This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
It has been previously noted that hydroperoxides resulting from the oxidation of mono- and polyunsaturated fatty acids are found normally in the organism, but peroxides appear only under abnormal conditions and particularly when abnormal fatty acids intervene. The manifestations of the type D offbalance in its oxygen phase thus can be attributed to the presence of peroxides. Biologically, the intervention of peroxides would be counteracted by peroxidases and catalases. It was interesting to study a clinical curiosity which could be connected with a probable intervention of peroxidases.
In several patients with frequent headaches, whose analyses showed a typical acid pain pattern, pain was repeatedly intensified or even induced by eating pears. No other fruit had such effect; some had the opposite effect. This led us to consider that the pain intensifying action was not due to an acid base change. The large amount of peroxidases in pears led us to isolate this enzyme in order to study its direct influence upon pain. Peroxidase could be obtained from pears in relatively small amounts, and showed reduced activity upon peroxides even in vitro. We were able to prepare much larger quantities of a highly active peroxidase from horse radish.
After being purified and tested for antiperoxide activity, preparations were administered orally to patients with acid or alkaline pain pattern. While the former was definitely intensified, there was no relief of the latter. It seemed that the effects obtained through the administration of isolated pexoridases were the same as those obtained when pears were eaten.
The relationship between fixation of oxygen and chlorides has led to the study of antioxidants capable of acting in situations of abnormal oxidation. It was hoped that these substances also would be able to influence the fixation of chloride ions.
We have utilized several groups of known antioxidants, starting with manganese compounds, such as inorganic salts, and later binding these to lipids. It is too early yet to draw any definite conclusions from animal experiments, and we have not used the compounds clinically. However, our studies up to now do not show any influence that could be interpreted as sufficient to warrant hope that these compounds can control the fixation of chlorides on fatty acids.
In the same series of researches, other antioxidants—some of them used for the preservation of edible fats and others for the control of oxidation in other substances such as rubber—were tried. We investigated the influence of tocopherols, the natural antioxidants for vegetable oils. Alpha tocopherol in doses of 100 mg. was administered several times a day to patients having symptoms and signs corresponding to an intervention of abnormal fatty acids. A decrease in the intensity of pain of an alkaline pattern was observed.
Along the same lines, we investigated the influence exerted by maleic acid, used to prevent the rancidity of edible fats. In proportion of 1 /10,000 this acid conserves these fats for months. Curiously enough, maleic and citraconic acid have shown an influence upon the abnormal manifestation of the type D.
For these reasons we utilized these two acids—maleic and citraconic— as anti D agents. In one study, the acids were injected intravenously in proportion of from 0.1 to 1 mgr./100 cc. of saline. In others, the sodium salts of the acid were used, while in still others the butyl esters were prepared and administered intramuscularly in oily solutions. For the present it is difficult to judge the effects obtained.
All the above mentioned attempts were made on the basis of a direct action upon fatty acids and other lipoidic constituents with negative polar groups which intervene in inducing offbalances. For the present, it seems that no single agent can resolve the problems that result from the plural intervention of various abnormal fatty acids at the different levels. The use of various agents acting selectively at the different levels involved seems to be the only available path by which therapeutic intervention against the multiple manifestations at different levels can be accomplished.
Before going further, we thought it useful to have a synoptic view of this special part of the pharmacological activity as obtained through the study of the influence upon pain and the systemic level analyses as seen in humans. To this we added the effect seen upon tumors in humans. Tables XX and XXI which give this information in a very condensed form, were limited to the most important agents tested for each group studied. The effects are indicated as clinical results also for the facility of the presentation.
Group | Agent | Systemic Level | Pain | Influences Exerted Upon Tumor |
Fatty Acids | Saturated | None | None | None |
Polyunsaturated | Slight | Fair | Some, not consistent, | |
not persistent | ||||
Mixtures from organs | " | Good | " " " | |
" from cod liver | " | Fair | Fair, not consistent, | |
oil | not persistent | |||
Irradiated | " | " | ||
Conjugated | " | " | i" | |
a—OH | None | None | None | |
Polyhydroxy | Slight | Slight | None | |
Chloro derivatives | Fair | Fair | Some, not consistent, | |
not persistent | ||||
Oleic | Slight | None | None | |
A Idehydes | Crotonic | Slight | Slight | Slight, not consistent, |
not persistent | ||||
Propionic | Good | Good | Fair | |
Heptylic | Good | Slight | Fair | |
Sulfur | Thiosulfates | Good | Good | Fair |
Compounds | S. Colloidal | None | None | None |
Mercaptans | Slight | Slight | Good, consistent, | |
persistent | ||||
Fair | Fair | Fair, not consistent, | ||
not persistent | ||||
Methyl thioglycolate | Slight | Fair | " " " | |
Tetrahydronaphtha- | Fair | Fair | Good, consistent | |
lene persulfides | and persistent | |||
Selenium | Alkyldiselenide | Fair | Slight | Good, consistent, |
Compounds | persistent | |||
Perselenide | Fair | Good | " " " | |
Peracids | Perborate | Fair | Fair | Some, not consistent, |
Perchlorate | not persistent | |||
Hormones | Testosterone | Slight | None | Seldom, not consist- |
ent, not persistent | ||||
Mustards | Fair | Fair | Fair, " | |
Hydrines | Epichlorohydrin | Fair to good | Slight | Fair, consistent, persistent |
Table XXI
Clinical Results With Agents That Act Upon The Offbalance Type "D"
Systemic | Influences Exerted | |||
Group | Agent | Level | Pain | Upon Tumor |
Sterols | Cholesterol | Fair | Fair | Seldom, not consist- |
ent, not persistent | ||||
Insapon. fraction | ||||
of organs | " | " | ||
of eggs | " | " | " | |
of milk | " | " | " | |
A liphatic saturated | " | |||
Good | Good | " | ||
Pentanol | Fair | Fair | Fair, " " | |
Heptanol | " | Slight | Good, consistent, per- | |
sistent | ||||
Octanol | Slight | 44 | Fair, not consistent, | |
not persistent | ||||
Octanediol | " | " | Slight | |
Nonanol | None | None | None | |
Polyalcohol | ||||
Slight | Good | Good, consistent, per- | ||
sistent | ||||
Inositol | None | None | None | |
Unsaturated | ||||
Oleic | Slight | Slight | None | |
Linoleic | " | None | ||
Polyunsaturated | " | Fair | Slight, not consistent. | |
not persistent | ||||
Polyconjugated | " | " | Fair, " " | |
Crotonic | " | Slight | " | |
Ricinoleic | " | Fair | Slight, " " | |
Salicylic | Slight | Fair, " " | ||
Hormones | Estrogens | " | I" | Slight, " " |
Amines | Aminobutanol | " | Fair | " |
Hexylamine | " | " | ||
Heptylamine | Good | " | Fair, " " | |
Glucosamine | Good | Slight | None | |
Nicotinic | ||||
acid deriv. | Niketamide | " | Good | None |
Metals | Iron | Fair | Slight | None |
None | ||||
Bismuth | " | " | ||
Halogen | Slight | Fair | " | |
Oxygen | None | Good | None |
 
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