The use of vitamin D metabolites and analogues for the prevention of milk fever in dairy cattle

During the past decade it has been discovered that vitamin D₃ (cholecalciferol) is converted into 25-hydroxycholecalciferol in the liver and that this compound in converted in the kidney into 1, 25-dihydroxycholecalciferol. These metabolites and particularly 1, 25-dihydroxycholecalciferol, rather than vitamin D itself, have powerful effects on calcium metabolism, stimulating the absorption of calcium from the gastrointestinal tract and the resorption of calcium from bone. A synthetic analogue of these metabolites, 1-hydroxycholecalciferol, is rapidly converted in the liver into 1, 25-dihycroxycholecalciferol. Thus the two metabolites and the synthetic analogue may be valuable for the prevention on treatment of milk fever.The three compounds, when administered in doses ranging from 0.5 to 32g/kg bodyweight increase the concentrations of calcium and phosphorus in the blood plasma of cattle more quickly than much larger doses of vitamin D₃. Their principal effect is to stimulate the absorption of calcium from the gastrointestinal tract. At the same time they decrease the plasma concentration of magnesium slightly. Trials of 25-hydroxycholecalciferol and 1-hydroxycholecalciferol in the prevention of milk fever have shown promising results.

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Kurzfassung Im vergangenen Jahrzehnt hat man festgestellt, dass das Vitamin D₃ (Cholecalciferol) in der Leber in 25-Hydroxycholecalciferol umgewandelt wird und die Nieren diese Verbindung wiederum in 1, 25-Dihydroxycholecalciferol umbilden. Mehr noch als Vitamin D selbst zeigen diese Metaboliten und hier insbesondere das 1, 25-Dihydroxychlecalciferol umfangreiche Auswirkungen auf den Kalziummetabolismus, indem sie die Kalziumabsorption aus dem Magen-Darmtrakt und die Kalziumresorption der Knochen anregen. Ein synthetischer Analogstoff zu diesen Metaboliten, das 1- Hydroxycholecalciferol, wird in der Leber rasch in 1, 25-Dihydroxycholecalciferol umgewandelt. Die beiden Metaboliten und der synthetische Analogwirkstoff könnten daher für die Milchfieberprophylaxe bzw-therapie von Nutzen sein.Werden die drei Verbindungen in Dosen von 0,5 bis 32g/kg Körpergewicht verabreicht, so erhöht sich die Kalzium-und Phosphorkonzentration im Blutplasma der Kühe schneller als bei bedeutend höheren Dosen von Vitamin D₃. Ihre Hauptwirkung liegt in der Anregung der Kalzium-absorption aus dem Magen-Darmtrakt. Gleichzeitig bauen sie jedoch auch in geringfügigem masse die Magnesiumkonzentration im Plasma ab. Versuche mit 25-Hydroxycholecalciferol und 1-Hydroxycholecalciferol haben bei der Milchfieberprophylaxe vielversprechende Ergebnisse gezeigt.

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Resume Au cours de la dernière décennie, on a découvert que la vitamine D₃ (cholécalciférol) se transformait en 25-hydroxycholécalciférol dans le foie et que ce composé se transformait en 1, 25-dihydroxy-cholécalciférol dans le rein. Ces métabolites, et en particulier le 1, 25-dihydroxycholécalciférol, ont, plus que la vitamine D elle-même, des effets puissants sur le métabolisme du calcium: ils stimulent l'absorption du calcium de l'appareil gastrointestinal et la résorption du calcium des os. Une substance homologue synthétique de cés metabolites, le 1-hydroxycholécalciférol, se transforme rapidement en 1, 25-dihydroxycholécalciférol dans le foie. Les deux métabolites et la substance homologue synthétique peuvent donc s'avérer précieux dans la prévention ou le traitement de la fièvre laiteuse.Administrés en doses allant de 0,5 à 32g/kg de poids corporel, ces trois composés augmentent les concentrations de calcium et de phosphore dans le plasma sanguin du bétail plus rapidement que des doses beaucoup plus fortes de vitamine D₃. Ils ont pour principal effet de stimuler l'absorption du calcium de l'appareil gastro-intestinal. Simultanément, ils réduisent légèrement la concentration de magnésium dans le plasma. Les essais d'utilisation du 25-hydroxycholécalciférol et du 1-hydroxycholécalciférol pour la prévention de la fièvre laiteuse ont donné des résultats prometteurs.

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Riassunto Nel corso dell'ultimo decennio si è scoperto che la vitamina D₃ (colecalciferolo) viene trasformata nel fegato in 25-idrossicolecalciferolo, il quale, a sua volta, si trasforma nel rene in 1, 25-diidrossicolecalciferolo. Detti metaboliti, ed in specie l'1, 25-diidrossicolecalciferolo., più che la stessa vitamina D, hanno potenti effetti sul metabolismo del calcio, poichè ne stimolano l'assorbimento da parte dell' apparato digerente e l'anabolizzazione da parte delle ossa. Un composto sintetico analogo di questi metobiliti, l'1, idrossicolecalciferolo, viene rapidamente trasformato nel fegato in 1, 25-diidrossicolecalciferolo. Perciò i due metaboliti e il composto sintetico analogo possono essere utili per la profilassi e la cura della febbre da latte.I tre composti, se somministrati in dosi da 0.5 a 32g/kg peso corporeo, aumentano la concentrazione del calcio e del fosforo nel plasma sanguigno del bestiame più rapidamente di dosi molto maggiori di vitamina D₃. Il loro effetto principale è quello di stimolare l'assorbimento del calcio da parte dell'apparato digerente. Contemporaneamente, essi riducono leggermente la concentrazione di magnesio nel plasma. Esperimenti con il 25-idrossicolecalciferolo nella profilassi della febbre da latte hanno dato risultati promettenti.

     

Intussusception following renal transplantation in dogs (author's transl)]

In a consecutive and non-selected study of 54 kidney transplanted dogs, 12 cases of intussusception of the small intestine developed in 8 dogs. The patogenesis is still unknown. It has been postulated that the time of the operation (4--7 hours) and the segmental termination of the post-operative atony in the intestine are essential factors in this fatal complication. The last 16 dogs in this material were peroperatively treated with antikolinergics (Mestinon NFN), which was continued until normal function of the intestine. In these dogs there were no evidence of intussusception. The value of this profylaxis is open to discussion and it is essential to solve the problem of intussusception through a "blind" and controlled trial.