During early lactation dairy cows often experience health disorders, which are usually associated with decreased production and reproduction variables. Following parturition, cows use more energy for maintenance and milk production than they consume and enter into a state of negative energy balance. Negative energy balance in early lactation is thought to contribute to decreased milk production, reduced reproductive performance, and increased health disorders. Flunixin meglumine (FM) is an anti-pyretic (fever reducing) and anti-inflammatory drug that is commonly used in the dairy industry. This study evaluated the effect of FM on pyrexia, production and bioenergetic variables in postparturient dairy cows.

In zwei Kälberbeständen wurde die therapeutische Wirksamkeit des Breitband-Antibiotikums Florfenicol mit und ohne zusätzliche Kombination des nichtsteroidalen Antiphlogistikums Flunixin-Meglumin bei der Behandlung von bovinen Respirationskrankheiten getestet. Anhand von bakteriologischen und serologischen Untersuchungsbefunden werden die jahreszeitlichen sowie altersabhängigen Beziehungen zwischen der Tiergesundheit, dem Nachweis bakterieller Infektionserreger, C-reaktivem Protein, Anti-Lipid A-Antikörpern und dem Gehalt an Endotoxin aufgezeigt. Florfenicol erwies sich aufgrund seines mikrobiologischen Profils sowie seiner Wirksamkeit für die Behandlung der Enzootischen Bronchopneumonie als gut geeignet. Flunixin-Meglumin stellt hinsichtlich seiner analgetischen, antipyretischen und antiphlogistischen Eigenschaften eine sinnvolle und sichere Ergänzung zur antibiotischen Therapie bei bovinen Respirationserkrankungen dar.

Doctor of Philosophy / Department of Anatomy and Physiology / Johann F. Coetzee / Flunixin meglumine has been used as an antipyretic and anti-inflammatory since the 1980s. In 2013, a novel formulation was released in the European Union for topical administration and transdermal absorption. Approval for transdermal flunixin in cattle in the United States occurred in 2017, and included a label claim for the control of pain associated with infectious pododermatitis (foot rot). This new formulation allows for needle-less delivery of flunixin with minimal restraint and training required. In this dissertation, the pharmacokinetics of transdermal flunixin in Holstein calves at 2 months of age and adult lactating cows is described. In these pharmacokinetic studies, plasma flunixin concentrations were determined using high-pressure liquid chromatography coupled with mass spectroscopy. Pharmacokinetic modeling was completed using non-compartmental modeling methods using a commercially available computer program. Ex vivo prostaglandin E₂ (PGE₂) production using a whole blood model served as a biomarker for the anti-inflammatory effects of flunixin meglumine and suppression of cyclo-oxygenase enzyme-2. The concentrations of PGE₂ were determined using a commercially available enzyme-linked immunosorbent linked assay (ELISA) kit. The effects of age and pain on the pharmacokinetics of flunixin were investigated. Both influenced the pharmacokinetics and anti-inflammatory effects of flunixin. Cautery dehorning without local anesthetic was used in the calf model to generate pain. The pain associated with dehorning caused lower absorption of the transdermal flunixin and a longer terminal half-life. This longer half-life did result in lower PGE₂ concentrations at later time points. The influence of age was determined in the same group of Holstein calves at 2 months and 8 month of age. Age related effects included lower clearance, a longer half-life, and longer suppression of PGE₂ following intravenous injection. Following transdermal administration, older animals had a prolonged absorption leading to a longer half-life and apparent ‘flip-flop’ pharmacokinetics. Additionally, the suppression of PGE₂ was not observed in older calves following transdermal flunixin administration. The analgesic properties of transdermal flunixin were tested using three different pain models. Those pain models include cautery dehorning, surgical castration, and induced lameness. The reduction in plasma cortisol following transdermal administration was the most consistent finding in each model for pain. Infrared thermography (IRT) was used to assess either activation of the autonomic nervous system or local inflammation. Flunixin did not have any effects on substance P concentration in all three pain models. Gait analysis using a floor based pressure mat was used in the assessment of castration and lameness pain. Although there were no observed effects of flunixin in those studies, the use of this technology for pain assessment is promising. Future studies of transdermal flunixin to determine its utility as part of a multi-modal analgesic plan are still warranted. Specifically, the use a of a local anesthetic block at the time of cautery dehorning, as flunixin has minimal effects on pain, and its pharmacokinetics were altered by the painful stimulus. Timing of the dose relative to the painful procedure is also needed as flunixin is rapidly absorbed. Field studies in lame cattle are needed as there is a deficiency in the literature as only models of lameness induction have been reported.

The objectives of this study were to evaluate the effects of flunixin meglumine (FM), an inhibitor of PGF2a synthesis, administered at the time of embryo transfer (ET) and insertion of an intravaginal progesterone-releasing device (CIDR) at the time of ET on pregnancy rates (PR) and the resynchronization of estrus. Beef cows (n = 796) and heifers (n = 108) at three locations were assigned randomly within age to one of four groups in a 2 x 2 factorial arrangement of treatments with injection of FM (500 mg i.m.; Phoenix Scientific, St. Joseph, MO) 2 to 12 min prior to ET and insertion of a CIDR (1.38 g progesterone; Pfizer, New York, NY) for 13 d immediately following ET as main effects. Fresh or frozen embryos (Stage = 4 or 5; Grade = 1 or 2) were randomly assigned to be transferred to recipients on d 6 to 9 of the estrous cycle. At Location 2 a subset of fresh embryos were split and transferred as fresh half embryos (n = 192). Recipients at Location 2 only (n = 493) were observed for signs of return to estrus beginning 9 d after ET. Recipients that returned to estrus at Location 2 were either bred by AI 12 h after estrus or received an embryo 7 d after estrus. Pregnancy was diagnosed by ultrasonography. Pregnancy rates were analyzed using the LOGISTIC procedure of SAS. Pregnancy rates of split embryo recipients were analyzed separately using the same statistical procedure. Variation in the timing of the return to estrus was determined by an F-test for heterogeneity of variances. Following the initial ET, pregnancy rates of recipients receiving whole embryos were not affected by CIDR administration (P > 0.05; 65% with CIDR, 70% without CIDR), however, there was a significant FM x location interaction on PR (Location 1, 89 vs. 57%; Location 2, 69 vs. 64%; Location 3, 64 vs. 67% for FM vs. no FM, respectively). There was a significant CIDR x FM interaction on PR of recipients receiving split embryos. Pregnancy rates of split embryo recipients receiving CIDR treatment (54%) or FM treatment alone (41%) were less than controls (64%). However, recipients receiving both CIDR and FM had PR similar to controls (60%). The timing of the return to estrus was more synchronous (P < 0.01) for recipients fitted with a CIDR, but PR of recipients bred following a return to estrus did not differ in cows receiving or not receiving a CIDR (P > 0.13; 68 and 62%, respectively). Effects of FM on PR were location dependent and CIDR insertion at ET improved synchrony of the return to estrus. / Master of Science

Problemstellung: Der Motilität und Entleerung des Labmagens und dem antioxidativen Status wird im Zusammenhang mit Labmagenverlagerungen eine große Bedeutung beigemessen. Zu den häufigsten Komplikationen im post¬operativen Zeitraum zählen Entleerungsstörungen und mangelnde Motilität des Labmagens. Bisher existieren aber kaum Untersuchungen über die Beeinflussbarkeit dieser Probleme. Zielstellung: In der folgenden Untersuchung sollte geprüft werden, wie die Medikamente Neoancemin® und Flunixin-Meglumin die klinische Rekonvaleszenz, die Entleerung des Labmagens, den antioxidativen Status und ausgewählte klinisch-chemische Parameter in den ersten 24 Stunden nach der Reposition des Labmagens beeinflussen. Material und Methoden: Die Studie umfasst 45 Kühe aus dem Patientengut der Medizinischen Tierklinik mit linksseitiger Labmagenverlagerung (LDA). Diese stammten aus milcherzeugenden Betrieben im Leipziger Umland und gehörten zur Rasse Holstein-Schwarzbunt. Die Kühe wurden wegen einer bestehenden LDA zur Operation und Nachbehandlung eingewiesen. Die Kühe wurden jeweils bei Klinikeinweisung und Diagnosestellung abwechselnd einer der drei Gruppen zugeordnet. Gruppe 1: 15 Kühe erhielten 2,2 mg/kg Flunixin-Meglumin 2h präoperativ Gruppe 2: 15 Kühe erhielten 7 ml/100 kg Neoancemin® (Chlorpheniramin 12,5 mg/ml, Ascorbinsäure 100 mg/ml, Thiaminchlorid-HCl 10 mg/ml, Glucose 100 mg/ml, Fa. Inropharm, Fürstenzell) 2h präoperativ Gruppe 3: 15 Kühe, ohne Behandlung, Kontrollgruppe Beide Medikamente wurden intravenös verabreicht. Zwei Stunden nach dieser Prämedikation erfolgte die operative Reposition des Labmagens mittels Omento¬pexie in der rechten Flanke. Die Labmagenentleerung wurde mit Hilfe des Monosaccharids D-Xylose erfasst. Dieses wurde im Rahmen der Operation in einer Dosis von 0,5g/kg KM (50%ige Lösung) in den Labmagen eingebracht. Über die Darstellung der D-Xylose-Konzentration im Serum bis 12 h nach der Operation konnte eine indirekte Messung der Labmagenentleerung vorgenommen werden. Zur Charakterisierung des antioxidativen Status wurden die Enzyme Superoxid¬dismutase (SOD), Glutathionperoxidase (GPX) und die Trolox equivalent antioxidative capacity (TEAC) untersucht. Zur Beurteilung der klinischen Rekonvaleszenz wurden die Futteraufnahme, das Wiederkauverhalten, die Pansenmotorik, sowie Puls, Atemfrequenz und innere Körpertemperatur überwacht. Ergebnisse: Die mit Neoancemin behandelten Kühe zeigten eine deutlich schnellere Labmagenentleerung als die der Kontrollgruppe. Hier war die maximale Konzentration der D-Xylose im Blut (cmax ) im Mittel bereits nach 3,67 Stunden (tmax) erreicht. Bei den mit Flunixin-Meglumin behandelten Tieren lag tmax bei 4,07 Stunden, bei den Kühen der Kontrollgruppe bei 4,83 Stunden. Bei sechs der mit Neoancemin behandelten Kühe lag tmax sogar bei 1,5 Stunden, was dem Wert gesunder Kühe entspricht. Ein ähnliches Bild zeigten die klinischen Parameter. Hier ergaben sich, insbesondere bei den mit Flunixin-Meglumin behandelten Tieren, deutliche positive Effekte. In den Untersuchungen zum antioxidativen Status waren nur Tendenzen zu erkennen. Während die TEAC in der Kontrollgruppe abfiel, stieg sie in den Gruppen der behandelten Kühe an. Die GPX-Aktivität zeigte in der Kontrollgruppe einen deutlichen Anstieg, blieb aber in beiden Medikamentengruppen nahezu konstant. Bei Creatinkinase und Haptoglobin zeigten sich keine signifikanten Unterschiede zwischen den drei Gruppen. Schlussfolgerungen: Aufgrund der Ergebnisse ist es empfehlenswert, zwei Stunden vor der Reposition des nach links verlagerten Labmagens eine Prämedikation mit Neoancemin® oder Flunixin-Meglumin vorzunehmen.

Manipulation of the reproductive tract results in increased levels of prostaglandin, which may, in turn, reduce pregnancy rates in embryo recipients. Administration of a prostaglandin inhibitor prior to embryo transfer improves pregnancy rates in cows. Embryo transfer into heifers is more difficult and often requires additional manipulation of the uterus. This study was designed to determine whether administration of the prostaglandin inhibitor, flunixin meglumine, immediately prior to embryo transfer increases pregnancy rates in heifers. Heifers (n=466) were divided into two equal groups based on BCS (range=6-7) and weight (range=256-455). Estrus was synchronized in heifers by giving two injections of prostaglandin F_2" (PGF) eleven days apart with a two day stagger between groups. Heifers in each group were watched for estrus for four days following the second PGF injection. Each heifer detected in estrus (n~389; 83%) was palpated seven days later for the presence and location of an acceptable corpus luteum; development of the reproductive tract (uterine tract score; 1=prepubertal, 5=mature tract) and amount of uterine tone (uterine tone score; l=high tone, 2=medium tone, 3=low tone) were also estimated. The 352 heifers that had an acceptable CL were paired based on day of detected estrus, body condition score, body weight, and uterine tone score. One heifer of each pair was randomly assigned to receive 10ml of flunixin meglumine (IM) just prior to embryo transfer. Time between injection until completion of embryo transfer ranged from 2-25 minutes. All heifers received a single frozen/thawed embryo transferred by one of two experienced technicians. Data collected at the time of transfer included cervix score (1-3; 1=easily penetrated, 3=difficult), ease of transfer score (1-3; l=gun easily manipulated to site of transfer, 3=difficult), embryo placement in the uterine horn (U=upper 1/3, M=middle 1/3, L=lower 1/3), and technician. Pregnancy results were obtained 90 days after transfer via rectal palpation. The logistics procedures and chi-square analysis of SAS were used for data analysis.

Master of Science / Department of Animal Sciences and Industry / John Jaeger / Cattle grazing dormant native range (< 7% crude protein; CP) require supplementation of additional protein to sustain body weight (BW) and body condition score (BCS). Daily delivery of these supplements is an economic burden to cattle producers faced with challenging economic circumstances. Supplementing cows infrequently (as little as once/week) has produced equivalent BW and BCS changes compared to daily delivery. Dried distiller’s grains with solubles (DDGS) provides more ruminally-undegradable protein (RUP; 50-60%) compared to traditional oilseed-meal supplements (i.e. soybean meal) that are >50% ruminally-degradable protein (RDP). Therefore, our objective was to evaluate the effects of supplementation frequency on performance, reproductive success, eating behavior, and subsequent calf performance of spring-calving cows supplemented with DDGS. No differences in ending BW (P = 0.69) and BCS (P = 0.49), or changes in BW and BCS over the supplementation period (P = 0.82 and 0.70, respectively) were observed among cows supplemented every d, every 3 d, or every 6 d. Calf BW at birth, weaning weight (WW), and average daily gain (ADG) were similar among treatments (P = 0.19, 0.12, and 0.10, respectively). First-service conception rate (FSCR) and final pregnancy rate (PR) were also not affected by supplementation frequency (P = 0.62 and 0.76, respectively). The development of replacement heifers is a large expense for cow-calf producers. Improved breeding and heifer development strategies aimed at ensuring the success of replacement females have been developed but reproductive failure still remains a problem. The stress associated with breeding and handling procedures may decrease reproductive success. Therefore, the objective was to determine if intramuscular administration of flunixin meglumine (1.1 mg/kg BW) 14 days post-breeding would improve FSCR and PR in non-transported replacement heifers. Under the conditions of our study, flunixin meglumine did not improve (P = 0.87) first service conception rate above that of control heifers (41.2% and 42.3%, respectively). Final pregnancy rate also was not different between treatments and averaged 81.8% (P = 0.40).

Problemstellung: Der Motilität und Entleerung des Labmagens und dem antioxidativen Status wird im Zusammenhang mit Labmagenverlagerungen eine große Bedeutung beigemessen. Zu den häufigsten Komplikationen im post¬operativen Zeitraum zählen Entleerungsstörungen und mangelnde Motilität des Labmagens. Bisher existieren aber kaum Untersuchungen über die Beeinflussbarkeit dieser Probleme. Zielstellung: In der folgenden Untersuchung sollte geprüft werden, wie die Medikamente Neoancemin® und Flunixin-Meglumin die klinische Rekonvaleszenz, die Entleerung des Labmagens, den antioxidativen Status und ausgewählte klinisch-chemische Parameter in den ersten 24 Stunden nach der Reposition des Labmagens beeinflussen. Material und Methoden: Die Studie umfasst 45 Kühe aus dem Patientengut der Medizinischen Tierklinik mit linksseitiger Labmagenverlagerung (LDA). Diese stammten aus milcherzeugenden Betrieben im Leipziger Umland und gehörten zur Rasse Holstein-Schwarzbunt. Die Kühe wurden wegen einer bestehenden LDA zur Operation und Nachbehandlung eingewiesen. Die Kühe wurden jeweils bei Klinikeinweisung und Diagnosestellung abwechselnd einer der drei Gruppen zugeordnet. Gruppe 1: 15 Kühe erhielten 2,2 mg/kg Flunixin-Meglumin 2h präoperativ Gruppe 2: 15 Kühe erhielten 7 ml/100 kg Neoancemin® (Chlorpheniramin 12,5 mg/ml, Ascorbinsäure 100 mg/ml, Thiaminchlorid-HCl 10 mg/ml, Glucose 100 mg/ml, Fa. Inropharm, Fürstenzell) 2h präoperativ Gruppe 3: 15 Kühe, ohne Behandlung, Kontrollgruppe Beide Medikamente wurden intravenös verabreicht. Zwei Stunden nach dieser Prämedikation erfolgte die operative Reposition des Labmagens mittels Omento¬pexie in der rechten Flanke. Die Labmagenentleerung wurde mit Hilfe des Monosaccharids D-Xylose erfasst. Dieses wurde im Rahmen der Operation in einer Dosis von 0,5g/kg KM (50%ige Lösung) in den Labmagen eingebracht. Über die Darstellung der D-Xylose-Konzentration im Serum bis 12 h nach der Operation konnte eine indirekte Messung der Labmagenentleerung vorgenommen werden. Zur Charakterisierung des antioxidativen Status wurden die Enzyme Superoxid¬dismutase (SOD), Glutathionperoxidase (GPX) und die Trolox equivalent antioxidative capacity (TEAC) untersucht. Zur Beurteilung der klinischen Rekonvaleszenz wurden die Futteraufnahme, das Wiederkauverhalten, die Pansenmotorik, sowie Puls, Atemfrequenz und innere Körpertemperatur überwacht. Ergebnisse: Die mit Neoancemin behandelten Kühe zeigten eine deutlich schnellere Labmagenentleerung als die der Kontrollgruppe. Hier war die maximale Konzentration der D-Xylose im Blut (cmax ) im Mittel bereits nach 3,67 Stunden (tmax) erreicht. Bei den mit Flunixin-Meglumin behandelten Tieren lag tmax bei 4,07 Stunden, bei den Kühen der Kontrollgruppe bei 4,83 Stunden. Bei sechs der mit Neoancemin behandelten Kühe lag tmax sogar bei 1,5 Stunden, was dem Wert gesunder Kühe entspricht. Ein ähnliches Bild zeigten die klinischen Parameter. Hier ergaben sich, insbesondere bei den mit Flunixin-Meglumin behandelten Tieren, deutliche positive Effekte. In den Untersuchungen zum antioxidativen Status waren nur Tendenzen zu erkennen. Während die TEAC in der Kontrollgruppe abfiel, stieg sie in den Gruppen der behandelten Kühe an. Die GPX-Aktivität zeigte in der Kontrollgruppe einen deutlichen Anstieg, blieb aber in beiden Medikamentengruppen nahezu konstant. Bei Creatinkinase und Haptoglobin zeigten sich keine signifikanten Unterschiede zwischen den drei Gruppen. Schlussfolgerungen: Aufgrund der Ergebnisse ist es empfehlenswert, zwei Stunden vor der Reposition des nach links verlagerten Labmagens eine Prämedikation mit Neoancemin® oder Flunixin-Meglumin vorzunehmen.

In zwei Kälberbeständen wurde die therapeutische Wirksamkeit des Breitband-Antibiotikums Florfenicol mit und ohne zusätzliche Kombination des nichtsteroidalen Antiphlogistikums Flunixin-Meglumin bei der Behandlung von bovinen Respirationskrankheiten getestet. Anhand von bakteriologischen und serologischen Untersuchungsbefunden werden die jahreszeitlichen sowie altersabhängigen Beziehungen zwischen der Tiergesundheit, dem Nachweis bakterieller Infektionserreger, C-reaktivem Protein, Anti-Lipid A-Antikörpern und dem Gehalt an Endotoxin aufgezeigt. Florfenicol erwies sich aufgrund seines mikrobiologischen Profils sowie seiner Wirksamkeit für die Behandlung der Enzootischen Bronchopneumonie als gut geeignet. Flunixin-Meglumin stellt hinsichtlich seiner analgetischen, antipyretischen und antiphlogistischen Eigenschaften eine sinnvolle und sichere Ergänzung zur antibiotischen Therapie bei bovinen Respirationserkrankungen dar.

Made available in DSpace on 2014-08-20T14:37:56Z (GMT). No. of bitstreams: 1 dissertacao_viviane_rabassa.pdf: 236038 bytes, checksum: 5cfc0f0e2ed580d8304a3d1d8257390c (MD5) Previous issue date: 2007-02-05 / The artificial insemination (AI) with frozen semen in sheep is limited by the high costs of the laparoscopic technique and the variability of the results obtained from transcervical technique. This technique requires attachment of cervix, a procedure that can cause located injuries, further, the extensive uterine manipulation, which can lead to an exacerbated endometrial prostaglandin synthesis, could modify the uterine environment at the moment of conception. The objective of this study was to compare the efficiency of transcervical AI, through the technique of cervix attachment and retraction, in comparison to laparoscopic AI, as well as, to determine the effect of flunixin meglumine application at the moment of AI, on pregnancy rate of ewes, using frozen semen. In fixed-time inseminated ewes, during seasonal anestrous, there was no difference in the pregnancy rate between the transcervical and laparoscopic techniques, which was 40%. In respect to flunixin meglumine, the experiment was carried out during the breeding season and was performed using AI with estrus detection. There was no difference in the pregnancy rate between ewes receiving or not flunixin meglumine (p>0.05), which was 68.9% for the control group and 60.0% for the group that received flunixin meglumine at the moment of transcervical AI. These results were probably due to the minimum manipulation exerted on the cervix of these females, which don t cause injuries that could lead to exacerbated production of embryotoxic substances. Thus, when the transcervical AI technique is carried out through trained inseminators and without extreme manipulation of cervix, it becomes a good alternative for costs reduction in sheep AI, allowing the use of frozen semen in commercial applications. / A inseminação artificial (IA) com sêmen congelado em ovinos é limitada pelos altos custos da técnica por laparoscopia e pelos resultados variáveis obtidos com a IA transcervical. A IA por via transcervical requer pinçamento da cérvix, um procedimento que pode causar lesões localizadas, além de extensa manipulação uterina, podendo levar a uma síntese exagerada de prostaglandina pelo endométrio, alterando o ambiente uterino no momento da concepção. O objetivo deste estudo foi comparar a eficiência da IA transcervical, através da técnica de fixação e tracionamento da cérvix, em relação a IA por laparoscopia, bem como, determinar o efeito da aplicação de flunixin meglumine sobre a taxa de prenhez de ovelhas, inseminadas com sêmen congelado. Em ovelhas inseminadas em tempo-fixo, durante o período de anestro estacional, não houve diferença entre as técnicas transcervical e laparoscópica, quanto à taxa de prenhez (40%). Com relação ao uso de flunixin meglumine, o experimento foi realizado durante a estação reprodutiva da espécie ovina, efetuando-se a IA com observação de cio. Neste estudo não observou-se diferença quanto à taxa de prenhez entre ovelhas recebendo ou não flunixin meglumine (p>0,05), sendo de 68,9% no grupo controle e 60,0% no grupo em que foi aplicado flunixin meglumine uma hora antes da IA transcervical. Estes resultados se devem, provavelmente, à manipulação mínima exercida sobre a cérvix destas fêmeas, não causando lesões que pudessem levar à produção exacerbada de substâncias embriotóxicas. Assim, quando a técnica de IA transcervical é realizada por inseminadores treinados e sem manipulação excessiva da cérvix, esta se torna uma adequada alternativa de redução de custos na IA de ovinos, permitindo a utilização de sêmen congelado na ovinocultura.