The effect of protamine derivatives on calcium metabolism in patients with malignancy.

Anderson, J.; Tomlinson, R. W. S.; Wright, James E.

doi:10.1038/bjc.1967.7

Cited by 10 publications

(5 citation statements)

References 13 publications

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“…Prolothan A which is not active against heparin has no such effect on serum calcium. This side effect has been reported in more detail (Anderson, Tomlinson and Wright (1967) O'Meara (1961) showed that protamine neutralised this factor and Thornes and Martin (1961) using Hela cell mono-layers showed protamine to have both growth arresting and cyto-pathic effects. These effects were confirmed in experimental mice tumours (Muggleton, MacLaren and Dyke, 1964).…”

Section: Side Effectsmentioning

confidence: 63%

Clinical trial of protamine in the treatment of malignant diseases

Wright¹

1968

Br J Cancer

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PROTAMINE was first used in the treatment of malignant disease by O'Meara and O'Halloran (1963) and Hughes (1964). In a small series of cases they reported that changes occurred in over half the patients treated, malignant masses becoming smaller and more mobile, and malignant ulcers re-epithelialising. This larger clinical trial was undertaken to confirm their results, and to assess the value of protamine as a cancer chemotherapeutic agent. MATERLALS AND METHODSThe protamine used in this trial was Clupeine prepared from herring roes. It is inactive if given orally, and must therefore be used parenterally. Protamine itself as the salt yields a strongly acidic solution unsuitable for use over long periods. Three other forms were available. Prolothan G is a 10 % solution of protamine in 40 % glucose, brought to neutrality. It is the most potent form available, being fully active as measured by heparin titration. However, it is still too irritative for intramuscular use and was given in doses of 1-2 g. daily (10-20 c.c.) diluted in 1 1. of normal saline by slow intravenous infusion. Prolothan A is a 10 % solution of protamine formaldehyde bi-sulphite. It has no activity as measured by heparin titration, but is thought to break down in the body to yield active protamine. It was administered in doses of 2 g. daily (20 c.c.) by deep intramuscular injection in divided doses. The third form was a cream containing 10 % protamine in a lanolin base. Case selectionA total of 56 cases was treated. With few exceptions these were either unsuitable for treatment by conventional methods of had failed to respond to previous therapy. Terminal patients were excluded. Only cases where the tumour mass or ulcer was measurable directly or by radiography were accepted. A few cases with specific symptoms were also accepted where subjective assessment was possible. Histological proof of diagnosis was obtained in all but one case. In this instance clinical diagnosis was thought to be incontrovertible. Scheme of treatmentSeventeen cases with malignant ulcers were treated with protamine cream. This was applied twice daily for a minimum of 1 month. The size of the ulcer was measured weekly. Thirty-nine cases with solid tumours were treated. Twenty-one

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Section: Side Effectsmentioning

confidence: 63%

Clinical trial of protamine in the treatment of malignant diseases

Wright¹

1968

Br J Cancer

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“…The authors suggested that protamine was rapidly removed frotn the blood, or that it was quickly bound to some constituent of the blood. JOHNSTON et al reported that protamine produced hypophosphatemia in normal rats and ANDERSON et al (1967) obtained very irregular changes in man. In the present study there were great variations in the serum levels of inorganic phosphorus.…”

Section: Resultsmentioning

confidence: 99%

The Hypocalcemic Effect of Protamine in Goats and Sheep

Luthman¹,

Jonson²,

Persson³

2010

Zentralblatt Für Veterinärmedizin Reihe A

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Zusammenfassung Der hypokalzämische Effekt von Protamin bei Ziegen und Schafen Protamin als Antagonist des Heparins induziert offensichtlich Hypokalzämie durch Verhinderung von Knochenresorption. In der vorliegenden Studie wurde der hypokalzämische Effekt von Protamin bei jugendlichen und erwachsenen Tieren verglichen. Hypokalzämie tritt auf bei Lämmern und laktierende Ziegen, nicht aber in nicht laktierenden Mutterschafen. Der Serum‐Kalzium‐Gehalt änderte sich nicht, wenn Heparin 5 Minuten vor Protamin gegeben wurde. Protamin reduzierte auch das Anwachsen des Serum‐Kalziums nach EGTA‐induzierter Hypokalzämie. Résumé L'effet hypocalcémique de la protamine sur les béliers et moutons Il y a preuve que la protamine, antagoniste de l'héparine, provoque l'hypocalcémie par une inhibition de la résorption de l'os. Au cours de la présente étude, l'effet hypocalcémique de la protamine sur des animaux en bas age a été comparé a celui produit sur des animaux adultes. L'hypocalcémie s'est déclarée chez les agneaux et les béliers en lactation mais pas chez les brebis non‐lactantes. Le sérum de calcium n'était pas modifié lorsque l'héparine était administrée cinq minutes avant la protamine. De meme, la protamine réduit l'augmentation en sérum de calcium après une hypocalcémie provoquée par EGTA. Resumen El efecto hipocalcémico de la protamina en cabras y ovejas Existe la evidencia de que el adversario de la heparina la protamina induce hipocalcemia impidiendo resorpción del hueso. En el presente estudio el efecto hipocalcémico de la protamina fué comparado en animales jóvenes y adultos. Hipocalcemia ocurrió en corderos y cabritos lactantes, pero no en ovejas no lactantes. Suero de calcio no hizo ningún cambio cuando la heparina fué dada cinco minutos antes de la protamina. La protamina también redujo el incremento en suero de calcio después de EGTA‐inducción de hipocalcemia.

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“…Earlier reports of the hypocalcemic effect of protamine [4][5][6], including a detailed study of actions of protamine in vivo and in vitro which pointed to a locus of action on bone [7], indicated a variable hypocalcemic response (4-6) or an effect limited to a maximum fall of 2-3 mg/dl in calcium concentration [7]. The overwhelming of calcium homeostatic mechanisms resulting in fatal hypocalcemia that we found in rats deprived of calcium in their diet, where bone turnover is high, was not previously reported.…”

Section: Discussionmentioning

confidence: 98%

Protamine: A powerfulin vivo inhibitor of bone resorption

et al. 1984

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Protamine is shown to be a powerful disrupter of calcium homeostasis, acutely inducing a severe hypocalcemia in both rabbits and rats. The magnitude of its effect correlates with bone turnover. Protamine does not significantly alter the renal excretion of calcium, and is effective whether or not there is calcium present in the gut. Protamine causes a significant fall in the specific activity of 45Ca in the blood in animals whose bone has been prelabeled with 45Ca. These data suggest that protamine induces hypocalcemia by blocking calcium efflux from bone. Further work seems indicated to define the biochemical mechanism of this action.

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The effect of protamine derivatives on calcium metabolism in patients with malignancy.

Cited by 10 publications

References 13 publications

Clinical trial of protamine in the treatment of malignant diseases

Clinical trial of protamine in the treatment of malignant diseases

The Hypocalcemic Effect of Protamine in Goats and Sheep

Protamine: A powerfulin vivo inhibitor of bone resorption

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