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.

     

A light and scanning-electron microscopic study of infection of tomato plants by virulent and avirulent races of Cladosporium fulvum

Infection of tomato plants byCladosporium fulvum Cooke was studied using light and scanning-electron microscopy. Races 1.2.3 and 4 ofCladosporium fulvum were used, whereas tomato cultivars, carrying the Cf2 gene (susceptible to race 1.2.3 and immune to race 4) and the Cf4 gene (immune to race 1.2.3 and susceptible to race 4) served as differentials. No differences were observed in growth between compatible and incompatible combinations during germination, subsequent formation of runner hyphae and stomatal penetration. Runner hyphae did not show directional growth towards stomata. Penetration usually occurred on the third or fourth day after inoculation. In compatible combinations the fungus grew intercellularly, often in close contact with spongy mesophyll cells. Under optimal conditions it did not cause visible damage to plant cells during early stages of infection. Under suboptimal conditions in winter, the host cells often reacted with callose deposition, but growth of the fungus did not appear to be inhibited. Ten to twelve days after inoculation conidiophores emerged through the stomata and produced conidia. In incompatible combinations fungal growth was arrested one to two days after penetration and confined to stomata and surrounding cells. Very soon the host cells, in contact with the fungus, deposited extensive amounts of callose. Later these cells turned brown and collapsed. At the surface of the host cells, contacted by fungal hyphae, abundant extracellular material could be observed by scanning-electron microscopy. Removing the epidermis of leaves before inoculation delayed the resistant response. On stripped leaves the rate of fungal growth was equal for both interactions up to ten days after inoculation, but the incompatible combination lacked sporulation.     

Determination of progesterone directly in milk fat as an improved method for fertility control in cattle

A simple and reliable method for the determination of progesterone in milk fat by radioimmunoassay has been developed. Application of the assay under field conditions has shown that all samples diagnosed " questionable" in the former milk progesterone test (MPT) could be characterized as positive or negative. Thus the total figure of animals daignosed correctly rose from 72.3% to 85.8%. The borderlines (ng progesterone / 10 mcl milk fat) set up for this assay were (1) pregnant and (1) nonpregnant (Day 20) and (.3) in estrus and (.3) not in estrus ( Day 0). Within the application for diagnosis of pregnancy, 81.4% were diagnosed correctly as pregnant while 96.3% were diagnosed correctly as not pregnant. The latter figure is somewhat lower than in the MPT (100%), but under the practical conditions the error lies within the range of false diagnosis due to problems with sample identification.     

Rotaviral antibodies in cow's milk.

In the past, it has been reported that neonatal diets made from unheated cow's milk were superior to those made from heated cow's milk. It was observed that piglets were equally protected from rotaviral diarrhea when they were fed diets made from either unheated milk that came from a cow immunized against porcine rotavirus or from a cow that was not immunized. Because of this observation, we examined four pools of "normal" cows' colostrum and 58 samples of "normal" cow's milk for the presence of antibody to rotavirus. All pools of colostrum, collected in four different years, had immunofluorescent antibody titers of 1:100 to rotavirus. Seventy-two percent of the samples of milk were also positive--titer no higher than 1:10. Antibodies to rotavirus were found in cow's milk at a creamery prior to but not after pasteurization. Rotaviral antibodies were detected in one out of eight brands of milk bought at the market--perhaps indicating inadequate pasteurization for this brand. These results support the proposition that, at least in part, unheated milk is superior to heated milk because unheated milk contains antibody to an ubiquitous enteropathogen like rotavirus.     

Bovine Cryptosporidiosis: Clinical and Pathological Findings in Forty-two Scouring Neonatal Calves

Cryptosporidia organisms were identified in 42 of 161 (26%) neonatal, diarrheic calves, over a 32 month period commencing July 1979. Forty of the 161 calves were submitted alive and cryptosporidiosis was diagnosed in 63% (25 of 40) of them. The cryptosporidia infected calves were usually one to two weeks old and came from 26 herds where the typical history was profuse, watery diarrhea in nearly all neonatal calves. The diarrhea usually started around one week of age, was unresponsive to all conventional antidiarrhea therapies, lasted for two or more weeks and was usually fatal. Twenty-nine (69%) of the cryptosporidia infected calves were submitted between December and February. These calves were often hutch reared.

Histopatholoical examination revealed large numbers of the coccidial parasite Cryptosporidium sp embedded in the microvilli of jejunal and ileal absorptive enterocytes of all affected calves. The organisms were identified as trophozoites and schizonts (asexual stages) and macrogametes (female sexual stages) with the electron microscope. Microgametes (male sexual stages) were not identified. Occasionally a merozoite (asexual stage) was also seen apparently burrowing into or about to be enveloped by a host microvillus. Observation of the organisms was much easier when diarrheic calves were submitted alive. Enterotoxigenic Escherichia coli were often cultured from intestines of dead calves and occasionally from calves submitted alive. Coronavirus particles were seen in one calf. In the last year of this study, oocysts were identified in fecal smears stained with May-Grünwald-Giemsa stain and fecal samples using a dichromate solution flotation technique.