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Plasma 1,25-dihydroxyvitamin D and parathyroid hormone levels in paretic dairy cows
Abstract
Parathyroid hormone, 1,25-dihydroxyvitamin D, calcium, and phosphorus were determined in the plasma of 12 cows during the period immediately prior to, during, and after parturition. Eight were aged cows (≥ third lactation), and four considered as young cows (≤ second lactation). Four aged cows developed severe hypocalcemia (4.95 ± 1.1 mg/100 ml plasma) accompanied by paresis, whereas the four nonparetic aged cows experienced only mild hypocalcemia (8.43 ± 0.23 mg/100 ml plasma) at parturition. The mean ± SE plasma calcium value for the young cows was 9.02 ± 0.17 mg/100 ml at parturition. Development of severe hypocalcemia in the paretic cows was associated with increased plasma parathyroid hormone, 1,25-dihydroxyvitamin D, and a decrease in plasma phosphorus. Plasma calcium and phosphorus were negatively correlated (within cow) with the increase in parathyroid hormone (r = -0.57, r = -0.38) and the increase in plasma 1,25-dihydroxyvitamin D (r = 0.58, r = -0.34). Parathyroid hormone was positively correlated with the increased 1,25-dihydroxyvitamin D levels (r = 0.31). These observations would suggest that the development of hypocalcemia at parturition in dairy cows was not due to failure of adequate 1,25-dihydroxyvitamin D.
... Parturient paresis is characterized by failure to maintain normal calcium in blood plasma, thus resulting in hypocalcemia and loss of neuromuscular coordination (9). Development of severe hypocalcemia in aged dairy cows is associated with increases of parathyroid hormone, 1,25-dihydroxyvitamin D, and decrease in phosphorus in plasma (7). Horst et al. (8) also reported that 24,25-dihydroxyvitamin D [24,25(OH)2D] concentrations in plasma were elevated above baseline precalving in cows that became paretic around calving. ...
... On days 1 and 3 postpartum, plasma Ca of paretic treated cows was lower, but not significantly (P>.05), compared to controls. Changes of P concentrations in plasma precalving and postcalving ( Table 2) were similar to (1,6,7,9). a'bMeans in same row followed by different superscripts differ (P<.05). ...
... The authors suggested that 24,25(OH)2D may play a role in the pathogenesis of parturient paresis. Horst et al. (7) found increased 24,25(OH)2D concentrations precalving in cows that developed parturient paresis; no difference was found, however, on the day of calving between paretic and nonparetic cows. In the experiment herein reported there was little if any relationship between plasma 24,25(OH)2D and Ca concentrations in the treated paretic cows. ...
Fifty percent (7/14) of aged cows treated with 4 mg 24,25-dihydroxyvitamin D3 intramuscularly precalving developed parturient paresis shortly after calving compared with 7% (1/14) of controls. Injection of 24,25-dihydroxyvitamin D3 increased concentrations in blood plasma 15 times that in control cows. Blood plasma 1,25-dihydroxyvitamin D concentrations were elevated in all groups on day of calving but were not different. Injection of 24,25-dihydroxyvitamin D3 did not alter the typical plasma profile for calcium, phosphorus, or 1,25-dihydroxyvitamin D of paretic or nonparetic cows around parturition. Although injection of 24,25-dihydroxyvitamin D3 was associated with an increased incidence of parturient paresis, the mechanism remains unknown.
... Why then was rumen calcium absorption capacity decreased in cows that developed parturient paresis when the concentration of 1,25(OH) 2 D in blood plasma was significantly higher than in cows showing no abnormality? Higher circulating 1,25(OH) 2 D levels in cows with parturient paresis, compared with those without severe hypocalcemia, have been reported by others (Horst et al., 1978;Horst and Reinhardt, 1983). However, this is not always seen and some cows with marked hypocalcemia may not have elevated blood levels of 1,25(OH) 2 D (Rodríguez et al., 2016). ...
... This and a decrease in serum tartrate-resistant acid phosphatase indicate that mobilization of calcium from bone by the activity of osteoclasts is depressed in cows with parturient paresis (Lappeteläinen et al., 1993;Kurosaki et al., 2007). It has been suggested that although the blood plasma concentration of 1,25(OH) 2 D and PTH are higher in cows with parturient paresis than in those without clinical signs of hypocalcemia (Horst et al., 1978;Horst and Reinhardt, 1983), bone cell mobilization of calcium in response to PTH may be blunted in cows susceptible to parturient paresis (Goff et al., 2014). Feeding anionic salts prepartum decreases the risk of parturient paresis in dairy cows but the consequent slight systemic acidosis does not, by itself, lead to increased mobilization of calcium from bone (Liesegang et al., 2007). ...
Absorption of dietary calcium from the rumen is a quantitatively important process in calcium homeostasis of ruminants. In 3 separate experiments in dairy cows, we applied a technique developed in sheep to measure the rate of strontium (Sr) absorption from the rumen as an indicator of calcium absorption capacity. Absorption from the rumen after an oral dose of SrCl 2 resulted in a maximum plasma concentration of Sr after 1 h, whereas absorption from the small intestine after injection of SrCl 2 into the abomasum through a cannula occurred more slowly. The second experiment demonstrated that the calcium absorption capacity index of the rumen was significantly greater in 21 lactating Friesian cows (230 ± 66, mean ± SEM) than in 6 mature, nonlactating, nonpregnant heifers (101 ± 21, mean ± SEM). In a third experiment, we compared clinically normal cows at the onset of lactation with those that developed parturient paresis. In cows that developed severe hypocalcemia, plasma concentrations of 1,25(OH) 2 D were significantly elevated (144 ± 60 pg/mL vs. 90 ± 54 pg/mL; means ± SEM) and their rumen calcium absorption index was significantly decreased compared with that of clinically normal cows. Evidence suggested that mobilization of calcium from bone as lactation commenced was significantly depressed in paretic cows compared with those that did not show clinical signs of hypocalcemia. Moreover, ruminal stasis suppressed the absorption of calcium from the rumen. We conclude that measurement of Sr concentration in blood plasma after an oral dose of SrCl 2 into the rumen can be used as an index of rumen calcium absorption capacity under different states of calcium homeostasis.
... The observed increase in calcitriol concentration in multiparous cows is in agreement with results obtained by Horst et al. (1978), who found that cows with parturient paresis had higher concentrations than multiparous cows without that condition. When serum Ca decreases, PTH secretion increases and stimulates the activity of the renal enzyme 1α-hydroxylase, which converts calcidiol into calcitriol. ...
... The primiparous cows had sustained concentration of calcitriol along the study and in the samples taken postpartum concentrations of this hormone were lower than in multiparous cows. Other investigators (Horst et al., 1978;Moore et al., 2000) found similar results but cows were normocalcemic, whereas in our study most cows were hypocalcemic. Data from this study corroborate the findings discussed above but only for multiparous cows. ...
Concentrations of calcidiol, calcitriol, and minerals in blood serum and colostrum of 14 primiparous
and 16 multiparous Holstein dairy cows during short-period prepartum and postpartum were determined
and compared. Blood samples were collected between days 5 and 2 prepartum and 6 h, 12 h, 7 and
21 days postpartum. Nearly 66% of primiparous and 71% of multiparous cows had subclinical postpartum
hypocalcemia. Prepartum serum calcium (Ca) and inorganic phosphorus (P) were higher in primiparous cows;
Ca decreased in both groups at 6 and 12 h and returned to baseline values 7 days postpartum. Calcidiol and
calcitriol concentrations were equal on day 5 prepartum in both groups. In multiparous cows, calcidiol and
calcitriol concentration increased at 6 h postpartum and remained elevated at 12 h postpartum; there were no
changes in primiparous cows for these analytes. The total secretion of Ca in the colostrum from the first milking
was similar in both groups and positively correlated with serum Ca at 6 and 12 h after calving. It is concluded
that postpartum increases in the calcidiol and calcitriol concentration were a normal response to the decrease
of serum calcium concentration only in multiparous cows. The total Ca secretion in the colostrum of the first
milking postpartum does not reflect the grade of hypocalcemia.
... The observed increase in calcitriol concentration in multiparous cows is in agreement with results obtained by Horst et al. (1978), who found that cows with parturient paresis had higher concentrations than multiparous cows without that condition. When serum Ca decreases, PTH secretion increases and stimulates the activity of the renal enzyme 1α-hydroxylase, which converts calcidiol into calcitriol. ...
... The primiparous cows had sustained concentration of calcitriol along the study and in the samples taken postpartum concentrations of this hormone were lower than in multiparous cows. Other investigators (Horst et al., 1978;Moore et al., 2000) found similar results but cows were normocalcemic, whereas in our study most cows were hypocalcemic. Data from this study corroborate the findings discussed above but only for multiparous cows. ...
Parturient paresis and subclinical hypocalcemia are frequent metabolic disorders in dairy cows postpartum. The aim of this study was to determine the effect of postpartum partial milking in the first two milkings on blood serum calcium concentration in dairy cows. Twenty multiparous Holstein dairy cows were randomized into two groups. Cows of group 1 (n = 10) were partially milked at the first and second milking postpartum. Cows of group 2 (n = 10) were completely milked. Blood samples were collected from all animals 5–7 days before calving, within 30 min after calving, and 4, 8, 12, 16, 20, 24, 28, and 32 h after calving for determination of serum calcium (Ca), phosphorus (P), and magnesium (Mg) concentrations. Colostrum production was registered and sampled in the first and second milking. Concentration of Ca in colostrum was determined by atomic absorption spectrophotometry. Serum Ca and P concentrations decreased in both groups after parturition (P < 0.05) and remained low during 32 h postpartum with no difference observed between groups (P > 0.05). Serum concentrations of Mg were stable in all samples and no statistical difference was observed between groups (P > 0.05). Colostrum production was higher in completely milked cows only in the first postpartum milking (P < 0.05), but there was no difference between groups at the second milking. Total Ca secretion in colostrum was higher in the complete milking group at the first and second postpartum milking. Colostrum Ca secretion increased at the second milking with respect to the first one in both groups (P < 0.05). There was no correlation between serum Ca and colostrum Ca (P > 0.05). In this study, the partial milking of colostrum in the first and second milking postpartum did not prevent subclinical hypocalcemia in dairy cows.
... Die Calcium-Mobilisation aus dem Knochen erhöht sich signifikant erst 48 Stunden nach PTH-Stimulation (GOFF et al. 1986). Dieser Adaptationsprozeß kann bei Kühen mit Gebärparese trotz hoher Plasmakonzentrationen von PTH und 1,25-Dihydroxy-Vitamin D 3 (HORST et al. 1978) erheblich verlängert sein, so daß sich klinische Erscheinungen unterschiedlichen Grades bis hin zum Exitus entwickeln (BREVES et al. 1995). Eine verminderte PTH-Sekretion und 1,25-Dihydroxy-Vitamin D 3 -Synthese oder eine erhöhte CT-Sekretion konnten nicht nachgewiesen werden (MAYER 1972, HORST et al. 1978, HORST 1986 (LOTTHAMMER 1980, LITTLEDIKE et al. 1981, OETZEL 1991 • Genetische Disposition. ...
... Dieser Adaptationsprozeß kann bei Kühen mit Gebärparese trotz hoher Plasmakonzentrationen von PTH und 1,25-Dihydroxy-Vitamin D 3 (HORST et al. 1978) erheblich verlängert sein, so daß sich klinische Erscheinungen unterschiedlichen Grades bis hin zum Exitus entwickeln (BREVES et al. 1995). Eine verminderte PTH-Sekretion und 1,25-Dihydroxy-Vitamin D 3 -Synthese oder eine erhöhte CT-Sekretion konnten nicht nachgewiesen werden (MAYER 1972, HORST et al. 1978, HORST 1986 (LOTTHAMMER 1980, LITTLEDIKE et al. 1981, OETZEL 1991 • Genetische Disposition. Die Disposition zur Erkrankung an Gebärparese wird sowohl durch Bullen als auch durch Kühe vererbt und ist mit dem genetischen Milchleistungspotential assoziiert (ROSSOW u. ...
Leipzig, Universiẗat, Diss., 2004. Computerdatei im Fernzugriff.
... For comparison, plasma concentrations of 1,25D are expected to range between~0.04 and 1 nM around calving, with the highest values for paretic cows suffering from severe hypocalcemia [15,16]. The concentrations of Mg 2+ were chosen based on a similar rationale. ...
Efficient coordination between Mg2+ and vitamin D maintains adequate Ca2+ levels during lactation. This study explored the possible interaction between Mg2+ (0.3, 0.8, and 3 mM) and 1,25-dihydroxyvitamin D3 (1,25D; 0.05 and 5 nM) during osteogenesis using bovine mesenchymal stem cells. After 21 days, differentiated osteocytes were subjected to OsteoImage analysis, alkaline phosphatase (ALP) activity measurements, and immunocytochemistry of NT5E, ENG (endoglin), SP7 (osterix), SPP1 (osteopontin), and the BGLAP gene product osteocalcin. The mRNA expression of NT5E, THY1, ENG, SP7, BGLAP, CYP24A1, VDR, SLC41A1, SLC41A2, SLC41A3, TRPM6, TRPM7, and NIPA1 was also assessed. Reducing the Mg2+ concentration in the medium increased the accumulation of mineral hydroxyapatite and ALP activity. There was no change in the immunocytochemical localization of stem cell markers. Expression of CYP24A1 was higher in all groups receiving 5 nM 1,25D. There were tendencies for higher mRNA abundance of THY1, BGLAP, and NIPA1 in cells receiving 0.3 mM Mg2+ and 5 nM 1,25D. In conclusion, low levels of Mg2+ greatly enhanced the deposition of bone hydroxyapatite matrix. The effect of Mg2+ was not modulated by 1,25D, although the expression of certain genes (including BGLAP) tended to be increased by the combination of low Mg2+ and high 1,25D concentrations.
... D3 was once considered as primary cause in cows with milk fever. However these theories have been discarded because both PTH and D3 were normal or even higher in blood of cows with milk fever (Horst et al., 1978). However, a subtype of milk fever occurs in 10% of the cows where production of D3 is insufficient or delayed. ...
... However, cows in which 1,25-(OH) 2 D production is delayed or insufficient account for fewer than 10% of milk fever-affected cows (Goff et al., 1989). Furthermore, many studies have reported that serum 1,25-(OH) 2 D increases to a level equal to or greater than that of normal cows in the early postpartum period, although these cows were fed high-DCAD feed Penner et al., 2008), which affected hypocalcemia (Horst et al., 1978;Goff et al., 2014). Similarly, in the present study, serum 1,25-(OH) 2 D increased in both groups at 0 and 12 h relative to calving. ...
The incidence of hypocalcemia increases in high-parity dairy cows because resorption of bone Ca is delayed in these animals, and they appear to have a reduced ability to absorb Ca from the intestine during the early postpartum period. Difructose anhydride (DFA) III has been shown to promote the absorption of intestinal Ca via a paracellular pathway. However, past studies have not reported this effect in peripartum dairy cows. Therefore, we investigated the effect of DFA III supplementation on Ca metabolism during the peripartum period to determine whether DFA III promotes intestinal Ca absorption via this route. Seventy-four multiparous Holstein cows were separated into DFA and control groups based on their parity and body weight. The feed of the DFA group was supplemented with 40 g/d of DFA III from -14 to 6 d relative to calving. The control group did not receive DFA III. At calving (0 h relative to calving), serum Ca declined below 9 mg/dL in both groups. However, serum Ca concentrations were greater in the DFA group than in the control group at 6, 12, 24, and 48 h relative to calving, and the time required for serum Ca to recover to 9 mg/dL during the postpartum period was shorter in the high-parity cows in the DFA group than in those in the control group. Parathyroid hormone concentrations increased immediately after calving in both groups and were greater in the control group than in the DFA group at 12 and 24 h relative to calving. Serum 1,25-dihydroxyvitamin D concentrations increased at 0 and 12 h relative to calving in both groups and were higher in the control group than in the DFA group at 72 h relative to calving. Serum concentrations of the bone-resorption marker cross-linked N-telopeptide of type I collagen (NTX) were not different between the groups during peripartum period, and serum NTX in all cows was lower at 0, 6, 12, 24, 48, and 72 h relative to calving than at -21, 4, and 5 d relative to calving. Thus, DFA treatment induced faster recovery of serum Ca, although bone resorption was restrained. In conclusion, DFA III promotes intestinal passive Ca absorption via the paracellular pathway during the early postpartum period; this absorption is unaffected by aging.
... Milk fever is usually accompanied by increased concentrations of plasma magnesium (Klimiene et al., 2005;Larsen et al., 2001). Cows suffering from milk fever usually have equal or higher levels of parathyroid hormone than healthy cows (Horst et al., 1978). The reason why some cows develop such severe hypocalcaemia and are affected by milk fever is not entirely understood. ...
... Research considering the effects of l,25(OHlzD, on the bovine immune system are relevant and necessary, since the immunologic consequences of natural elevations of plasma 1,25(OH),D3 concentrations in the dairy cow during the periparturient period (Horst et al., 1978; Reinhardt and Hustmyer, 1987) or artificial increases associated with experimental protocols tor prevention of milk fever (Gaff et al., 1986a; Goff et al., 1986b) are unknown. In the dairy cow, the physiologic transition spanning late pregnancy , parturition and initiation of lactation is associated with dramatic hormonal fluxes and altered immune cell function with increased risk of infection (Newbould, 1976; Lloyd, 1983; Kashiwazaki et al., 1985). ...
... Although circulating concentrations of regulatory hormones yield some information about macromineral homeostasis, these data alone may be insufficient to elucidate the mechanisms of macromineral dysregulation. For example, plasma concentrations of parathyroid hormone (Mayer et al., 1969) and 1,25-dihydroxyvitamin D (Horst et al., 1978) are actually elevated, while plasma calcitonin concentration is decreased (Mayer et al., 1975) immediately preceding, and during, most cases of hypocalcemic parturient paresis in dairy cows. Thus, factors at the tissue level other than hormone concentrations, such as receptor numbers, binding affinity, hormone clearance, and postreceptor signaling, may also be affected during cases of macromineral dysregulation (Horst et al., 1994). ...
Duringthe transitionperiod, dairycows undergolarge metabolic adaptations in glucose, fatty acid, and mineral metabolismtosupportlactationandavoidmetabolicdys- function. The practical goal of nutritional management during this timeframe is to support these metabolic ad- aptations. The National Research Council addressed nu- tritionalmanagementoftransitioncowsforthefirsttime in 2001; however, a substantial amount of research has been reported since this publication was released. Re- sults support 2-group nutritional strategies for dry cows to minimize overfeeding of nutrients during the early dry period but increase nutrient supply to facilitate met- abolic adaptation to lactation during the late dry period. Increasing the amount of energy supplied through di- etary carbohydrate during the prepartum period results in generally positive effects on metabolism and perfor- manceoftransitioncows.Recentresearch,however,sug- gests that the form of that carbohydrate (i.e., starch vs. highlydigestibleneutraldetergentfiber)maybeoflesser importance. Attempts to increase energy supply by feed- ing dietary fat sources or decrease energy expenditure by supplying specific fatty acids such as trans-10, cis- 12 conjugated linoleic acid to decrease milk fat output during early lactation do not decrease the release of nonesterified fatty acids (NEFA) from adipose tissue. Although the view that nutritional means have limited ability to enhance hepatic export of NEFA as triglycer- ides in lipoproteins in ruminants has become dogma, recent evidence suggests that nutrients such as choline or specific fatty acids may enhance this process in transi-
... Sinkt der Blut-Ca-Spiegel dabei drastisch, kann dies zu einer Beeinträchtigung der Nerven-und Muskelfunktionen führen, was die typischen klinischen Anzeichen des Milchfiebers hervorruft (Allen und Sansom, 1985). In den meisten Fällen wird die Hypokalzämie von einer Hypophosphatämie, in manchen Fällen auch von einer mehr oder weniger ausgeprägten Hypermagnesiämie begleitet (Ender et al., 1971;Horst et al., 1978;Allen und Sansom, 1985). Die hypokalzämische Gebärparese besitzt eine Inzidenz von ca. 5 -10 % (Lesch et al., 2006;Oetzel, 2002a;Philippo et al., 1994). ...
Das Ziel der Arbeit war es, einen Zusammenhang zwischen dem nativen Kalium(K)gehalt im Dürrfutter, welches in den letzten Wochen der Trockenstehphase verabreicht wurde, und dem peripartalen Kalzium-Stoffwechsel der Kühe nachzuweisen. Für den Versuch wurden 12 Milchkühe, die sich zu Versuchsbeginn 5 Wochen vor dem errechneten Abkalbungstermin befanden, auf 2 Gruppen (K35 und K15) aufgeteilt. Während der präpartalen Versuchsphase erhielt Gruppe K35 eine Ration mit K-reichem Heu (35 g/kg TS), Gruppe K15 erhielt eine Ration mit K-armem Heu (15 g/kg TS). Während der Bilanzperiode, die nach der Abkalbung begann und sich über einen Zeitraum von 7x24 h erstreckte, erhielten die Kühe eine in der Startphase übliche Ration. Zu den Versuchszeitpunkten Versuchsbeginn, 3, 2 und 1 Woche a.p., 3 Tage a.p., Abkalbung, 24 h p.p. und Bilanztag 1-7 wurden Blut- und Harnproben entnommen. Während der Bilanzperiode wurden zudem täglich über 24 h die Kot- und Harnausscheidung sowie die Milchleistung gemessen und Kot-, Milch- sowie Futterproben analysiert. Im Blut wurden Mineralstoffe, pH-Wert, 1,25(OH)2VitD sowie die Knochenmarker carboxyterminales Telopeptid des Typ I Kollagens, Crosslaps, knochenspezifische alkalische Phosphatase und Osteocalcin bestimmt. Im Harn wurden Mineralstoffe, pH-Wert, Netto-Säure-Basen-Ausscheidung (NSBA), BSQ (Basen-Säure-Quotient) und Hydroxyprolin bestimmt. Die Knochenmarker im Serum zeigten nach der Abkalbung in beiden Gruppen einen ähnlichen Verlauf. Die Ergebnisse lassen darauf schliessen, dass Knochenmarker geeignete Parameter zur Beurteilung des Knochenstoffwechsels sind. Der tiefere Harn-pH-Wert und die geringere NSBA der Gruppe K15 ante partum sprechen für azidotische Veränderungen im Säure-Basen-Haushalt, welche vermutlich durch die präpartale Fütterung der K-armen Ration ausgelöst wurde. Es konnte nicht gezeigt werden, ob der K-Gehalt des Futters einen Einfluss auf die Ca-Absorption im Magen-Darm-Trakt ausübt. Der optimalere Verlauf der 1,25(OH)2VitD-Konzentrationen im Serum der Kühe der Gruppe K15 scheint hier jedoch Zusammenhänge erkennen zu lassen.
... Popoff (1982) and Matsui et al (1983) found a relationship between hyperparathyroidism and HCE in sheep. Similarly during parturient paresis (milk fever) in the cow, parathyroid hormone (PTH) concentration is higher (Horst et al, 1978;Allen and Sansom, 1986;Bar et al, 1988) and calcitonin (CT) concentration is lower (Mayer et al, 1975;Allen and Sansom, 1986) than normal values. ...
Serum levels of calcium (Ca), inorganic phosphorus (P), magnesium (Mg), parathyroid (PTH) and calcitonin (CT) hormones of fat-tail Awassi ewes were determined during the last month of pregnancy. The incidence of hypocalcaemia (HCE) was 13.4% of the obstetrical cases examined. Twenty-six (81.3%) of 32 ewes with HCE were 4 yr of age or older. Significant decreases (p less than 0.01) in serum Ca levels from normal values or controls (n = 6; 10.04 +/- 0.22% (w/w)) to pathological values (4.30 +/- 0.35% (w/w)) caused severe clinical manifestations in 75% of affected ewes. This HCE was accompanied by a significant increase in the PTH level (142.6 +/- 9.1 pmol/l in comparison to 99.7 +/- 9.3 pmol/l in controls, p less than 0.05) and significant decrease in serum CT level (98.2 +/- 7.6 pg/ml in comparison to 144.6 +/- 25.7 pg/ml in controls; p less than 0.05). Intravenous administration of Ca borogluconate yielded normal Ca levels which were accompanied by a decrease in serum PTH levels and an increase in CT levels to normal values.
... This is about two or three times as much Ca as is present in the extracellular fluid. Almost all cows will experience some degree of hypocalcemia at this time, and plasma concentrations of PTH (Mayer et al., 1979) and 1,25-(OH)2D (Horst, 1978b) responds within minutes to reduce loss of Ca into the urine. However, renal reabsorption of Ca is of limited capacity, adding less than 1 g Ca to the extracellular pool (Ramberg et al., 1984). ...
Known and possible interactions between Ca, P, Mg, parathyroid hormone (PTH), calcitonin (CT), vitamin D and its metabolites, and interactions of each of these with other factors plus complexities and possible variations between and within domestic animal species, such as age, sex, physiologic state (i.e., pregnancy, lactation and growth) and diet, make Ca, P and Mg metabolism extremely dynamic and complex. Many advances have been made in understanding these interactions and how each of these factors is controlled, secreted or metabolized within the body. Some interactions among these factors are discussed in detail, mostly with a view to understanding mechanisms by which homeostasis of Ca, P and Mg is maintained. Also, three of the major diseases of mineral metabolism of cattle (milk fever, grass tetany and wheat pasture poisoning) provide excellent models to study the complex soil, plant and animal interrelationships among Ca, P, Mg and the factors that influence and control the ultimate utilization of these minerals in animals. These diseases are used to illustrate some of the interactions among many of the factors that influence Ca, Mg and P metabolism in domestic animals.
... Research considering the effects of l,25(OHlzD, on the bovine immune system are relevant and necessary, since the immunologic consequences of natural elevations of plasma 1,25(OH),D3 concentrations in the dairy cow during the periparturient period (Horst et al., 1978;Reinhardt and Hustmyer, 1987) or artificial increases associated with experimental protocols tor prevention of milk fever (Gaff et al., 1986a;Goff et al., 1986b) are unknown. In the dairy cow, the physiologic transition spanning late pregnancy, parturition and initiation of lactation is associated with dramatic hormonal fluxes and altered immune cell function with increased risk of infection (Newbould, 1976;Lloyd, 1983;Kashiwazaki et al., 1985). ...
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active metabolite of vitamin D, and delta 22-26-F3-1,25-dihydroxyvitamin D3 (delta 22-26-F3-1,25(OH)2D3), a synthetic analog with a high affinity for the vitamin D receptor, significantly inhibited interferon-gamma (IFN-gamma) secretion in 24- and 48-h cultures of pokeweed mitogen (PWM) and ovalbumin (OVA) stimulated peripheral blood mononuclear leukocyte (MNL) from adult, OVA-sensitized dairy cattle. Vitamin D-induced inhibition of IFN-gamma production was most pronounced in MNL cultures supplemented with 1,25(OH)2D3 at 1.0 nM or more, a concentration equal to or exceeding that in plasma of cows with clinical hypocalcemia. Secreted IFN-gamma was undetectable in all resting MNL cultures. Ultra-low concentrations (0.0001, 0.001, and 0.01 nM) of 1,25(OH)2D3 had no effect on IFN-gamma secretion by PWM-stimulated bovine MNL, unlike a previous study in other species demonstrating enhancement of IFN-gamma secretion at these concentrations. Preincubation of MNL with.
... Furthermore, although circulating concentrations of regulatory hormones yield some information about macromineral homeostasis, these data alone may be insufficient to elucidate the mechanisms of macromineral dysregulation. For example, plasma concentrations of PTH (Mayer et al., 1969) and 1,25-OHD (Horst et al., 1978 ) are actually elevated, whereas plasma calcitonin concentration is decreased (Mayer et al., 1975) immediately preceding and during most cases of hypocalcemic parturient paresis in dairy cows. Thus, factors (other than hormone concentrations) at the tissue level, such as receptor numbers, binding affinity, hormone clearance, and postreceptor signaling may also be affected during cases of macromineral dysregulation (Horst et al., 1994). ...
Four multiparous lactating cows (175 to 220 d in milk) were used in a 4 x 4 Latin square design to assess the effects of four doses (0.0, 0.5, 1.0, 1.5 microg/kg of body weight) of lipopolysaccharide (LPS; Escherichia coli 0111:B4) on circulating concentrations of macrominerals and vitamin D metabolites. Treatments were dissolved in 100 ml of sterile saline and infused intravenously over a period of 100 min. Blood was sampled immediately before infusion (0 h), at 60-min intervals for 8 h, and at 24 and 48 h postinfusion. Vitamin D metabolites were analyzed in samples collected at 0, 2, 6, 24, and 48 h only. Serum Ca and P concentrations decreased after LPS infusion, but there was no effect on serum magnesium concentration. Plasma 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 were not affected by LPS infusion; however, when analyzed as 0 vs. all other doses of LPS combined, there was a tendency for plasma 1,25-(OH)2 vitamin D3 concentration to decrease when cows were infused with LPS. The inflammatory response elicited by LPS altered plasma macromineral concentrations, a result that may have important implications for calcium homeostasis and metabolic health of lactating dairy cows.
This paper describes the mechanism of calcium and phosphorus homoeostasis in ruminants in order to provide a clearer understanding of the aetiology of bovine and ovine parturient paresis, in which this homoeostatic mechanism breaks down, and of the prophylactic measures by which the incidence of the disease may be reduced.
The objective of the studies was to determine the efficiency of parenchymatous organs and energetic metabolism in the course of clinical hypocalcaemia in dairy cows during the perinatal period. The studies were carried out in 1999-2002 on farms raising from a few head of cattle to several dozen dairy cows of black and white (BW) and Holstein-Friesian (HF) race and the crossbreeds of these races in the Lublin region. Clinical symptoms of hypocalcaemia in 47 cows appeared from some hours after parturition to about a week later. The control group consisted of 12 clinically healthy cows. The levels of total Ca, WKT, total bilirubin, urea as well as AST, ALT, AP in blood were determined. At the initial time of the studies significantly higher levels of WKT were registered in all diseased groups; they differed statistically compared with the cows of the control group. The cows with clinical symptoms demonstrated increased ALT and AST activity, yet this was greatly differentiated for individual specimens. The activity of AST exceeded top levels in the group of cows with symptoms of coma and lying cows (gr. II and IIIb). The ALT activity showed great differentiation and high values, often over the standards, especially in the IIIrd group of cows. The disorders of ASP and ALT levels were also accompanied by high mean values of bilirubin, which was especially seen in the group of cows with symptoms of acute hypocalcaemia. Both in this group and in some of the cows with hypocalcaemia yet without reduced consciousness, high values of urea were observable. The activity of AP did not change in the studied groups of cows.
Hypocalcemia (milk fever) continues to be a common clinical entity in dairy cattle. Approximately 5% to 10% of adult dairy cattle are affected by the condition. Cows that are affected with milk fever are at a greater risk of developing hypocalcemia at subsequent lactations than are nonaffected cows. This article discusses the mechanisms that cause hypocalcemia as well as the three stages of clinical signs of the condition. The clinical pathologic findings and commonly used treatments are considered. The major predisposing factor that leads to hypocalcemia is the sudden increase in the demand for calcium that results from the production of colostrum and milk in periparturlent and postparturlent cows. Orally administered calcium products that are now on the market can decrease the incidence of clinical milk fever relapse if they are used as an adjunct to traditional intravenous calcium therapy. These oral products have also been demonstrated to be effective as (1) a prophylactic treatment to prevent clinical hypocalcemia in some situations and (2) a treatment for mildly affected hypocalcemic cows.
In milk fever (parturient paresis), calcium homeostatic mechanisms, regulated by parathyroid hormone and 1,25-dihydroxyvitamin D, fail to maintain normal blood calcium concentrations, resulting in severe hypocalcemia. The precise nature of the endocrine defect is unknown. Secretion of parathyroid hormone and production of 1,25-dihydroxyvitamin D is similar in most cows with milk fever or without. However, there are some cows that fail to produce adequate 1,25-dihydroxyvitamin D at the onset of lactation. These tend to be cows that will suffer prolonged hypocalcemia and relapse after treatment. Assuming that most cows produce adequate amounts of both hormones, the next logical cause of milk fever might be a failure of tissues to respond to calcium-regulating hormones. Older cows are more likely to develop milk fever than younger ones. We have found that tissue 1,25-dihydroxyvitamin D receptor concentrations decline with age, leaving the tissues less able to respond to 1,25-dihydroxyvitamin D. We also have found that tissue 1,25-dihydroxyvitamin D receptor concentrations increase during pregnancy and lactation in the cow. Intestinal 1,25-dihydroxyvitamin D receptor concentration does not appear to be different in cows with or without milk fever in cows of similar ages. However, intestinal 1,25-dihydroxyvitamin D receptor numbers decrease precipitously at parturition, which may in part be responsible for the development of hypocalcemia in dairy cattle.
The effects of stage of lactation and breed on total and ionized calcium in blood plasma were determined for eight Holstein and eight Jersey cows fed a diet containing .25% Ca during the dry period and fed a diet with .50% Ca after calving. Blood samples were obtained by jugular venipuncture at 2-wk intervals from 4 wk before calving through wk 10 of lactation. Total and ionized Ca contents of fresh plasma were determined potentiometrically with an ion-specific electrode. Total Ca in plasma also was determined by atomic absorption spectrophotometry. Average concentrations determined by atomic absorption were approximately .7 mg/dl higher than those for the ion-specific electrode. Plasma total and ionized Ca were lower in both breeds at calving than any other time during the sampling period. Jersey cows had lower total Ca (7.47 mg/dl) and ionized Ca (4.25 mg/dl) than Holsteins (8.10 and 4.66 mg/dl) on day of calving. Ionized Ca as a percentage of total calcium increased from 55 to 57% at parturition and then decreased slowly to 53% at peak lactation. Changes in percentage of ionized Ca may indicate the contribution of bone resorption relative to dietary Ca in meeting the Ca requirement for lactation.
Plasma osteocalcin, or plasma bone GLA protein (BGP), total plasma alkaline phosphatase activity and urinary hydroxyproline excretion of twenty-four pregnant dairy cows (thirteen in their first or second pregnancy, i.e. low parity, and eleven in their third or more pregnancies, i.e. high parity) were measured from 7 weeks before parturition until 1 week after parturition. Seven weeks before parturition the cows' ration was changed to one containing either 0.22% magnesium (low magnesium, LMg) or 0.82% magnesium (high magnesium, HMg) in the dry matter, and the potassium content of both rations was increased to approximately 4.1% in the dry matter to reduce the absorption of magnesium. Plasma BGP levels decreased significantly (P less than 0.01) as parturition approached while total plasma alkaline phosphatase activity and urinary hydroxyproline excretion did not. Magnesium supply and parity had no significant effect on this decrease. The overall plasma concentration of BGP, total plasma alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio in the prepartum period were affected by parity (P less than 0.05) with higher values in the lower parity cows. A significant positive correlation (r = 0.58, P less than 0.01) was found in all cows between plasma BGP level at parturition and the percentage of the bone surface covered with osteoblasts; however, plasma BGP was not correlated either with other histomorphometric variables or with total alkaline phosphatase activity during this time.
Parturient paresis (milk fever) is a hypocalcemic disorder caused by the onset of lactation in the dairy cow. In most cows a complete recovery follows a single iv calcium treatment to correct the acute hypocalcemia. However, about 20% of cows treated for parturient paresis experience recurring episodes of hypocalcemia (relapses) requiring further treatment. Analysis of plasma from 8 nonrelapsing parturient paretic and 11 relapsing parturient paretic cows revealed differences in plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations before and during the development of hypocalcemia. In nonrelapsing cows, plasma 1,25-(OH)2D increased to 4- to 5-fold as plasma calcium concentrations declined during the first stage of parturient paresis. In relapsing cows, decreases in plasma calcium concentrations during the first stage of parturient paresis were accompanied by just a 2- to 2.5-fold increase in plasma 1,25-(OH)2D. Plasma 1,25-(OH)2D eventually increased 4- to 5-fold in the relapsing cows, but this response was delayed 24-48 h compared with the response in the nonrelapsing cows. Plasma PTH concentration profiles were similar in relapsing and nonrelapsing cows, suggesting that renal 25-hydroxyvitamin D 1 alpha-hydroxylase was temporarily refractory to stimulation by PTH in the relapsing cows. In both groups of cows recovery from parturient paresis began about 12-24 h after plasma 1,25-(OH)2D concentrations had increased 4- to 5-fold. These data imply that lack of production of 1,25-(OH)2D is an important factor in predisposing the cow to relapses of parturient paresis and is critical for recovery from the hypocalcemia associated with the onset of lactation.
Significant advances have been made in the last 30 years in the understanding of Ca, PO4, and Mg homeostasis in ruminants. Despite these advances, the primary cellular or molecular lesions responsible for failure of homeostasis have yet to be identified. Suggested causes, such as primary hormone deficiencies, have been eliminated, and we now believe that aging and nutrition can reduce the ability of intestine, bone, and kidney to respond rapidly to the hormone signals responsible for homeostasis during rapid increases in demand for these minerals. Further research is required before these lesions can be identified and new knowledge applied to the development of economical, effective programs that prevent milk fever and hypomagnesemic tetany. Until then, diseases such as milk fever will continue to affect 8 to 9 per cent of our dairy cows, and dairy farmers will continue to spend millions of dollars a year for treatment of the primary disease and the many secondary problems that result from these diseases.
Thirteen Israeli Friesian cows (3.71 average calvings) in the second or later lactation, fed a daily diet containing 90 g of Ca and 50 g of P, were injected once intramuscularly with 700 micrograms 1 alpha-hydroxy-vitamin D3 in order to investigate its placental transfer and its subsequent metabolism in the neonate. The injection of the vitamin 96 to 24 h before calving slightly increased plasma Ca at parturition, whereas uninjected controls displayed a prominent hypo-calcemia. On the 10th and 20th d after calving, difference in the plasma Ca concentration of the two groups was not significant. At parturition, plasma parathyroid hormone concentration was significantly higher and plasma 1,25-dihydroxyvitamin D lower in the control than in the treated cows. At parturition the plasma concentrations of Ca, parathyroid hormone, hydroxyproline, and 24,25-hydroxyvitamin D were higher in the calves than in their dams. Plasma concentrations of 25-hydroxyvitamin D were markedly higher and 1,25-hydroxyvitamin D was slightly higher in cows than in their offsprings.
This paper describes the mechanism of calcium and phosphorus homeostasis in dairy cows in an effort to provide a clearer understanding of the rationale behind current management and supplementation practices. Specifically addressed is the need to keep prepartum dietary calcium intake at less than or equal to 50 g/d to minimize the incidence of milk fever. Also discussed is the need to increase National Research Council recommendations for postpartum dietary calcium from 2.7 to 3.4 g/kg milk. This is particularly important during the first 1 to 2 mo of lactation to maintain calcium balance.
The relative potencies of 1,25-dihydroxycholecalciferol, 24-F-1,25-dihydroxycholecalciferol, and 24,24-F2-1,25-dihydroxycholecalciferol at three doses (25, 100 or 400 micrograms) were assessed in nonlactating Jersey cows. The 24,24-F2-1,25-dihydroxycholecalciferol induced a significantly greater hypercalcemia and hyperphosphatemia than did 1,25-dihydroxycholecalciferol. The 24-F-1,25-dihydroxycholecalciferol was intermediate in its hypercalcemic and hyperphosphatemic potency. Urinary hydroxyproline excretion rate and plasma hydroxyproline concentration were not significantly increased by treatment with any of the compounds. This indicates that these compounds did not stimulate bone resorption in nonlactating, nongravid cows. Renal function was significantly impaired in cows that received a 400-micrograms dose of any compound. There was a severe reduction in glomerular filtration rate (up to 42%) and urine specific gravity. Renal function was most severely affected in cows treated with 24,24-F2-dihydroxycholecalciferol and was evident even at the 100-micrograms dosage level.
Intravenous infusion of synthetic bovine parathyroid hormone for 96 h increased 1,25-dihydroxyvitamin D, Mg, Ca, and hydroxyproline in plasma of pregnant cows within 16, 24, 48, and 72 h, respectively. Plasma Ca concentration was maximal at the end of the 96-h infusion (15.1 mg/100 ml). Plasma concentration of 1,25-dihydroxyvitamin D at 96 h was twice that before parathyroid hormone infusion, indicating that parathyroid hormone stimulated 1,25-dihydroxyvitamin D production in the presence of hypercalcemia. The urinary excretion of hydroxyproline indicated that at least 48 h of parathyroid hormone stimulation was required to stimulate bone resorption in the pregnant cow. Eight periparturient cows were on a high Ca diet prepartum. Four cows were treated with intravenous parathyroid hormone prior to parturition. Four cows were untreated. All four untreated cows developed parturient paresis. None of the cows treated with parathyroid hormone developed parturient paresis. However, two cows that received parathyroid hormone for less than 24 h prior to parturition became hypocalcemic, but not recumbent. Plasma Ca concentrations remained within normal limits in the two other cows that received greater than 60 h parathyroid hormone infusion prior to parturition. We conclude that exogenous parathyroid hormone (1-34) can prevent parturient paresis if administered at least 60 h prior to parturition.
Ten pregnant heifers and 10 pregnant cows (three or more pregnancies) were assigned to groups of five and fed either the recommended (low) amount of calcium or excess (high) calcium in their diet for 4 wk before parturition to determine the influence of prepartum calcium intake and age on hormonal control of peripartum calcium homeostasis. After parturition all groups received a diet with calcium adequate for lactation. Jugular blood samples from 21, 14, 7, 6, 5, 4, 3, 2, and 1 d prepartum through 0, 1, 2, 3, 5, 7, 14 and 21 d postpartum were assayed for concentration of parathyroid hormone, calcitonin, calcium, magnesium and phosphorus. Heifers and cows receiving high calcium diets had higher calcium and lower parathyroid hormone in blood serum before parturition than animals receiving the low calcium diets. Cows, but not heifers, fed high calcium diets exhibited severe hypocalcemia at parturition, remained hypocalcemic for 3 d and had low serum calcitonin. Regardless of dietary group, concentrations of parathyroid hormone and magnesium in serum increased after the first week of lactation. Feed intake during lactation, corrected for metabolic body weight, was similar for both dietary treatments and ages. Milk production per kilogram metabolic body weight was highest during the first week of lactation for cows fed low calcium diets before parturition. There was no correlation between hypocalcemia and loss of calcium in colostrum or milk. Feeding low dietary calcium to cows in the prepartum period was effective in the prevention of severe hypocalcemia at parturition. In contrast, dietary treatment of heifers had no effect on serum calcium concentration at parturition.(ABSTRACT TRUNCATED AT 250 WORDS)
Allen, W.M. & Sansoni, B.F. Milk lever and calcium metabolism. J. vet. Pharmacol. Therap. 8, 19–29.
W.M. Allen, Department of Functional Pathology, AFRC Institute for Research on Animal Diseases, Campion, Newbury, Berkshire RC16 ONN, England.
Complexity of vitamin D metabolism and its interaction with calcium-regulating hormones in ruminants have received little attention. Data of this report focus on the uniqueness of the bovine in its metabolism of vitamin D. Also, control of vitamin D metabolism in the periparturient cow and the ultimate mode of action of the steroid hormone 1,25-dihydroxyvitamin D at its target tissues relative to the onset of parturient paresis are reviewed.
Twenty Jersey cows were fed one of four prepartal diets: a)low calcium, low phosphorus (LCLP); b) low calcium, high phosphorus (LCLP); c) high calcium, low phosphorus (HCLP); or d)high calcium, high phosphorus (HCHP). Diets were fed for about 4 weeks prepartum. Blood samples were taken periodically, and the collected plasma analyzed for concentrations of calcium, phosphorus, hydroxyproline and 1,25 dihydroxyergocalciferol plus 1,25-dihydroxycholecalciferol (1,25-(OH)2D). Cows fed the LCLP and LCHP diets, when compared to cows fed the HCLP diet, had: a) greater concentrations of plasma 1,25-(OH)2D and hydroxyproline prepartum; b) greater plasma calcium concentrations at parturition; and c) less incidence (0 versus 4 cases) of parturient paresis. Thus, low calcium diets, regardless of dietary phosphorus intake, seemed to activate calcium homeostatic mechanisms before parturition by stimulating both bone and gut. Cows fed the HCLP diet had greater plasma calcium concentrations at parturition than did cows fed the HCHP, even though there was no measurable effect on plasma 1,25-(OH)2D and hydroxyproline concentrations during the prepartal period. It seems possible that the beneficial effect of low dietary phosphorus, when dietary calcium is high, may be a result of a prepartal increase in efficiency of absorption of calcium and phosphorus from the gut caused by increased binding of 1,25-(OH)2D to intestinal receptors.
Our objective was to characterize changes in vitamin D metabolites of plasma in Jersey cows fed a prepartum low-calcium diet. Eight cows were fed a high-calcium diet (80 g/day) and eight were fed a low-calcium diet (8 g/day) at least 14 days before parturition. Calcium concentrations in plasma decreased after initiation of feeding either diet, but cows fed low-calcium diet tended to have lower prepartum calcium and phosphorus and greater peripartal calcium in plasma. Hydroxyproline in plasma was greater during peripartal period in cows fed low-calcium diet. Prepartum 1,25-dihydroxyvitamin D in plasma tended to be greater in cows fed low calcium. Increases in 1,25-dihydroxyvitamin D were only 2 and 3 days after initiation of the low-calcium diet; during the first 2 days after parturition, however, 1,25-dihydroxyvitamin D tended to be lower in those cows fed low calcium. As parturition neared, 24,25-dihydroxyvitamin D tended to be lower in cows fed the low calcium-diet. Usual early postpartum changes in calcium phosphorus, magnesium, 1,25-dihydroxyvitamin D, and hydroxyproline were seen during first few days after initiation of feeding low calcium. Thus, we propose that the preventative action of the low-calcium diet is associated with preparation of the calcium homeostatic mechanism several days before the calcium demand of initiation of lactation.
Continuous infusion of 1,25-dihydroxyvitamin D3 in the bovine elevated 1,25-dihydroxyvitamin D3 in plasma. Plasma 1,25-dihydroxyvitamin D3 remained elevated until infusions were discontinued. Increased 1,25-dihydroxyvitamin D3 was associated with hypercalcemia (11 to 12 mg/dl) that continued for several days postinfusion. Elevated 1,25-dihydroxyvitamin D3 also was associated with a significant 70% enhancement of lymphocyte proliferation in cells treated with concanavalin A. Cessation of infusion of 1,25-dihydroxyvitamin D3 resulted in the return of 1,25-dihydroxyvitamin D3 in plasma and lymphocyte proliferative response to preinfusion amounts. Proliferation in response to pokeweed mitogen was significantly inhibited on d 3 of infusions of 1,25-dihydroxyvitamin D3. Administration of parathyroid hormone for 4 d resulted in a sustained hypercalcemia (approximately 13 mg/dl) and a transient 1-d increase in 1,25-dihydroxyvitamin D3 in plasma. Parathyroid hormone treatment generally did not affect the response of bovine lymphocytes to mitogen. In vivo elevation of 1,25-dihydroxyvitamin D3 is either moderately immunostimulating or exerts no effect on mitogen-stimulated proliferation of lymphocytes. These results contrast with the in vitro results suggesting that 1,25-dihydroxyvitamin D3 is only immunosuppressive.
Most dairy cows experience some degree of hypocalcemia during the periparturient period. There is, however, a sub-group of dairy cows that experience a breakdown in their ability to maintain plasma calcium and, consequently, suffer from severe hypocalcemia. This condition is also known as milk fever and usually occurs in cows in their third or greater lactation. The precise metabolic lesions responsible for the onset of milk fever have not yet been defined. Research has shown that milk fever is not the result of inadequate production of calcitropic hormones (parathyroid hormone and 1,25-dihydroxyvitamin D), but rather is more likely a result of inadequate receptor numbers or receptor dysfunction in the target cell of these hormones. This report reviews vitamin D and calcium metabolism, giving emphasis to 1,25-dihydroxyvitamin D receptor regulation and function as related to the periparturient dairy cow. The report also focuses on providing insights into nutritional (anionic diets) and endocrine strategies that have proved useful in milk fever management.
Dietary cation-anion difference has been defined as milliequivalents of (Na+K)-(Cl+S) per kilogram of DM and has a direct impact on blood acid-base metabolism. As this difference decreases, one or more of the following blood parameters change: increased H+, decreased HCO3-, and decreased pH. These changes are accompanied by reduced urinary HCO3- excretion and pH as compensatory mechanisms. Although other minerals have an impact on acid-base metabolism, the four minerals used in dietary cation-anion difference have the greatest effect. Manipulation of acid-base balance can be used to manipulate other biological functions to benefit health and productivity of cows. Low cation-anion difference prepartum can mitigate hypocalcemia peripartum via increased urinary Ca, blood-ionized Ca, and responsiveness to Ca homeostatic hormones. These changes reduced the incidence of paresis and increased productivity by reducing the severity and length of hypocalcemia in all cows (periparturient), regardless of the occurrence of paresis. Reduced cation-anion differences prepartum have been related to a reduced severity of udder edema, likely related to increased renal loss of water and unchanged water intake. However, the effects on acid-base balance cannot be ruled out because of effects on biochemical and transport processes. Elevated cation-anion difference in lactation has been shown to increase DMI and production and to mitigate the effects of heat stress. Because production and heat stress are acidogenic, elevated cation-anion difference improves blood-buffering capacity to cope with H+. In heat stress, elevated water intake with elevated cation-anion difference cannot be ignored. Other diseases related to metabolic acid, such as laminitis and ketoacidosis, may be influenced by elevated cation-anion difference in lactation; however, research in these areas has not been forthcoming.
Mature Friesian cows were given silage plus either an alkaline or an acidic concentrate mix during the last 28 days of pregnancy in two experiments. There were no significant differences in plasma calcium, phosphorus or magnesium concentrations before parturition but the blood ionised calcium and plasma chloride concentrations were significantly increased, together with a lower blood pH and acid-base excess in the cows on the acid diet. The mean 1,25-dihydroxyvitamin D concentrations tended to increase before parturition in the cows on the acid diet compared with the alkali diet in experiment 1 and were significantly higher in experiment 2. At parturition, the acid-fed cows had higher mean plasma calcium concentrations and significantly more of them had values > 2.0 mmol litre-1 than the alkali-fed groups, and the plasma 1,25-dihydroxyvitamin D and parathyroid hormone concentrations were related to these different plasma calcium concentrations. The acidic diets therefore appeared to prevent the onset of hypocalcaemia at parturition by increasing the plasma 1,25-dihydroxyvitamin D concentration before parturition.
The effects of feeding diets with different milliequivalents (meq) of dietary [(Na+ + K+) - (Cl- + SO4=)] to dairy cows during the last seven weeks of pregnancy on their acid-base status and calcium mobilisation rate around parturition were studied. Ten monozygotic twin pairs of pregnant cows (five pairs of parity 1 or 2, and five pairs of parity 3 or more) were allocated to two diets which were formulated to provide either -4 meq (anion diet) or +572.5 meq (cation diet) of [(Na+ + K+) - (Cl- + SO4=)] kg-1 dietary dry matter (DM). The daily rations consisted of 4 kg grass hay and 7 kg concentrates. Changes in meq of dietary [(Na+ + K+) - (Cl- + SO4=)] were achieved by adding KCl, K2SO4 and (NH4)2SO4 (anion diet) or K2CO3 (cation diet) to basal concentrates. Plasma calcium concentration and blood acid-base parameters were not affected by dietary treatment. However, urinary calcium excretion was markedly higher and urinary pH and bicarbonate excretion significantly lower in cows fed the anion diet than in cows fed the cation diet. The responses to hypocalcaemia induced by an intravenous infusion of EDTA solution were similar in the cows fed either diet.
Twenty-one paretic and 30 nonparetic periparturient ambulatory cows were studied together with 13 non-pregnant control cows. Blood samples were collected during a time period of 6 hours before or after parturition and from nonpregnant cows. A severe hypocalcemia (-44%) and hypophosphatemia (-69%) were found in the paretic vs. nonparetic periparturient animals, whereas serum magnesium concentrations were not altered. Serum alkaline phosphatase activity was modestly (-12%) but not significantly decreased in the paretic vs. nonparetic periparturient cows. Serum osteocalcin concentrations, which reflect osteoblast activity, were strikingly low during the periparturient period and more in the paretic cows but the difference between the paretic (-36%) and nonparetic animals was not statistically significant. In the paretic cows, serum 1,25-dihydroxyvitamin D concentrations were significantly increased (+53%) and those of hydroxyproline decreased (-18%) compared with the nonparetic animals. Serum estradiol levels were markedly increased in the periparturient vs. nonpregnant cows and more in the paretic animals, but, again, the difference between the paretic (+47%) and nonparetic animals was not statistically significant. Serum retinol concentrations were significantly lower (-18%) in the paretic vs. nonparetic periparturient cows probably reflecting increased lactation in the paretic animals. Collectively, the results indicate very low bone metabolic activity in the periparturient vs. nonpregnant cows and support the hypothesis of both osteoblast and osteoclast functions being impaired in the paretic animals.
Milk fever is the clinical disease associated with severe hypocalcemia in dairy cows. In this experiment, we tested the hypothesis that calcium homeostasis is a result of a decreased concentration of receptors for 1,25-dihydroxyvitamin D in the tissues of cows that develop milk fever. Samples of colon mucosa were obtained for analysis of vitamin D receptor concentration in a longitudinal study of Jersey cows during the 2 wk before and after parturition. In the first study, 21 cows fed an alfalfa hay diet were biopsied every 3rd d from 2 wk before to 2 wk after calving. The concentration of vitamin D receptor in the colon during late gestation was three- to fourfold higher than the concentration of vitamin D receptor in the colon mucosa in nonpregnant cows (90 +/- 8 vs. 26 +/- 5 fmol/mg of protein). At parturition, colon concentration of vitamin D receptor decreased to 66 +/- 7.5 fmol/mg of protein. During early lactation, concentrations of vitamin D receptor in the colon were similar to precalving concentrations. There was no significant difference of concentrations of vitamin D receptor in the colon prior to calving, at calving, or in early lactation between cows that did develop milk fever and those that did not. Results were similar in a second study, in which 7 cows were fed a high cation alfalfa diet, and 6 cows were fed the same diet with anionic salts added. Those data do not support the hypothesis that decreased concentrations of vitamin D receptor prior to calving is a causative factor of milk fever within the Jersey breed. However, a decline of concentrations of vitamin D receptor in tissue at calving may reduce the ability of all cows to respond to the calcium demands of lactation.
Milk fever is a complex metabolic disorder that occurs at the onset of lactation. Clinical symptoms of this disease include inappetence, tetany, inhibition of urination and defecation, lateral recumbency, and eventual coma and death if left untreated. The hallmark of this disease is severe hypocalcemia, which probably accounts for most of the clinical signs associated with a milk fever episode. Several factors have been consistently associated with increased incidence of milk fever, including parturition and initiation of lactation, advancing age, breed, and diet. Of the various methods used in attempts to control the disease, the most progress has been made in dietary management. Until recently, most attention has focused on manipulating the levels of dietary calcium to control milk fever incidence; results, however, have been inconsistent, except for those diets containing very low (8 to 10 g/d) concentrations of Ca. During the past decade, there has been renewed interest and research in the use of dietary anions (Cl- and SO4(2-) in controlling milk fever. An outgrowth of this research has been the surprising realization that dietary K is significant (perhaps more significant than Ca) in determining the susceptibility of dairy cows to milk fever. This knowledge has expanded the understanding of the pathogenesis of milk fever and has focused attention on research designed to study methods for neutralizing the detrimental effects of dietary K excess on periparturient animal health. This report discusses various practical strategies and potential research areas for managing the dietary forage components to minimize the effects of K on milk fever incidence.
Eight periparturient Holstein Friesian cows were examined for plasma tartrate-resistant acid phosphatase (TRAP) activity to assess the degree of bone metabolic activity and to evaluate the association between the change in calcium (Ca) concentration and bone metabolism during the periparturient period. Milk fever occurred in 1 of 8 cows just after parturition. Plasma TRAP activities did not markedly change in 5 of 8 cows during the experimental period. The changing rate of Ca between preparturition and just after parturition was under -20% in 3 of 8 cows, and low TRAP activities were observed in 2 of these 3 cows. This study suggests that cows with a low TRAP activity are at risk of developing milk fever in comparison to cows with high TRAP activity. Temporary increases of parathyroid hormone were observed in 7 cows, but not in the cow with milk fever.
Adequate blood calcium concentrations are vital for the normal function of mammals. Mechanisms for maintaining normal blood calcium function adequately most of the time; however, occasionally they fail and calcium homeostasis is compromised. Milk fever or periparturient hypocalcemia in dairy cattle is a well-documented example of a breakdown in the mechanisms of calcium homeostasis. This disease occurs at the time of parturition and is unique to adult dairy animals. The disease results from the inability of animals to cope with the sudden demand for calcium in support of colostrum formation. Animals developing the disease become hypocalcemic and require intravenous calcium to survive. The precise metabolic disorder(s) responsible for the onset of milk fever is still being debated. This report will highlight some of the current concepts related to the causes and prevention of milk fever in dairy cattle, as well as contrasting differences in calcium demands that exist between dairy cattle, humans and rats at the onset of lactation.
Previous studies have proved the possibility of preventing parturient hypocalcaemia by zeolite A supplementation during the dry period, and a recent in vitro study has indicated a marked calcium (Ca) as well as phosphorus (P) binding effect of zeolite A in rumen fluid solutions. Because of the connection between the Ca and P homeostatic systems, the preventive effect against parturient hypocalcaemia may arise from zeolite induced decreased availability of dietary Ca as well as P. In the present study, the expected Ca and P binding capacity was challenged by feeding high and low levels of dietary Ca and/or P to zeolite A treated dry cows. Twenty-one pregnant dry cows were assigned to four experimental groups receiving a dry cow ration unsupplemented or supplemented with extra Ca and/or P. During the last 2 weeks of the dry period all cows additionally received 600 g of zeolite A per day. A high level of dietary P prepartum significantly decreased the plasma Ca concentration before as well as immediately after calving (day 0-3). Conversely, the plasma inorganic phosphate concentration was higher among these cows than among cows receiving no supplemental P. The prepartum dietary Ca level significantly affected the serum 1,25-dihydroxyvitamin D concentration during zeolite supplementation, whereas the periparturient plasma Ca concentration was apparently not affected by the dietary Ca level. During zeolite A supplementation plasma parathyroid hormone was significantly higher among cows receiving additional P. The urinary deoxypyridinoline/creatinine ratio was not affected by the prepartal dietary Ca or P level. Serum aluminium (Al) was significantly higher during zeolite A supplementation than during the preceding period, indicating partial destruction of the zeolite in the intestinal tract with subsequent release and absorption of Al. It is suggested that the effect of prepartum zeolite supplementation on the periparturient Ca homeostasis depends on the level of Ca as well as P in the dry cow ration.
The administration of parathyroid extract within 2 hr postpartum to first calf heifers, normal mature cows, and mature cows with a past history of milk fever did not appreciably alter the plasma levels of calcium, magnesium, or alkaline phosphatase. Plasma inorganic phosphorus was increased moderately in most of the animals by the action of parathyroid extract. At the time of parturition mature animals showed a greater decrease in calcium and inorganic phosphorus and a greater increase in magnesium than did the younger animals. Alkaline phosphatase remained relatively constant in all animals. Thirty-one parturitions were studied and six cases of milk fever observed. Data suggest that milk fever can result from either a low level of calcium or a low level of both phosphorus and calcium. Cases of milk fever which relapsed were of the latter type. Parturient cows were not responsive to parathyroid extract and its administration just after calving had no apparent effect on the occurrence or severity of milk fever.
A new, highly sensitive and relatively convenient method has been developed for the determination of 1,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D2 in blood plasma. The method involves a simplified and more specific extraction procedure, new rapid and effective methods of purification, and a competitive binding assay using intestinal cytosol from rachitic chicks. The method also includes a procedure for stabilizing the cytosol binding protein and a convenient procedure for the separation of bound from free 1,25-dihydroxyvitamin D3 with the use of polyethylene glycol. The recovery of 1,25-dihydroxyvitamin D3 during extraction and purification is 68% and triplicate determinations can be made on a 5-ml plasma sample. With this method, rachitic chick plasma, plasma from anephric patients, and plasma from patients suffering severe endstage renal failure show no detectable 1,25-dihydroxyvitamin D, while normal human values have been found to be 29 ± 2 pg/ml.
Twenty of 60 control cows fed a "normal" diet prepartum developed parturient paresis whereas none of 37 fed a low-calcium (13 to 18 g/cow per day) diet prepartum developed the disease.
Immunoreactive calcitonin and calcium concentrations were determined on 581 plasma samples collected during 23 studies on 20 cows. Sample collection in each study was begun approximately 1 mth prior to parturition and continued for about 1 mth after parturition. The cows were grouped according to the degree of hypocalcemia encountered at parturition. The parturient paresis group consisted of 10 cows which developed severe hypocalcemia (3.91 ± 0.22 mg/100 ml, mean ± SE) accompanied by paresis; the nonparetic hypocalcemic group consisted of 5 cows which developed severe hypocalcemia (5.70 ± 0.30 mg/100 ml) but not paresis; and the control group consisted of 8 cows which experienced only a mild hypocalcemia (8.50 ± 0.27 mg/100 ml) at parturition. In the prepartal period prior to the onset of hypocalcemia, the respective mean plasma calcium concentrations (± SE) of the 3 groups were 10.1 ± 0.11, 9.95 ± 0.20, and 10.2 ± 0.17 mg/100 ml. The development of severe hypocalcemia in the parturient paresis and nonparetic hypocalcemic groups was not accompanied by an increase in plasma calcitonin concentration. Furthermore, plasma calcitonin concentration of these 2 groups was less than that of control cows during the parturient period as well as during the mth before and the mth after parturition. The plasma calcium nadir at parturition was positively related to the mean prepartal (encompassing the period from 30 days until 60 hr before parturition) plasma calcitonin concentration (r = 0.57, t = 3.14, P<0.005); i.e., the lower the prepartal plasma calcitonin concentration the more severe the hypocalcemia at parturition. These observations suggest that the development of hypocalcemia at parturition is not due to an increased secretion of calcitonin, but instead they suggest that parturient hypocalcemia may be associated with a diminished prepartal secretion of calcitonin.
Thyroparathyroidectomy of rats on a diet low in calcium reduces production of 1,25-dihydroxycholecalciferol from 25-hydroxycholecalciferol to negligible levels within 40 hr, and increases production of another metabolite, called Va. Parathyroid extract, at a dose of 20 units per day, prevents these changes. When 40 units per day of parathyroid extract is given 48 hr after thyroparathyroidectomy, 1,25-dihydroxycholecalciferol production is restored almost to control levels within 36 hr. The change brought about by parathyroid extract cannot be attributed to resulting changes in serum calcium or phosphorus concentration. It appears that the parathyroid hormone serves as a tropin for production of 1,25-dihydroxycholecalciferol, the hormonal form of vitamin D responsible for calcium mobilization from intestinal contents and bone.
Parturient paresis is a metabolic disease which is associated with parturition and initiation of lactation. It is characterized by low total serum calcium and inorganic phosphorus. Failure of the calcium homeostatic mechanism at parturition is associated with: (1) advanced age of cattle—older cattle absorb less dietary calcium and may have less exchangeable bone calcium; (2) too great an intake of calcium, over 100 to 125 g/ day; (3) reduced intake at parturition, greater in older cattle; (4) overconditioned cows which appear to go off-feed easily; and (5) increased hormones, estrogen, and glucocorticoids at parturition which may reduce serum calcium.Attempts to prevent failure of this mechanism include: (1) feeding prepartal diets low in calcium; (2) adjustment of the dietary calcium-to-phosphorus ratio; (3) feeding acidic diets, mineral acids, or ammonium chloride prepartum; (4) short-term administration of 90 to 100 g of calcium chloride daily; (5) feeding massive doses of vitamin D prepartum; (6) prepartum administration of 25-hydroxycholecaIciferol, a metabolite of vitamin D3.While much is known, the real cause of failure in the calcium homeostatic mechanism remains unanswered.
Jejunal calcium absorption was measured from test solutions containing 1.0, 2.5, 5, and 10 mM calcium (as calcium gluconate). Absorption rates increased progressively as luminal calcium concentration was increased, although there was a tendency toward saturation of the absorptive process at the higher concentrations. Calcium absorption was higher in normal young adults than in normal subjects over age 60. In both groups a 300 mg calcium diet for 4-8 wk enhanced calcium absorption relative to absorption rates after 4-8 wk on a 2,000 mg calcium diet. This adaptation was more definite and dramatic in the young than in the old subjects. Indirect estimates suggest that adaptation to a low calcium diet and the higher absorption in young than old normal subjects are mediated by an increased V(max) rather than a decreased K(m).
An organ culture system was used to examine the effects of oestrogens on the response of 5-day-old mouse calvaria to parathyroid hormone (PTH). Parathyroid hormone released calcium and phosphate from the bone and this was associated with an increase in glucose consumption, an accumulation of citric acid and an inhibition of citrate oxidation. Oestradiol, oestriol, oestrone and ethinyl oestradiol all inhibited the PTH-induced release of calcium. The accumulation of citrate was prevented without the PTH-induced block on citrate oxidation being removed, and this was explained in terms of a reduction in glycolysis. Oestradiol, oestriol and oestrone appeared to be of equal potency. However, ethinyl oestradiol was active at much lower doses but appeared to be toxic at higher levels.
Charcoal premixed with dextran of average molecular weight 80,000 almost instantly adsorbs free insulin but rejects antibody-bound insulin. The use of such dextran-coated charcoal makes simpler and more rapid the immunoassay of insulin in biologic fluids, using radioisotope dilution with 131I-insulin and “biopsy” of the insulin pool by antibody to insulin. The procedure here described yields a straight line graph when insulin added is plotted against insulin recovered.
1. A combination of balance and isotope techniques has been used to study the effects of age and dietary calcium content on Ca metabolism in forty-two wether sheep.
2. The amount of Ca absorbed by young growing animals varied significantly with intake. The percentage of the dietary Ca absorbed, however, remained unchanged. In older animals the amount of Ca absorbed was not altered by changes in intake, but decreased slightly with age.
3. Retention of Ca was directly related to the amount of Ca absorbed and was independent of age or breed. Furthermore, nearly all the Ca absorbed above the minimum mean amount required for maintenance was retained.
4. Faecal endogenous loss of Ca also was related to the amount of Ca absorbed. Values for faecal endogenous Ca were much lower than those used in the calculation of dietary require-ments by the Agricultural Research Council (1965).
5. Urinary Ca excretion was variable, and was not related to age or changes in dietary Ca intake.
6. Increased absorption of Ca in young growing animals was accompanied by a decreased rate of bone resorption, but the rate of bone accretion remained unchanged. Changes in dietary Ca in older animals had no effect on either of these two processes. Results indicate that bone resorption is the main pathway governing Ca homoeostasis. Both the rates of Ca accretion into bone and resorption from bone decreased with age.
7. Neither the rapidly exchangeable Ca pool (P) nor the slowly exchangeable bone pool (E) was altered by changes in dietary intake in young or mature animals. Both, however, decreased in size with age.
8. The size of the slowly exchangeable pool (E) was directly related to the rate of Ca accretion into bone. 9. The results were used to calculate dietary Ca requirements of sheep gaining weight at different rates, and these values have been compared with values recommended by the Agricultural Research Council (1965).
RECENT procedures for the immunological assay of protein hormones in human plasma1-3 require the routine preparation of hormones labelled with iodine-131 of high specific activity.
(1) The fecal excretion of orally administered Ca45 is a sensitive indication of the calcium status of the rat; (2) placing normal rats on a low calcium diet for as little as 2 days greatly increased their ability to absorb Ca45 from the tract; (3) the specific activity of labeled calcium at the site of absorption had little effect upon its absorption; (4) in general, younger rats absorbed more Ca45 than did older ones although there was no significant difference between 6 1/2 and 16-month-old animals; (5) for meaningful studies of this type, interpretations must include consideration of exchange reactions, and care must be given to initial selection of diets and animals, preparation of animals for the experiment, and dietary management during the experimental period.
Thyrocalcitonin content of thyroid gland extracts from normal postparturient cows was 3.9 times greater than in cows with
postparturient paresis. The parafollicular cells in diseased cows were less numerous and appeared to have discharged their
secretory products. An abrupt release of thyrocalcitonin near parturition may be related to the development of the hypocalcemia
and hypophosphatemia in this disorder.