Materials and method Animals and blood samples

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1 Originl Reserch 1 / 12 Veterinri OA México Publicción Digitl de l Fcultd de Medicin Veterinri y Zootecni o Effect of prostglndin F2α dministrtion during the first postprtum hours on the serum clcium concentrtion of diry cows Eligio Gbriel Slgdo Hernández Jn Boud Adolfo Apricio Cecilio A Jroslv Doubek b Frncisco Hernny Velásquez Forero c* Deprtmento de Ptologí, Sección Ptologí Clínic, Fcultd de Medicin Veterinri y Zootecni, Universidd Ncionl Autónom de México, Av. Universidd 3000, Col. Cd. Universitri, México, D.F., México b Deprtment of Physiology, Fculty of Veterinry Medicine, University of Veterinry nd Phrmceuticl Sciences, Brno, Czech Republic c Lbortorio de Metbolismo Minerl y Óseo, Hospitl Infntil de México Federico Gómez Dr. Márquez 162, Col. Doctores, Del. Cuuhtémoc, 06720, México, D.F., Mexico *Corresponding uthor Tel.: ext. 4408/3401 Emil ddress: fcovelfor@gmil.com Abstrct Subclinicl hypoclcemi occurs frequently in diry cows nd predisposes them to reproductive pthologies. Prostglndin F2 (PGF2) improves uterine helth nd increses the level of serum clcitriol in other species. The im of this study ws to evlute the effect of sodium cloprostenol on serum clcium, metbolites of vitmin D nd reproductive vribles. Eighty multiprous Holstein cows were selected nd rndomized into two groups. The cows in Group 1 (n = 38) were treted with 500 µg of I M sodium cloprostenol, synthetic nlog of PGF2, t 1 nd 48 h postprtum. Group 2 ws the control group (n = 42). Blood smples were tken from 10 nimls per group t 1, 3, 12, 24, 48 h nd 7 d postclving. The incidence of retined plcent, metritis nd endometritis nd the number of open dys were recorded. The concentrtions of C, P, Mg, clcidiol nd clcitriol in the serum were evluted using n nlysis of vrince for repeted mesures design. The serum C concentrtion ws incresed up to normlized t dy 7 in the PGF2α group compred with the level in the control group. PGF2α tretment incresed the serum clcium concentrtion nd reduced the number of open dys, nd thus, could be useful in preventing subclinicl hypoclcemi nd postprtum reproductive problems. Keywords: Prostglndin F2; Subclinicl hypoclcemi; Clcitriol; Postprtum diry cow Received: Accepted: Published: Additionl informtion nd declrtions cn be found on pge 10 Copyright 2014 Eligio Gbriel Slgdo Hernández et l. open ccess Distributed under Cretive Commons CC-BY 4.0 Introduction Subclinicl hypoclcemi (SH) occurs minly during the first 48 hours postprtum in diry cows, the frequency of its occurrence increses in cows with higher prity (Reinhrdt et l., 2011). Some cows my suffer SH for longer period (Slgdo et l., 2014, b). Cows with serum clcium (C) concentrtions greter thn 2.1 mmol/l lso hve lower concentrtion of serum nonesterified ftty cids (NEFA), indicting tht SH predisposes the nimls to other energy-blnce problems (Reinhrtdt, 2011). Cows with SH, defined s serum C level of less thn 2.0 mmol/l in t lest one smple within the first 3 dys postprtum, presented higher concentrtions of ß-hydroxybutyrte (BHBA) nd NEFA postprtum, s well s higher incidence of metritis, lower pregnncy rte nd higher birth-conception

2 Effect of PGF2α on serum clcium of diry cows Originl Reserch 2 /12 intervl (Mrtinez et l., 2012). Subclinicl hypoclcemi, high concentrtions of BHBA nd NEFA nd deficiency in vitmin E, selenium nd other minerls decreses the strength of the immune system, which is required for the dequte delivery of the plcent (Kimur et l., 2006). Retention of fetl membrnes increses the risk of endometritis nd metritis, which negtively ffect vrious reproductive prmeters (Curtis et l., 1983, Mrtinez et l., 2012). Prostglndin F2 lph (PGF2α) plys n importnt role in the mechnism underlying the expulsion of the plcent fter clving, cows tht hd retined the plcent hd lower concentrtion of PGF2α in the cotyledons compred with tht of cows tht did not retined the plcent (Leidl et l., 1980). In nother study, it ws found tht the concentrtions of PGF2α nd prostglndin E1 (PGE1) incresed in the first hour postprtum in the cows tht did not retin the plcent (Wischrl et l., 2001). In contrst, ewes treted with inhibitors of prostglndin-synthesis during the erly postprtum period retined the plcent (Chssgne nd Brnouin, 1993). The mechnism by which prostglndins prevent plcentl retention nd improve uterine helth hs not been fully elucidted. It is believed tht incresed uterine contrction is fctor of the mechnism of ction. However, it hs lso been observed tht PGF2α incresed the phgocytic ctivity of neutrophils in the uterine mucos nd incresed the level of vrious cytokines tht stimulte immune function (Lewis nd Wulster-Rdcliffe, 2006), but this mechnism is not well understood. A syndrome in which PGE1 is over-produced hs been described in children; the ffected infnts hve hyperclciuri nd incresed levels of serum clcitriol nd C (Welch, 1997). Studies in rts hve shown tht the dministrtion of PGE2 incresed the synthesis of clcitriol (Ymd et l., 1983). Furthermore, it hs been demonstrted in rbbits, both in vitro nd in vivo, tht the dministrtion of PGE1 lso incresed the synthesis of clcitriol (Velásquez-Forero et l., 2006). In cultures of chicken kidney cells, both PGE1 nd PGF2α were observed to increse the rte of conversion of clcidiol to clcitriol (Treschel et. l., 1980). A deficiency in the synthesis or ctivity of clcitriol hs been described s one of the leding cuses of hypoclcemi in diry cows (Goff et l., 1989; Goff et l., 1991). To our knowledge, no studies hve exmined the effect of PGF2α tretment on clcitriol synthesis in cttle. It is likely tht prostglndin increses the concentrtion of serum clcitriol, which would hve positive effect on the serum C concentrtion in erly postprtum diry cows, which my prtilly explin the mechnism of ction of PGF2α on reproductive prmeters. The objective of this study ws to evlute the effect of prostglndin F2α dministrtion during the erly postprtum period on the levels of blood serum clcium, phosphorus, mgnesium nd the metbolites of vitmin D nd on the reproductive prmeters of diry cows. Mterils nd method Animls nd blood smples This study ws conducted on commercil frm with 3200 Holstein cows, with n nnul men milk production of kg/cow, locted ner the city of Torreon,

3 Effect of PGF2α on serum clcium of diry cows Originl Reserch 3 /12 Tble 1. Ingredients nd chemicl composition of preprtum nd postprtum diets Ingredient Preprtum Postprtum Corn silge, % Alflf hy, % Ots hy, % Ground corn, % Distillers grins, % 5.5 Soyben mel, % Sugrcne molsse, % 4.8 Cotton seed, % Cnol mel, % 4.5 Vitmin nd minerl premix, % Chemicl composition Dry Mtter, % CP, % NDF, % NEL, Mcl/kg DM C, % P, % Mg, % K, % N, % S, % Cl, % DCAD (meq/kg DM) CP = crude protein, NDF = neutrl detergent fiber, NEL = Net energy of lcttion, DCAD = dietry ction-nion difference using the formul: (N + K) - (Cl S) in milliequivlents per Kg of dry mtter. Cohuil, Mexico. The cows were mintined in the sme pen before nd fter clving, nd they received totl mixed rtion twice dily nd wter d libitum (Tble 1). Eighty multiprous cows with body condition score (BCS) of 3.25 to 3.5 t clving were selected nd were rndomly plced in one of two groups. Cows tht presented dystoci were excluded from the study. The cows in Group 1 (n = 38) were dministered the synthetic PGF2 nlog, sodium cloprostenol, i.m. t dose of 500 µg (in 2 ml) per niml t the first hour nd t 48 h fter clving. The dose nd frequency used ws bsed on previous work by Orteg et l. (2013). The cows in Group 2 (n = 42) did not receive ny tretment. Blood smples for serum preprtions were collected through til vein puncture in 7-mL vcuum tubes lcking nticogulnt (Monoject, Argtech, Inc., Mnfield, MA, USA) from ten cows in ech group before the dministrtion of PGF2 nd t 3, 12, 24, 48 hours nd 7 d fter tretment. Blood smples were centrifuged t 1200 g for 10 min within 1 h fter smpling. The serum smples were plced in plstic vils nd stored t -20 C until nlysis. The incidence of retined plcent, metritis nd endometritis nd the number of open dys were recorded. A retined plcent ws defined s plcent

4 Effect of PGF2α on serum clcium of diry cows Originl Reserch 4 /12 tht cow did not eliminte during the first 24 h postprtum. Metritis ws chrcterized s fetid brown-red vginl dischrge during the first 20 d postprtum, with clinicl signs of disese. Endometritis ws defined s the presence of purulent vginl secretion between 10 nd 50 d fter clving, without clinicl signs. All of the procedures were conducted ccording to the guidelines of the Institutionl Ethicl Committee on the Use nd Cre of Animls of the Fcultd de Medicin Veterinri y Zootecni (FMVZ), Universidd Ncionl Autónom de México (UNAM). Blood serum nlyses The serum concentrtions of C, P nd Mg were determined using colorimetric method (Rndox, Crumlin, UK) in semi-utomtic model Selectr Junior nlyzer (Vitl Scientific, Spnkeren, The Netherlnds) in the section of Clinicl Pthology of the Deprtment of Pthology (FMVZ, UNAM). The clcidiol nd clcitriol concentrtions were ssessed using rdioimmunossys fter I 125 lbeling ws performed (DiSorin, Stillwter, MN, USA) t the Federico Gómez Children s Hospitl in Mexico City. Sttisticl nlysis The levels of serum C, P, Mg, clcidiol nd clcitriol were ssessed using n nlysis of vrince for completely rndomized design with repeted mesurements fter verifiction of the homogeneity of vrince nd normlity (SPSS softwre version 10.0 for Windows). The effect of tretment ws the between-subjects fctor, nd the time of smpling ws the within-subjects interction, The Bonferroni djustment ws used post hoc to test for differences between mens.the cses of subclinicl hypoclcemi, retention of the plcent, metritis, nd endometritis were ssessed using test for the homogeneity of proportions nd one tiled Fisher exct test. The number of open dys ws evluted using Kpln-Meier survivl curve nd the differences between the curves were evluted using Log Rnk test (Medclc softwre, MedClc Sttisticl Softwre version ). Effects were considered significnt t P < Results Figure 1 shows serum concentrtion for C, P, nd Mg throughout the study. A timeby-tretment interction ws observed for the serum C level (P < 0.05). The serum C concentrtion incresed by dy 7 postprtum in the cows tht were treted with the synthetic PGF2 nlog compred with the controls (P < 0.05). The percentge of cows with subclinicl hypoclcemi is shown in Tble 2. There were no cses of prturient presis. The concentrtions of serum P nd Mg were not different in the two groups of cows nd were unchnged throughout the smpling period (P > 0.05). There were no differences between the treted nd control cows in serum clcidiol concentrtion (Fig. 2). For serum clcitriol, there ws time-by-tretment interction effect (P < 0.05, Fig. 2). The clcitriol concentrtion ws incresed t 48 h nd 7 d postprtum with respect to vlue t the first hour postprtum in the PGF2α-treted group (P < 0.05). In contrst, in the control group, the concentr-

5 Effect of PGF2α on serum clcium of diry cows Originl Reserch 5 / b C mmol/l h 3 h 12 h 24 h 48 h 7 d P mmol/l h 3 h 12 h 24 h 48 h 7 d Mg mmol/l h 3 h 12 h 24 h 48 h 7 d Time fter clving Figure 1. Serum C, P nd Mg concentrtions in diry cows treted with 500 µg of sodium cloprostenol t 1 nd 48 hours postprtum (n = 10) nd in control cows (n = 10) (men vlues ± SD). There ws time- by-tretment interction for the C vlues (P < 0.05). Different letters indicte significnt difference from the control group t the sme time of smpling, determined using the Bonferroni djustment (P < 0.05).

6 Effect of PGF2α on serum clcium of diry cows Originl Reserch 6 /12 Tble 2. Proportion (percentge) of cses of subclinicl hypoclcemi (serum C < 2.0 mmol/l) observed in control Holstein diry cows vs those treted with 500 µg of sodium cloprostenol t different times postclving. Postclving time Group of cows 1 h 3 h 12 h 24 h 48 h 7 d (n = 10) 8/10 (80%) (n = 10) 8/10 80% 8/10 (80%) 4/10 (40%) 7/10 (70%) 6/10 (60%) 8/10) (80%) 6/10 (60%) 8/10 (80%) (4/10) 40% 6/10 (60%) 1/10 (10%) P vlue tion of serum clcitriol ws incresed t 24 nd 48 hours fter clving compred with the vlue t the first smpling; however, t 7 dys postprtum, the level hd returned to the originl vlue (P < 0.05) (Fig. 2). The number of cses of retined plcent (P = 0.15), metritis (P= 0.15) nd endometritis (P = 0.8) in the two groups were not different (Fig. 3). The men nd medin numbers of open dys were ± 4.4 nd 98, respectively in the sodium cloprostenol-treted group nd ± 4.9 nd in the control group. Anlysis of the survivl curves showed significnt effect of the tretment (P = 0.02; Fig. 4). Discussion The increse in serum C concentrtion in the cows tht were treted with PGF2α is the expected result, bsed on studies in rts, rbbits nd chickens, s well s in children with the syndrome of prostglndin E over-production (Welch, 1997). To the uthors knowledge, there is no previous study in cows on the effect of PGF2α on the serum C level with which to compre these results. In some studies conducted with rts treted with PGE2 (Ymd et l., 1983) or rbbits treted with PGE1 (Velásquez-Forero et l., 2006) nd in children with the PGE1 over-production syndrome, the serum clcitriol level nd the urinry excretion of C incresed, wheres the serum C concentrtion ws stble. However, the serum C concentrtion incresed in vivo in study of rbbits treted with PGE1 (Veláquez-Forero et l., 2006); the discrepncy between these results my lie in the different concentrtions of the prostglndin compounds used, the specific needs of ech species, the dose nd the frequency of ppliction of the prostglndin. In this study of cows with subclinicl hypoclcemi, n increse in the serum clcium concentrtions t 7 dys postprtum ws observed in the cows tht were treted with PGF2α. As shown in Tble 2, the number of cses of subclinicl hypoclcemi ws lower (P < 0.03) t 7 dys postprtum in the cows treted with PGF2α thn in untreted cows, nd t 3 nd 48 hours postprtum there ws tendency (P = 0.08) for lower number of cses of subclinicl hypoclcemi in the PGF2α-treted cows thn in untreted cows. These results support the positive effect of PGF2α on serum C, lthough more cows nd higher doses re needed for better evlution. The increse in serum C levels in the PGF2α-treted cows ws observed t dy 7 postprtum. In order to chieve this effect in more timely mnner, PGF2α could

7 Effect of PGF2α on serum clcium of diry cows Originl Reserch 7 / d Clcitriol pmol/l c b b b bc bc b b b b 1 h 3 h 12 h 24 h 48 h 7 d Clcidiol nmol/l h 3 h 12 h 24 h 48 h 7 d Time fter clving Figure 2. Serum clcitriol nd clcidiol concentrtions in diry cows treted with 500 µg of sodium cloprostenol t 1 nd 48 hours postprtum (n = 10) nd in controls (n = 10) (men vlues ± SD). For clcitriol, there ws tretment-by-time interction (P < 0.05). Different letters indicte significnt difference between the men vlues, s determined using the Bonferroni djustment (P < 0.05). be dministered severl dys preprtum, but its negtive effect on plcentl retention mkes it necessry to strt tretment only fter clving. The serum concentrtions of phosphorus (P) nd mgnesium (Mg) were unffected by the tretment. This result is very interesting becuse, physiologiclly, serum P concentrtions decrese when C concentrtions re low (Kojouri, 2003), wheres in this study, the concentrtion of P did not decrese even though hypoclcemi developed in cows. This phenomenon occurs when hypoclcemi stimultes prthyroid hormone (PTH) production nd this hormone stimultes n exchnge mechnism in the kidney by which it retins C nd secretes P, cusing decrese in the P concentrtion in the blood, s well s secretion of both minerls into the colostrum (Kojouri, 2003). Recently, Fibroblst Growth Fctor-23 (FGF-23) hs been described s n importnt regultor of P metbolism, so tht when the

8 Effect of PGF2α on serum clcium of diry cows Originl Reserch 8 / Percent of cses Plcent retention Metritis Endometritis Figure 3. Percentge of cses of plcent retention, metritis nd endometritis in diry cows treted with 500 µg of cloprostenol sodium t 1 nd 48 h postprtum (n = 38) nd in controls (n = 42). 100 Percent of pregnnt Dys postprtum Figure 4. Cumultive percentge of conception in diry cows treted with 500 µg of sodium cloprostenol t 1 nd 48 h postprtum (n = 38) nd in controls (n = 42). The curves re significntly different (P = 0.02), s determined using the Log Rnk test. P level increses, the secretion of FGF-23 lso increses. FGF-23 inhibits PTH synthesis nd ctivtes 1α-hydroxylse enzyme (1α-OHse), which is necessry to convert clcidiol into clcitriol (Shimd et l., 2004); t the level of the prthyroid glnd, elevtion in the concentrtion of clcitriol lso inhibits PTH synthesis, s demonstrted by study of cultured bovine prthyroid cells (Krjisnik et l., 2007). In contrst, in the kidney, FGF-23 inhibits 1α-OHse, nd s result, clcitriol production decreses (Fukumoto nd Ymshit, 2002). In this study, there ws no decrese in the serum P level; in contrst, it ws observed tht the P concentrtion incresed slightly t 12 nd 24 h postprtum in the group treted

9 Effect of PGF2α on serum clcium of diry cows Originl Reserch 9 /12 with PGF2α. The mechnism through which this occurred is difficult to explin becuse the clcitriol concentrtion ws higher in the control group t 12 nd 24 hours postprtum. The level of clcitriol incresed t 24 nd 48 hours fter clving in the control group, which is contrry to the expected results. In chicken kidney cell cultures, PGE1 nd PGF2α hve been shown to increse the levels of clcitriol (Treschel et l., 1980). In rbbits, both in vitro nd in vivo, dily dministrtion of PGE1 for 20 dys incresed the rte of conversion of clcidiol to clcitriol (Velásquez-Forero et l., 2006). The results of this experiment do not support the hypothesis tht PGF2α incresed the level of serum clcitriol in diry cows, t lest t the dose nd frequency used. Further reserch using higher doses nd greter frequency of PGF2α dministrtion is needed. The clcidiol concentrtions were similr in the two groups t ll of the smpling times, which indicted tht the tretment did not ffect the metbolism of this precursor of clcitriol. It is not possible to compre this result to others becuse, to the uthor s knowledge, there re no reports in the literture mentioning ny effect of PGF2α or PGE1 on clcidiol synthesis in cttle or in other species. Recently, the norml serum clcidiol concentrtions in humns hve been discussed, lthough this vlue is not well defined. The serum clcidiol concentrtion of the diry cows in this study ws greter thn the norml concentrtions reported for humns. Although there re no studies on the norml vlues for diry cows, the high incidence nd exposure to solr rdition in the region where this study ws conducted suggests tht the nimls do not hve deficiency of clcidiol (Slgdo et l., 2014). Furthermore, the dose of PGF2α used hs been commonly used to tret uterine diseses nd to induce luteolysis. However, Treschel et l. (1980) observed dose-dependent response in cultures of chicken tubulr kidney cells. It is necessry to determine whether higher doses or greter frequency of ppliction could trigger response to clcitriol in cows. Another possible mechnism for why the incresed serum C concentrtion did not decrese the serum P concentrtion during the first postprtum hours in the cows tht were treted with PGF2α, despite their hving lower serum clcitriol concentrtions, could be the presence of n elevted number of vitmin D receptors (VDRs), which would increse the efficiency of the effect of clcitriol on the intestinl bsorption of C nd P. Humns with idiopthic hyperclciuri were shown to hve norml clcitriol concentrtions; however, they hd incresed intestinl uptke of C nd the hyperclciuri ws found to be due to the incresed expression of VDRs (Fvus et l., 2004). The primry fctors tht stimulte the expression of these receptors re clcium nd clcitriol (Crrillo-Lopez et l., 2009), so tht slight increse in the concentrtions of clcitriol nd C fter the ppliction of PGF2α could result in the greter efficiency on the ctions of clcitriol. Studies designed to exmine whether these chnges occur in diry cows re needed to fcilitte understnding of the mechnism of ction of PGF2α nd demonstrte with greter certinty the usefulness of PGF2α tretment to prevent hypoclcemi. The number of cses of plcentl retention, metritis nd endometritis of the two groups were not different, lthough numericlly better performnce ws observed in the cows in the treted group. This result could be due to the number of nimls tht were used for this study becuse Orteg et l. (2012) performed study using lrger number of nimls (n = 180) nd found significnt differences between the nimls tht were treted or not treted, with numericl results similr to those

10 Effect of PGF2α on serum clcium of diry cows Originl Reserch 10 /12 of this study. The use of PGF2α in the erly hours postprtum is controversil; its mechnism of ction hs been thought to be cusing the lysis of the corpus luteum, which cuses decrese in the progesterone levels (Lnder Chcin et l. 1990). However, in the erly dys postprtum, the cows hve no corpus luteum upon which PGF2α could ct. In study of intct nd ovriectomized sheep treted with exogenous progesterone, it ws observed tht uterine susceptibility to experimentl chllenge with Arcnobcterium pyogenes nd E. coli ws lower in ewes treted with PGF2α regrdless of the bsence or presence of progesterone; so it is believed tht PGF2α hs direct immune-modultory effects (Lewis et l., 2006). The increse in serum C concentrtions cused by the ctivity of PGF2α, in ddition to the direct ction of PGF2α, could prtilly explin the positive effects of the immune system nd the prevention of metritis nd plcentl retention observed in some studies. The dministrtion of sodium cloprostenol incresed the cumultive curve of pregnnt cows in this experiment. Orteg et l. (2012) showed tht the ppliction of sodium cloprostenol t 12 nd 48 hours postprtum decresed the incidence of plcentl retention, shortened the intervl from prturition to first estrus nd incresed the pregnncy rte s evluted t 90 dys postprtum; these findings re similr to our results. The mechnism by which PGF2α hd positive effects on reproduction in this study is difficult to explin. A positive effect of PGF2α in the tretment of metritis ws observed by Melendez et l. (2004). Most likely, the effect of PGF2α on the immune system improved uterine helth nd fertility (Lewis et l., 2006). Conclusions In this study, the dministrtion of PGF2α t the first hour nd t 48 hours fter clving incresed the serum C level nd decresed the number of cses of subclinicl hypoclcemi t dy 7 postprtum. It lso reduced the number of open dys in diry cows. Therefore, this tretment could be used to prevent reproductive problems in diry cows. Funding This study ws funded by Universidd Ncionl Autónom de México, reserch project PAPIIT IN Acknowledgments The uthors re indebted to Prof. Jesse P. Goff, D.V.M, PhD, from Iow Stte University, for the revision of this mnuscript. Conflicts of interest The uthors declre tht they hve no conflicts of interest. Author contributions Eligio Gbriel Slgdo Hernández: Designed the experiment, conducted field work, performed lbortory nd sttisticl nlyses, interpreted the results, nd prepred the mnuscript.

11 Effect of PGF2α on serum clcium of diry cows Originl Reserch 11 /12 Jn Boud: Designed the experiment, performed lbortory nd sttisticl nlyses, interpreted the results, nd prepred the mnuscript. Adolfo Apricio Cecilio A.: Designed the experiment, conducted field work, nd reviewed the mnuscript. Jroslv Doubek: Designed the experiment, interpreted the results, nd reviewed the mnuscript. Frncisco Hernny Velásquez Forero: Designed the experiment, nlyzed nd interpreted the results of vitmin D metbolites, nd reviewed the mnuscript. References 1) Crrillo-López N, Fernández-Mrtin JL, Cnnt-Andí JB Ppel del clcio, clcitriol y sus receptores en l regulción de l prtiroides. Nefrologí. 29 (2): ) Chssgne M, Brnouin J The effect of inhibition of prostglndin F2 lph synthesis on plcentl expulsion in the ewe. Cndin Journl of Veterinry Reserch. 57 (2): ) Curtis CR, Erb HN, Sniffen CJ, Smith RD, Powers PA, Smith MC, White ME, Hillmn RB, Person EJ Assocition of prturient hypoclcemi with eight periprturient disorders in Holstein cows. Journl of Americn Veterinry Medicl Assocition. 183 (5): ) Fvus MJ, Krnusks AJ, Prks JH, Coe LF Peripherl blood monocyte vitmin D receptor levels re elevted in ptients with idiopthic hyperclciuri. Journl of Clinicl Endocrinology nd Metbolism. 89 (10): ) Fukumoto S, Ymshit T Fibroblst growth fctor-23 is the phosphturic fctor in tumor-induced osteomlci nd my be phosphtonin. Current Opinion in Nephrology nd Hypertension. 11 (4): ) Goff JP, Reinhrdt TA, Horst RL Recurring hypoclcemi of bovine prturient presis is ssocited with filure to produce 1.25 dihydroxyvitmin D. Endocrinology, 125 (1): ) Goff JP, Reinhrdt TA, Horst RL Enzymes nd fctors nd ction in norml controlling vitmin D metbolism nd milk fever cows. Journl of Diry Science. 74 (12): ) Kimur K, Reinhrdt TA, Goff JP Prturition nd hypoclcemi blunts clcium signls in immune cells of diry cttle. Journl of Diry Science. 89 (7): ) Kojouri GHA Prturient presis nd its reltionship with hypophosphtemi (bstrct). Act Veterinri Scndinvic, Supplementum. 98: ) Krjisnik T, Bjorklund P, Mrsell R, Ljunggren O, Akerstrom G, Jonsson JB, Westin G, Lrsson TE Fibroblst growth fctor-23 regultes prthyroid hormone nd 1lph hydroxylse expression in cultured bovine prthyroid cells. Journl of Endocrinology. 195 (1): ) Lnder-Chcin MF, Hnsen PJ, Drost M Effects of stge of the estrous cycle nd steroid tretment on uterine immunoglobulin content nd polymorphonucler leukocytes in cttle. Theriogenology. 34(6): ) Leidl W, Hegner D, Rockel P Investigtion on the PGF2 concentrtion in the mternl nd fetl cotyledons of cows with nd without retined fetl membrnes. Zentrlbltt für Veterinärmedizin Reihe A. 27 (9-10):

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