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Biomedical subjects

R L Horst

Publications and source records attributed to R L Horst.

At least 73 records · Page 4Linked to original sources

Field trials of an oral calcium propionate paste as an aid to prevent milk fever in periparturient dairy cows.

Trials were conducted to test the efficacy of a calcium propionate paste as an aid to prevent milk fever and to improve the health of dairy cows. Each calcium propionate treatment tube supplied 37 g of calcium. In trials involving Holstein herds and a Jersey herd, two (trials 1 and 2) or three (trial 3) calcium propionate tubes were given at calving and again at 12 h after calving. For the Jersey herd, calcium propionate treatment (two tubes) reduced the incidence of milk fever from 50% in control cows to 29% in treated cows. Plasma obtained 24 h after calving from treated cows had higher calcium, lower NEFA, and lower beta-hydroxybutyrate concentrations than did plasma from control cows. No other benefits of calcium propionate treatment were significant for health or for productivity of the cows. Calcium propionate treatment had no significant effects on blood calcium, NEFA, or beta-hydroxybutyrate in the Holstein herds studied. However, calcium propionate did reduce the number of cows with subclinical hypocalcemia (< or = 7.5 mg/dl of plasma calcium) at 24 h after calving in both trials involving Holstein cows. Calcium propionate treatment was beneficial in reducing subclinical hypocalcemia in all trials and reduced the incidence of milk fever in a herd having a problem with milk fever.

3-Hydroxybutyric Acid↗

Effect of bovine somatotropin administered to periparturient dairy cows on the incidence of metabolic disease.

Thirty-eight dry, pregnant Jersey cows were assigned to diet and bST treatment in a 2 x 2 factorial design. During the dry period, half of the cows were fed a normal TMR (0.4% Ca; 0.3 to 0.4% P), and half of the cows were fed a high Ca TMR (1.5 to 1.6% Ca; 0.4 to 0.7% P). The high Ca diets were designed to induce milk fever and were relatively cationic (194 to 293 meq/kg) compared with the normal diets (-131 to 30 meq/kg). A standard dairy diet was fed to all cows postcalving. Cows received subcutaneous injections of either an oil-based excipient or 500 mg of bST in an oil-based excipient every 14 d from 28 d before expected calving until approximately 14 d postcalving. Peripartal bST treatment decreased the incidence of clinical mastitis, did not affect incidence of milk fever, and increased the duration, but not the incidence, of ketosis in mature Jersey cows. Blood data confirmed the clinical responses and indicated that treated cows mobilized more bone Ca than did controls, as was evidenced by increased hydroxyproline concentrations. Treatment with bST did not affect blood concentrations of 1,25-dihydroxyvitamin D, Ca, or Mg. High Ca diets increased the incidence of milk fever and downer cow syndrome compared with normal diets. The effect of bST on mastitis and milk production must be considered as preliminary given the small size of the study. Although bST treatment increased Ca mobilization, the effect was insufficient to prevent milk fever in this model.

Animals↗

Acidosis effects on insulin response during glucose tolerance tests in Jersey cows.

The effect of metabolic alkalosis and acidosis on insulin response to glucose tolerance tests was determined for cows fed a high cation diet to induce a state of metabolic acidosis. The anion diet to induce a state of metabolic acidosis. The glucose tolerance test (500 mg of glucose/kg of BW infused i.v. over 10 min) caused a rapid increase in plasma glucose and insulin concentrations. Plasma glucose concentrations were highest, and plasma insulin concentrations were lowest, during metabolic acidosis. These results suggest that insulin secretion is impaired during metabolic acidosis, which may reduce tissue uptake of glucose. Correction of metabolic acidosis by oral administration of sodium bicarbonate prior to glucose tolerance testing increased blood pH and bicarbonate concentrations and partially restored insulin response to the glucose tolerance test. Interestingly, sodium bicarbonate also caused an elevation in plasma cortisol concentrations. We concluded that glucose utilization is altered in cows with metabolic acidosis. The correction of acidosis associated with diseases such as diarrhea and ketosis may improve the therapeutic benefit of glucose infusions used to treat these diseases.

Acidosis↗

Effects of dietary calcium and phosphorus on vitamin D metabolism and calcium absorption in hamster.

We studied the following responses to restriction of dietary calcium and phosphorus in the growing hamster: (i) serum concentrations of calcium, inorganic phosphorus, magnesium, and vitamin D metabolites; and (ii) calcium transport by ileum. Diets fed were normal calcium with normal or low phosphorus or low calcium with normal or low phosphorus. We found serum 1 alpha,25-dihydroxycalciferol (1,25-[OH]2D) concentration did not differ significantly among the diet groups. Calcium absorption, measured as serosal/mucosal calcium concentration ratio produced by everted ileal sac, was greater in the low calcium, normal phosphorous group than in all other groups. The other groups did not differ from one another in calcium absorption. Feeding the low calcium, normal phosphorus diet increased inorganic phosphorus and magnesium but decreased calcium concentration in serum in comparison with the three other diets. Both low phosphorus diets were without effect on serum calcium, but the low calcium, low phosphorus diet increased serum inorganic phosphorus and magnesium above that of the normal calcium, low phosphorus diet. Ileal calcium absorption in hamster (i) was independent of serum 1,25-(OH)2D concentration; (ii) increased in response to low dietary calcium if dietary phosphorus was normal; and (iii) was independent of dietary calcium, if dietary phosphorus was low. Despite increased calcium absorption, serum calcium was decreased in the low calcium-normal phosphorus group as compared with all other groups. Feeding low calcium diets increased serum inorganic phosphorus and magnesium as compared with feeding the corresponding normal calcium diets (i.e., independently of whether dietary phosphorus content was normal or low). These studies demonstrate that the interrelationships between calcium absorption and vitamin D and mineral metabolism in hamster differ from other mammals.

Absorption↗

9,13-Di-cis-retinoic acid is the major circulating geometric isomer of retinoic acid in the periparturient period.

This study examines changes in the geometric isomers of retinoic acid (RA) during late gestation and early lactation. Blood samples were collected from dairy cows at 14 days prepartum and continuing until 14 days postpartum. Assays were done using solid-phase extraction followed by quantitation of RA isomers by reverse-phase HPLC. The major RA in plasma of periparturient cows was 9,13-di-cis-RA. 9,13-Di-cis-RA was present at < or = 1 ng/ml 10 days prior to parturition and was elevated to approximately 2 ng/ml by 1 day prepartum, then increased to > 4 ng/ml by 1 day postpartum. 9,13-Di-cis-RA remained at approximately 4 ng/ml for at least 14 days postpartum. Plasma all-trans-RA, 13-cis-RA, and 9-cis-RA were also elevated during the periparturient period with the most pronounced changes (approximately 25-30% increase) occurring between the day of parturition and 4 days postpartum. 9,13-Di-cis-RA was 116- and 30-fold less competitive than 9-cis-RA for binding to human retinoid X receptors (hRXR)alpha and hRXR beta, respectively. Because of this relatively low affinity for the RXR, it seems that 9,13-di-cis-RA per se would contribute marginally, if at all, to the pleiotropic effects attributed to 9-cis-RA. This study establishes that profound changes in vitamin A metabolism occur in late gestation and early lactation. Because 9,13-di-cis-RA is a metabolite of 9-cis-RA, these data imply that there are dramatic fluctuations in 9-cis-RA which are more profound than other physiologically occurring RAs, particularly all-trans-RA.

Animals↗

The role of dietary calcium in the physiology of vitamin D toxicity: excess dietary vitamin D3 blunts parathyroid hormone induction of kidney 1-hydroxylase.

We studied the effects of dietary calcium (Ca) restriction and excess vitamin D3 on tissue 25-hydroxyvitamin D-1-hydroxylase (1-OHase) and 1,25(OH)2D/25-OH-D-24-hydroxylase (24-OHase) activities in rats. Effects were studied in four groups of rats, with each group receiving one of the following diets: a control diet consisting of normal Ca and normal vitamin D3 (NC), NC plus excess (75,000 IU/week) vitamin D3 (NCT), low Ca and normal vitamin D3 (LC), or LC diet with excess vitamin D3 (LCT). Rats fed the low-Ca diets (LC and LCT) had elevated plasma parathyroid hormone (PTH) concentrations, increasing > 3-fold relative to rats fed the normal Ca diets. The elevated concentrations of PTH in LCT rats did not result in increased plasma 1,25-dihydroxycholecalciferol [1,25(OH)2D3] (NC = 115 +/- 7 pg/ml; LCT = 99 +/- 11 pg/ml). Plasma 1,25(OH)2D in LC rats, however, was increased significantly (615 +/- 110, P = < 0.001). There were no differences in either plasma Ca or phosphorus between the LC and LCT groups. Dietary Ca restriction led to an 18-fold stimulation in renal 1-OHase activity in LC rats (P = < 0.01), while 1-OHase in the LCT rats was marginally but significantly elevated 2.3-fold (P = < 0.05). The ability of PTH to downregulate renal 24-OHase and the 1,25-dihydroxyvitamin D receptor (VDR) during prolonged Ca restriction remained intact, irrespective of vitamin D status. Also, the metabolic clearance rate for 1,25(OH)2D3 was enhanced by feeding excess vitamin D3, which was likely a result of the substantial elevations in intestinal (25-fold) and renal (46-fold) 24-OHase activities in the LCT and NCT groups, respectively. These data indicate that calcium restriction accompanied by excess vitamin D3 is attended by impaired responsiveness of renal 1-OHase to PTH and enhanced metabolic clearance of 1,25(OH)2D.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Identification of 9-cis,13-cis-retinoic acid as a major circulating retinoid in plasma.

In the course of measuring the concentrations of retinoic acids (RA) in bovine plasma, a major peak was observed which comigrated with 9-cis-RA on normal-phase high-performance liquid chromatography. Rechromatography of this retinoic on reverse-phase high-performance liquid chromatography showed that it was distinct from 9-cis-,13-cis-, and all-trans-RA, but comigrated with 9-cis,13-cis-retinoic acid (9,13-di-cis-RA). This retinoid was identified as 9,13-di-cis-RA based on its chemical, spectral, and chromatographic properties. Plasma concentrations of 9,13-di-cis-RA increased from < or = 0.5 ng/mL at birth to 5-6 ng/mL by 48 h of age in the calf. The 9,13-di-cis-RA was also a major circulating product of 9-cis-RA dosed intramuscularly to rats; conversely, intravenous administration of 9,13-di-cis-RA produced circulating 9-cis-RA in the rat. 9,13-Di-cis-RA had little or no affinity for cellular retinoic acid binding protein types I and II. This study establishes 9,13-di-cis-RA as a naturally-occurring retinoid under physiological conditions, shows that it undergoes interconversion with 9-cis-RA, and emphasizes a need for careful chromatography to resolve 9-cis-RA and 9,13-di-cis-RA. This is consistent with in vivo 13-cis isomerization operating to modify the concentration and perhaps the activity of 9-cis-RA in vivo.

Animals↗

Regulation of L-selectin and CD18 on bovine neutrophils by glucocorticoids: effects of cortisol and dexamethasone.

The responsiveness of bovine neutrophil L-selectin and CD18 to in vivo glucocorticoid administration was characterized by flow cytometric analysis. Blood was sampled intensively from dairy cows treated for 3 days with placebo, cortisol, or dexamethasone. Immunostaining was performed on whole blood (100 microliters) that was left unstimulated or was stimulated with platelet-activating factor (PAF; 1 microgram/ml blood) prior to incubation with fluorescein isothiocyanate-conjugated monoclonal antibodies against L-selectin and CD18. Results were expressed as the percentage of positive-staining cells and as mean fluorescence intensity (MFI) of those cells. Total leukocyte count and leukocyte differentials were also performed on all blood samples. Dexamethasone caused nearly complete down-regulation of L-selectin (P < .01) on the surface of gated cells and reduced to half the MFI of CD18 (P < .01). Compared with values for the placebo group, dexamethasone began to cause L-selectin down-regulation within 8 h after the first injection and these effects persisted until 48 h after the third injection. This was correlated in time with an acute reduction in the proportion of cells that stained positive for L-selectin (from 98% before dexamethasone injections to a low of 17% by 40 h after the first injection). Dexamethasone also caused leukocytosis and neutrophilia during this time interval. In contrast, CD18 down-regulation was delayed until 16 h after the second dexamethasone injection and persisted for roughly 8 days. However, at no time during the experiment did dexamethasone influence the proportion of gated cells staining positive for CD18 (always 100%). Effects of cortisol were generally similar in pattern to those of dexamethasone but were more subtle and more readily detected when PAF was added to blood prior to immunostaining. These results strongly suggest that one mechanism of the anti-inflammatory action of glucocorticoids is to induce dramatic down-regulation of L-selectin and CD18 adhesion molecules on blood neutrophils.

Animals↗

An audio-video system for automated data acquisition in the clinical environment. LOTAS Group.

OBJECTIVE: Our objective was to develop an audiovideo data acquisition system that facilitates studying the activities of anesthesia care providers in the clinical environment. METHOD: Ceiling-mounted miniature video cameras, vital sign monitors, and videocassette recorders (VCRs) were interfaced to digital computers in two patient admitting areas and two operating rooms of a trauma center. This video data acquisition system network (VASNET) is simple to operate. Insertion of a videotape activates the system and begins video overlay of updated vital signs onto the video image every 5 sec. Recorded data is passed via a local area network, allowing remote monitoring of the data acquisition process. To facilitate analysis of the video at a later time, the image, soundtrack, and vital signs data are stamped with the same time code. Each tape is initialized by recording the data file name and wall clock time for 30 sec at the start of taping. This initialization enables comparison of the video recordings with anesthesia, surgical, and nursing records. RESULTS: During 2 years of operation, VASNET was used to record over 100 cases of acute trauma management. Vital signs overlaid onto the video image identified when patient monitors were in use and providing data. Participants found videotape review useful in assessing their own performance. VASNET was nonintrusive and acquired data with minimum user interaction. In one operating room, separate from the trauma center, VASNET was installed to function as a remote monitor, with the option of videotaping. Although users were aware of when videotaping occurred, once patient management was underway, the activities of the anesthesia care providers did not appear to be influenced by the videocassette recording. Equipment maintenance was not excessive. The most frequent problems were changes to the VCR control settings and disconnection of the power supply or interface connections. CONCLUSIONS: Videotapes of the process of anesthetizing and resuscitating trauma patients provided a record of the activities of anesthesia care providers. Video vignettes may be useful training tools. Excerpts from real scenarios can be incorporated into anesthesia stimulators. The soundtrack and timing of real events from such video acquisition may be useful in the development of multimedia simulations of trauma patient resuscitation. The data collection may be useful for research into human performance, ergonomics, training techniques, quality assurance, and certification of anesthesia care providers in trauma patient management. Potential additional applications of VASNET include remote monitoring of patients in the operating room, in the intensive care unit, during transportation, in hazardous environments, and in the field. Such VASNET telemetry may facilitate the availability of expert opinions during medical and other consultations.

Anesthesia↗

Assessing adequacy of cholecalciferol supplementation in chicks using plasma cholecalciferol metabolite concentrations as an indicator.

Cholecalciferol (vitamin D) deficiency rickets remains an occasional problem in poultry. Diagnosis currently relies on analysis of feed and histopathological examination of bone. These experiments were designed to provide data that might allow diagnosis of cholecalciferol deficiency on the basis of plasma concentrations of 25-hydroxycholecalciferol, a circulating metabolite of cholecalciferol. Day-old broiler chicks were fed corn-soybean meal or purified ingredient cholecalciferol-deficient diets supplemented with 0, 5, 10, 15, 20, 25, 37.5 or 75 micrograms cholecalciferol/kg diet. Plasma and bone samples were collected 21 d later. Chicks fed the unsupplemented purified ingredient diet became truly deficient, having no detectable plasma concentrations of the cholecalciferol metabolites 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol, or 24,25-dihydroxycholecalciferol. Chicks fed the corn-soybean meal diet without supplementation had low but detectable concentrations of both 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol in plasma. Body weight, bone calcium and bone phosphorus concentrations of chicks fed the corn-soybean meal diet suggest that the cholecalciferol requirement of broiler chicks is at least 10 micrograms/kg diet. At this dietary level of cholecalciferol, plasma 25-dihydroxycholecalciferol concentration was 12.5 nmol/L. One hundred percent of the theoretical maximal response in body weight and bone calcium content was seen at 20 micrograms cholecalciferol/kg diet, which increased plasma 25-hydroxycholecalciferol concentration to 25 nmol/L in the chicks fed the corn-soybean meal diet. These data provide a nomogram of plasma 25-dihydroxycholecalciferol concentration that can be expected from including different concentrations of cholecalciferol in the diet, and also offer a means of diagnosing cholecalciferol deficiency in field cases of tickets.

24,25-Dihydroxyvitamin D 3↗

Administration of 13-cis-retinoic acid to dairy cattle. 1. Plasma retinoid concentrations and lymphocyte blastogenesis.

Effects of administration of 13-cis-retinoic acid on concentrations in plasma of retinoic acid isomers, retinol, and beta-carotene and on in vitro mitogen-stimulated lymphocyte blastogenesis of peripheral blood mononuclear leukocytes were evaluated in Holstein cattle. Treatments consisted of i.m. injections of 0 (vehicle only), 100, 200, or 400 mg of 13-cis-retinoic acid in dimethylsulfoxide for 7 d. Concentrations of 13-cis- and all-trans-retinoic acids in plasma and in mononuclear leukocytes were elevated in a dose-dependent manner by administration of 13-cis-retinoic acid. Treatment with 13-cis-retinoic acid, however, had no effect on concentrations of retinol and beta-carotene in plasma. In vitro DNA synthesis in unstimulated and mitogen-stimulated mononuclear leukocyte cultures was unaffected by in vivo administration of 13-cis-retinoic acid. In contrast, in vitro supplementation of unstimulated and mitogen-stimulated mononuclear leukocyte cultures with 13-cis-retinoic acid inhibited DNA synthesis relative to unsupplemented cultures. In conclusion, elevated plasma and intracellular concentrations of 13-cis- and all-trans-retinoic acids produced by repeated i.m. administrations of 13-cis-retinoic acid did not affect peripheral blood mononuclear leukocyte function, as measured by the in vitro blastogenic response of peripheral blood lymphocytes.

Animals↗

Administration of 13-cis-retinoic acid to dairy cattle. 2. Phenotype of blood leukocytes and production of immunoglobulin.

Eight Holstein dairy cattle were assigned randomly to treatments in three replicate experiments evaluating the effects of 13-cis-retinoic acid on mononuclear leukocyte function. Treatments were i.m. injections of 0 (vehicle only), 100, 200, or 400 mg/d of 13-cis-retinoic acid in dimethylsulfoxide for 7 consecutive d. Peripheral blood was collected before treatment and periodically for 18 d after initiation of treatments. Parameters measured were IgM production in vitro by blood lymphocytes, serum Ig concentrations, and the phenotype of peripheral blood mononuclear leukocytes. Administration of 13-cis-retinoic acid had no effect on in vitro Ig production induced by pokeweed mitogen; however, supplementation of the same cultures with 13-cis-retinoic acid enhanced production of polyclonal IgM. Serum Ig concentrations and total numbers of peripheral blood leukocytes and numbers within mononuclear leukocyte subsets were unaffected by treatment with 13-cis-retinoic acid. Experimentally induced elevations in the concentrations of serum and intracellular retinoic acids did not affect mononuclear leukocyte function in vivo.

Animals↗

Milk fever and dietary cation-anion balance effects on concentration of vitamin D receptor in tissue of periparturient dairy cows.

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.

Animals↗

In vivo parathyroid hormone stimulates in vitro bone resorption by bovine monocytes.

Cells of the monocyte-macrophage lineage have been thought to play a role in bone resorption. We examined the effects of in vivo administration of parathyroid hormone and 1,25-dihydroxyvitamin D3 on the ability of monocytes to degrade bone in vitro. Administration of parathyroid hormone for 4 d resulted in sustained hypercalcemia and a transient 1-d increase in plasma 1,25-dihydroxyvitamin D3. Parathyroid hormone significantly stimulated bone degradation by monocytes 2.6 times more than that of pretreatment controls. Parathyroid hormone treatment significantly enhanced (threefold) release of superoxide anion by monocytes stimulated with phorbol 12-myristate 13-acetate and increased migration of monocytes to bone particles in vitro. Continuous 7-d infusion of 1,25-dihydroxyvitamin D3 (50 micrograms/d) elevated plasma 1,25-dihydroxyvitamin D3 until infusions were discontinued. Increased 1,25-dihydroxyvitamin D3 was associated with hypercalcemia, which continued for several days postinfusion. In vivo administration of 1,25-dihydroxyvitamin D3 did not affect in vitro ability of monocytes to degrade bone. We concluded that in vivo administration of parathyroid hormone enhanced in vitro responsiveness of isolated monocytes in a manner consistent with a role for monocytes in bone remodeling. Furthermore, these data suggested that circulating monocytes could be a useful experimental model for further studies on parathyroid hormone responsiveness and bone resorption for the cow with milk fever.

Animals↗

Phorbol 12-myristate 13-acetate and 1,25-dihydroxyvitamin D3 regulate 1,25-dihydroxyvitamin D3 receptors synergistically in rat osteosarcoma cells.

In this study, we examined the effect of activation of protein kinase C (PKC) pathways on the regulation of 1,25-dihydroxyvitamin D receptors (VDR) in rat osteosarcoma (ROS) 17/2.8 cells. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) resulted in a time- and dose-dependent increase in VDR expression in ROS cells. Treatment of ROS cells with 4alpha-phorbol 12,13-dedeconate, a PKC-inactive phorbol ester, had no effect on VDR expression. Oleoyl acetyl glycerol (OAG), a synthetic diacylglycerol, stimulated VDR up-regulation in ROS cells. The PKC inhibitors (H-7, staurosporin, and sphingosine) all blocked PMA-mediated up-regulation of VDR in a dose-dependent manner. We next examined the interaction of 1,25(OH)2D3 and PKC activation by PMA on the regulation of VDR in ROS cells. We found that PMA or 1,25(OH)2D3 treatment alone resulted in a 50 and 200% increase in VDR, respectively. PMA treatment alone resulted in a 50% increase in VDR protein and a marginal 20% increase in VDR mRNA. 1,25(OH)2D3 up-regulation of VDR was associated with a 2-fold increase in VDR mRNA. In contrast, co-treatment of ROS cells with PMA and 1,25(OH)2D3 resulted in a synergistic 10-fold induction of VDR mRNA and the appearance of a 7.2 kb VDR transcript. VDR protein was also synergistically up-regulated by combined PMA and 1,25(OH)2D3 treatment of ROS cells. Scatchard analysis demonstrated that the synergistic effect of PMA and 1,25(OH)2D3 on VDR protein expression was not associated with any change in the affinity of VDR for 1,25(OH)2D3. The synergistic effect of 1,25(OH)2D3 and PMA on VDR expression supports a link between PKC signal pathways and the function of VDR.

Animals↗

In vivo regulation of rat intestinal 24-hydroxylase: potential new role of calcitonin.

24-Hydroxylase is found in many mammalian tissues and is required as an initial step in the deactivation of vitamin D3 metabolites and most of its active analogs. We studied the regulation of intestinal 24-hydroxylase (I-24-OHase) activity and messenger RNA (mRNA) expression in rats as influenced by calcium and vitamin D status. Rats were fed vitamin D-replete diets containing either normal calcium (1.0-1.2%, designated NC) or low calcium (0.02%; designated LC). Half of the NC and LC rats received 25,000 IU vitamin D3 three times weekly, orally, and were designated NCT and LCT, respectively. We found that I-24-OHase mRNA expression was up-regulated in rats receiving excess vitamin D3 (NCT and LCT). We observed, however, that the up-regulation was much more dramatic in the LCT group and exceeded by 4.5-fold that observed in the NCT group. Plasma calcium was also elevated in the NCT group (12.6 +/- 0.2 mg/dl), but not the LCT group (10.5 +/- 0.15 mg/dl). We, therefore, examined the possibility that calcitonin released in response to hypercalcemia may have suppressed the induced expression of I-24-OHase mRNA in the NCT group. The plasma calcitonin level was higher in the NCT group (36.14 +/- 2.46 pg/ml) relative to that in the LCT group (19.38 +/- 2.28 pg/ml). Thyroparathyroidectomy also resulted in a 2-fold (P < 0.001) increase in I-24-OHase activity in the NCT group, a response that was reversed (within 4 h) with a single dose of calcitonin (100 IU/rat). Calcitonin administration to LCT rats also resulted in a significant (P < 0.001) 5-fold reduction in I-24-OHase mRNA expression. These data suggest that calcitonin is a potent negative regulator of I-24-OHase mRNA expression and I-24-OHase activity and that the release of calcitonin may block an important pathway for the inactivation of vitamin D3 metabolites in intestine and, thereby, potentiate the toxicity of vitamin D3 during periods of its excess consumption.

Animals↗

Calcium salts for treating hypocalcemia: carrier effects, acid-base balance, and oral versus rectal administration.

Oral Ca salt supplements are being used to combat hypocalcemia in dairy cows. The absorption of these Ca supplements is dependent on the salt and carrier used. In the studies presented, the magnitude of the rise in plasma Ca concentration following administration of the Ca preparation was used as an index of Ca absorption by the gastrointestinal tract. Calcium chloride preparations in a water-soluble carrier (propylene glycol) were absorbed more readily than Ca propionate in propylene glycol, but Ca propionate effected a more sustained increase in plasma Ca concentration. Vegetable oil preparations of these salts were poorly absorbed. Calcium chloride preparations induced a significant decrease in blood and urine pH. Calcium propionate salts did not alter acid-base balance. Rectal administration of Ca salts could raise plasma Ca concentration rapidly, but caused serious pathological lesions, precluding their use.

Acid-Base Equilibrium↗

Calcium and vitamin D metabolism in the dairy cow.

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.

Animals↗