. 3. All red kidneys do not necessarily show identical pictures during the processes of repair; the same is true of pale kidneys. 4. The mode of action of an arsenical compound as a renal toxic agent is bound up with the chemical constitution of the compound.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

CHEMOPATHOLOGICAL STUDIES WITH COMPOUNDS OF ARSENIC : III. ON THE PATHOLOGICAL ACTION OF ARSENICALS ON THE ADRENALS

Authors: Brown, WH; Pearce, L (1915) Journal of Experimental Medicine 22:535-543. HERO ID: 1027372

[Less] 1. Toxic doses of all arsenicals of which we have any knowledge produce definite pathological changes . . . [More] 1. Toxic doses of all arsenicals of which we have any knowledge produce definite pathological changes in the adrenals of guinea pigs. These changes include congestion, hemorrhage, disturbances in the lipoid content, cellular degenerations and necroses, and reduction in the chromaffin content. 2. The character and severity of the injury produced by different arsenicals varies with the chemical constitution of the compounds. 3. From these facts, we believe that adrenal injury is an important factor in arsenical intoxication and suggest that therapeutic doses of some arsenicals may produce adrenal stimulation.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

A FURTHER STUDY OF NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE NEPHRITIS

Authors: Karsner, HT; Denis, W (1914) Journal of Experimental Medicine 19:259-269. HERO ID: 1027382

[Less] These studies, like all studies of the kidney, are difficult of interpretation because of the impossibility . . . [More] These studies, like all studies of the kidney, are difficult of interpretation because of the impossibility of producing a pure glomerular or pure tubular nephritis. Arsenic nephritis in its early stage is physiologically a vascular nephritis, but anatomically tubular, and shows in this stage almost no retention of nitrogen, although studies of urinary nitrogen indicate an increased catabolism. On the other hand, diphtheria nephritis in the early stages is anatomically a nephritis with marked involvement of the glomerulus anatomically, but it is physiologically a tubular form, and in this early stage there is little or no nitrogen retention although studies of metabolism indicate that protein catabolism is increased by the administration of diphtheria toxin. In both cases, however, there appears to come a time when the excreting power of the kidney is exhausted and nitrogen accumulation occurs in the blood. This is much less marked in the arsenic nephritis, with less tubular change, than in diphtheria toxin nephritis with its marked tubular degeneration. This same late accumulation of blood nitrogen is seen in immune serum nephritis, where the tubular changes are persistent and relatively more severe than the glomerular change. It might well be said that this is no argument for the influence of the tubules in the excretion of waste nitrogen because of the general exhaustion of the organism as a whole and of the kidney in particular, and that no positive conclusions can be drawn is indicated by the opening sentence of this summary. Tartrate nephritis was at first considered as purely tubular; but the appearance of occasional glomerular change, as mentioned by Wells in one of his animals, and the fact that the presence of precipitated albumen in the subcapsular space, pointed out by Pearce and Ringer, probably indicates an increased permeability of the tuft capillaries, all lead to the conclusion that although the tubular change predominates, there is, possibly, slight alteration of the glomerulus. This form of nephritis shows the most marked retention of nitrogen, persisting even though the glomeruli show almost no change, tending to clear up with the progress of time and evidently also with the repair of the tubular change, and bearing a direct relation to the dose of tartaric acid and presumably with the degree of tubular change. It must be remembered, however, that the nephritis in the cases of greatest retention is a very severe form, and this again clouds the physiological interpretation of the results. The study shows no reason for altering the conclusions of our earlier studies, but from the interpretation accorded above it appears to throw more stress on tubular change as determining nitrogen retention. It confirms in addition the value of the methods used for studies of this type.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

EXPERIMENTAL STUDIES ON THE ADMINISTRATION OF SALVARSAN BY MOUTH TO ANIMALS AND MAN

Authors: Kolmer, JA; Schamberg, JF (1912) Journal of Experimental Medicine 15:498-509. HERO ID: 1027391

[Less] Salvarsan in capsule and in solution in doses varying from 0.1 to 0.6 of a gram was administered by . . . [More] Salvarsan in capsule and in solution in doses varying from 0.1 to 0.6 of a gram was administered by mouth to seven patients suffering from syphilis. Five patients were given full doses of 0.6 of a gram. One patient (case 3) received in the aggregate within four weeks 2.4 grams without loss of weight or any disturbing effects. An ulcerating gumma of the knee was practically healed after a period of five weeks. This was the only patient of the seven, however, in whom notable improvement in the cutaneous manifestations followed the administration of the drug. This ulceration would probably have healed as soon, or possibly sooner, under the influence of mercury and the iodids. From the above observations, it would appear that salvarsan administered by mouth up to the full dose of 0.6 of a gram, has a perceptible though feeble therapeutic effect on cutaneous syphilitic manifestations. We should naturally expect the influence of any drug to be more evident in the case of a gumma, in which spirochaetes are only sparsely present, than in the secondary syphilides in which the spirochaetes are present in enormous numbers. Cutaneous gummata are readily healed at times by very small doses of mercury or iodids. It is interesting to note that the administration of the full dose of the drug by mouth does not appear to give rise to symptoms of systemic arsenical poisoning, unless the vomiting and diarrhea be regarded as such. After some of the full dose administrations, there was neither vomiting nor diarrhea. As salvarsan contains 34 per cent. of arsenic, these patients received the equivalent of five grains of arsenic. In case 3, in the course of four weeks the patient took by mouth the equivalent of over twelve grains of arsenic, without vomiting or having diarrhea, and with no loss of weight or disturbance of health. The urine of this patient was entirely normal. It would seem, therefore, that salvarsan is not converted in the gastro-intestinal tract into an organotropic arsenical compound, and it is possible that it may remain practically unchanged.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

THE SIGNIFICANCE OF LEAD ARSENATE COMPOSITION

Author: Volck, WH (1911) Science 33:866-870. HERO ID: 1252101