Development and Analysis of a Feedback Treatment Strategy for Parturient Paresis of Cows

An intelligent on-line feedback treatment strategy based on nonlinear optimal control theory is presented for the parturient paresis of cows. A limitation in the development of an existing nonlinear mathematical model for the homogeneous system is addressed and further modified to incorporate a control input. A neural network based optimal feedback controller is synthesized for the treatment of the disease. Detailed studies are used to analyze the effectiveness of a feedback medication strategy and it is compared with the current impulse strategy. The results show that while the current practice may fail in some cases, especially if it is carried out before the condition of a patient deteriorates, the proposed continuous medication process may be initiated at any time. Moreover the proposed on-line continuous infusion strategy never leads to severe hypercalcemic problems, thereby avoiding an associated disastrous consequence of cardiac arrest. A comparison study with linear quadratic regulator theory brings out the advantages of the nonlinear control synthesis approach

Rumen-protected rice bran to induce the adaptation of calcium metabolism in dairy cows

Dairy cows suffer from hypocalcaemia in the days around calving, which may result in a condition generally known as milk fever. Calcium metabolism sharply shifts at the start of lactation, because Ca needs suddenly become much greater than at the end of gestation. Calcium metabolism is able to adapt to different physiological situations, but adaptation requires several days to be effective, resulting in this transient hypocalcaemia. A way to prevent milk fever is to induce adaptation of Ca metabolism weeks before calving by reducing dietary availability of Ca, to prepare Ca metabolism for calving. Rice bran contains a very low level of Ca and a high level of phytic acid, which is a well-know dietary antagonist of Ca in monogastric species. Preventing the ruminal degradation of phytic acid, rice bran can reduce the nutritional availability of dietary Ca in cows. In this thesis, fat coating and formaldehyde treatment proved effective to protect phytic acid in rice bran from ruminal degradation. Formaldehyde treatment was chosen as the preferred method, because it had no detrimental effects on voluntary feed intake. Feeding rumen-protected rice bran reduced dietary Ca availability, thereby inducing the adaptation of Ca metabolism. Furthermore, the product, fed before calving to multiparous cows, improved calcaemia for the first three days after calving. Rumen-protected rice bran, fed in the last weeks of gestation, could represent a practical dietary strategy to prevent milk fever

Influence of 25-hydroxyvitamin D and anionic salts on the calcium status of dairy cattle

Milk fever (parturient paresis / hypocalcaemia) is a metabolic disorder that usually occurs near parturition and at the onset of lactation in high producing multiparous dairy cows. Milk fever can indirectly contribute to an increased incidence of several diseases in early lactation. This study was conducted to compare two different feeding strategies to prevent milk fever, namely (i) the established concept of feeding a diet with a negative DCAD and (ii) a feeding strategy combining a negative DCAD supplement with 25-hydroxyvitamin D3 (25-OH-D3). Thirty dairy cows were used in a randomized block design and were selected and blocked by parity (second parity and later), 305 day mature equivalent milk production in the previous lactation and expected calving date. Within each of the 15 blocks, the cows were allocated to two experimental groups named DCAD and DCAD + HyD. Fifteen animals in the DCAD + HyD group received a daily oral dosage of 3 mg of 25-OH-D3. Plasma samples were collected from day 21 prepartum to 10 days postpartum and were analysed for 25-OH-D3, 1,25-dihydroxyvitamin D3, total and ionized calcium, phosphorus and magnesium. Samples were collected on day 21, 14, 10 prepartum and every second day to calving, 4 and 6 h postpartum and every second day up to day 10 after calving. Urinary samples for determination of macro minerals (calcium and phosphorus) were collected via manual stimulation on day 21, 14, 8 and 4 prepartum and day 4 postpartum. These samples were used to ensure that mild metabolic acidosis was achieved in both treatment groups. The metabolic acidosis was demonstrated by decreased urinary pH. Milk samples were collected on day 1, 4 and 10 postpartum and used for macro mineral (calcium and phosphorus) determination. This study did not achieve all of the expected results observed in similar experiments. No treatment differences could be detected for plasma Ca2+ concentrations (P>0.05) and the mean plasma Ca2+ concentrations were [1.086a mmol/L ± 0.010 (DCAD treatment) and 1.083a mmol/L ± 0.010 (DCAD + HyD treatment)] respectively.   Furthermore 1,25-(OH)2D3 plasma concentrations did not indicate any treatment differences (P>0.05). These results could be due to the fact that the experimental animals were not sufficiently challenged and therefore the combination of a low DCAD diet and Rovimix HyD did not influence the calcium homeostatic mechanisms as expected. A clear correlation between plasma 25-OH-D3 concentration and treatment duration was however demonstrated (P<0.001), indicating effective absorption of orally supplemented 25-OH-D3. Several authors demonstrated that feeding massive doses of vitamin D2 (30 million units) for extended periods led to clinical evidence of vitamin D toxicity. When 10 million IU of vitamin D3 were however administered intramuscularly within 10 days of parturition, a reasonable measure of protection against toxicity could be provided. It can be concluded from this study that longer feeding periods (± 21 days) than the proposed 10 days prior to calving can safely be implemented when feeding 3 mg 25-OH-D3 per animal per day (=240 mg Rovimix HyD 1,25%). CopyrightDissertation (MSc(Agric))--University of Pretoria, 2012.Animal and Wildlife Sciencesunrestricte

Vitamin D mediated Calcium and Phosphorus metabolism in cattle

Vitamin D metabolites and the major mammalian minerals phosphorus (P) and calcium (Ca) have a complex and detailed relationship. The relationship, especially for Ca, is delicately controlled by a range of hormones and is largely dependent on the animal's physiological state. Studies have identified that Vitamin D metabolites given in supraphysiological doses to cattle can manipulate Ca and P metabolism. Furthermore, large doses of the metabolite 25-hydroxy vitamin D (25-vitD) can replace the actions of active vitamin D, 1,25-dihydroxy vitamin D (1,25-vitD) and initiate increased absorption of both Ca and P from the digestive tract in mice. These findings led to the hypothesis that 25-vitD could be used to favorably manipulate the metabolism of both Ca and P in cattle. The studies undertaken within this thesis are focused on the use of 25-vitD in both the beef and dairy industries. A group of beef breed steers were recruited and trained to halter, stand in metabolism crates and spend extended periods of time in individual pens. For studies concerning Ca, urine was the most important measurement. An increase in urinary Ca excretion demonstrated that there has been an increase in available Ca, either from the diet or skeletal reserves. With P studies faecal P excretion and plasma P were important guides to changes in P metabolism. The results of the metabolism studies undertaken in the thesis identify that Ca and P homeostasis is manipulated by 25-vitD and the majority of the increase in availability of both Ca and P originates from the diet. This is further supported by the absence of bone degradation. Thus, the inclusion of 25-vitD in a typical anionic transition diet will increase Ca absorption prior to parturition, enabling labile bone Ca stores to remain intact and available for immediate use at parturition whilst increasing the amount of Ca available to the animal from both bone and diet. Furthermore, the combination of 25-vitD and anionic salts has physiological implications that allow sufficient generation of extracellular Ca at parturition. An increase in plasma 25-vitD concentrations, to approximately 375 ng/ml, facilitated an increase in the concentration of plasma P and a reduction in faecal P, which indicates that dietary P absorption was increased

Transition Nutrition for Improved Fertility, Productivity, and Health of Dairy Cattle

The transition period, from approximately three weeks before to three weeks after calving, is characterised by sudden and substantial changes in nutrient requirements as dairy cattle respond to the metabolic challenges of late pregnancy and early lactation. The success by which cows meet these challenges determines their productivity, health and reproductive success not only over transition, but also throughout the following lactation. Manipulations of the pre-calving and early lactation diet have led to persistent improvements in milk production, health and reproduction, leading us to pose the question, how can a relatively short intervention, applied during the per-partum or early lactation period have long lasting effects on fertility, health and productivity throughout lactation? This thesis compiles a collection of research that was undertaken to better understand the influence of nutritional intervention during the peri-parturient period on dairy cow fertility, health and production. Increased milk protein production and rapidly fermentable sugar intake were associated with a decreased proportion pregnant while increased fatty acid and starch intake, and metabolisable energy balance were associated with an increased proportion pregnant (Chapter 2). Inclusion of fats in the early lactation diet increased the pregnancy to service by 27% and tended to reduce calving to pregnancy interval (Chapter 3) and the magnitude of these responses to fat interventions varied among types of fat, possibly reflecting different roles, or provision of different fatty acids, from the different fat types. Feeding fats during transition may be an essential component of an integrated response to the challenges of controlling tissue mobilization in early lactation and limiting the amount of readily fermentable carbohydrate fed. Effects of dietary protein degradability and genetic merit on milk casein composition and yield were examined (Chapter 4) and variables including pre-calving metabolisable protein balance that predicted milk protein and casein yield and composition were identified. Increased pre-calving body weight and plasma alpha amino nitrogen and cholesterol concentrations were associated with increased milk, protein, and casein yields, but decreased milk protein and casein contents. Cows producing lower milk protein and casein content were less likely to become pregnant. Supplementary calcidiol and negative dietary cation-anion difference (DCAD) diets in the pre-partum period have beneficial effects on mineral and energy metabolism (Chapter 6 and 7), milk production (Chapter 7), and health and reproductive outcomes (Chapter 8). Supplementation with calcidiol improved composition and yield of colostrum and early lactation milk yield, when compared with cows supplemented with cholecalciferol (Chapter 7). Additionally, calcidiol supplementation decreased incidence of retained placenta and metritis while negative DCAD diets increased calcium concentration in the blood around calving and eliminated incidence of clinical milk fever in transition cows. The hypothesis that interactions between bone and energy metabolism observed in other species are present in dairy cattle and have feedback over time was also supported (Chapter 9), identifying relationships among concentrations of vitamin D metabolites, insulin-like growth factor 1, osteocalcin and glucose over time. Through the collection of research presented, this thesis is able to demonstrate that nutritional interventions applied during the peri-parturient period have homestatic, but also homeorhetic effects on metabolism, and can substantially influence reproductive, productive and health outcomes of dairy cows well into lactation. This work highlighted the complexity and interrelated nature of transition nutrition, and importantly showed that productivity does not have to come at the cost of fertility and health where diets are properly integrated. The insights gathered regarding fat, protein, energy, minerals and vitamin D interventions and the relationships of metabolites underlying these, gives us tools to move closer to identifying the components of optimal transition diets and understanding the mechanisms by which these relatively short term interventions can have powerful and long lasting effects of dairy cow fertility, productivity and health

Prophylaktische Wirkung zweimaliger oraler Calciumchlorid-Gaben gegen Gebärparese bei Kühen

6 Zusammenfassung Hailu Gebreselassie Prophylaktische Wirkung zweimaliger oraler Calciumchlorid-Gaben gegen Gebärparese bei Kühen Medizinische Tierklinik der Veterinärmedizinischen Fakultät, Universität Leipzig 99 Seiten, 57 Abbildungen, 12 Tabellen, 274 Literaturangaben, 5 Anhänge Die Gebärparese gehört zu den verlustreichen Stoffwechselstörungen bei Kühen. Deshalb hat ihre wirksame Prophylaxe eine wichtige Bedeutung. Als vorbeugende Maßnahme wird u.a. die orale Ca-Gabe um die Geburt praktiziert. Entgegen der üblichen viermaligen wird in dieser Arbeit eine zweimalige Applikation von CaCl2 (Calol® = CG- Gruppe) gegenüber einer unbehandelten Kontrollgruppe (KG) geprüft. Ziel der vorliegenden Untersuchungen war es deshalb, die Auswirkungen der zweimaligen CaCl2-Gaben auf Stoffwechselparameter festzustellen und den Prophylaxeeffekt gegen Gebärparese zu überprüfen. Zu diesem Zweck wurde 90 SB-Kühen zweimal das CaCl2-Präparat zur Zeit der Kalbung und 12 h (Stunden) post partum (p.p.) oral verabreicht. Die Menge des Präparates bei einer Verabreichung betrug 0,33 Liter und bestand aus 48,96 g CaCl2, 0,48 g Mg, 0,048 g Na, Pflanzenöl, Aroma- und Emulgatorvormischung. Dieser CG wurden 90 unbehandelte Kontrollkühe derselben Rasse gegenüber gestellt. Im Untersuchungszeitraum war bei 9 Kühen der KG und bei 5 Kühen der CG Gebärparese aufgetreten. Die Gebärparesehäufigkeit in der KG war signifikant höher als in der CG. Die Tiere der CG hatten 12 h nach der zweiten oralen Gabe von CaCl2 statistisch signifikant höhere Ca-, K- und Cl-Konzentrationen im Blut als die Kontrolltiere. Der Anstieg der Ca- und Pi- (anorganisches Phosphat) Konzentrationen war auch innerhalb der CG 1 Tag (d) p.p. statistisch gesichert. Die BHB-(ß-OH-Butyrat-)Konzentration der Kontrolltiere war bei der Kalbung und 1 d p.p. signifikant höher als die der Versuchstiere. Die Bilirubin- und Glucose- Konzentrationen sowie die CK- (Creatinkinase-)Aktivitäten ließen keine gesicherten Unterschiede zwischen den Entnahmen innerhalb der CG und KG erkennen. Innerhalb der beiden Gruppen waren die Pi-, BHB- und Harnstoffkonzentrationen 1 d p.p. signifikant höher, als bei der Kalbung. Im Gegensatz zu den Kühen der CG korrelierte das Ca bei den Tieren der KG 1 d p.p. gesichert negativ mit FFS (freie Fettsäure), Bilirubin, BHB und Mg. Die Zuordnung der untersuchten Parameter zu verschiedenen Klassen der FFSKonzentrationen (≤600; 600-1000 u. >1000 μmol/l) machte deutlich, dass in den wenigsten Fällen signifikante Differenzen errechnet werden konnten. Dies betraf die Parameter Ca, Glu97 cose, Mg, Na, K, Cl, Cholesterol und Protein. Lediglich für Pi ergaben sich in der KG und CG einen Tag nach der Kalbung signifikant niedrigere Konzentrationen. Erwartungsgemäß waren auch die Bilirubin-Konzentration in der KG und CG bei den höchsten FFS-Konzentrationen entsprechend gesteigert. Für die AST- (Aspartat Amino- Transferase) Aktivität traf dies auch für beide Gruppen zu, für die CK- Aktivität nur für die KG. Damit weisen diese Befunde darauf hin, dass bei gesteigerter Lipolyse nicht zwangsläufig niedrigere Ca-, aber niedrigere Pi- Konzentrationen zu erwarten sind. Diese Veränderungen folgen demzufolge unterschiedlichen Mechanismen. Ein etwas anderes Bild ergibt sich, wenn man die Ca- und Pi-Konzentrationen den höchsten BHB (>1,5 mmol/l) und Bilirubin-Konzentration zuordnet. In beiden Fällen sind einen Tag nach der Kalbung die Ca- und Pi-Konzentrationen signifikant vermindert. Das kann dadurch erklärt werden, dass die Steigerungen der BHB- und Bilirubin-Konzentrationen etwas längere Zeit beanspruchen als die Konzentrationssteigerung der FFS. Dadurch wird ein alimentärer Einfluss auf die Ca- und Pi-Konzentrationen im Blut möglich. Die festliegenden Kühe in der CG hatten am 1. d p.p. mit 2,19 mmol/l eine physiologische Ca-Konzentration. Sie war statistisch signifikant höher, als in der KG (1,49 mmol/l). Dagegen waren die festliegenden Kühe der beiden Gruppen bei der Kalbung hypophosphatämisch. Ihre Pi-Konzentrationen lagen zwischen 0,69-0,79 mmol/l. Die Cl- und Cholesterol- Konzentrationen sowie die CK- und AST-Aktivitäten der festliegenden Kühen der CG waren 1 d p.p signifikant höher als in der KG, die FFS- und Bilirubin-Konzentrationen der CG waren signifikant niedriger als in der KG. Somit führte die zweimalige reduzierte orale CaCl2- Gabe zur signifikanten Erhöhung der Ca-Konzentration in den Referenzbereich sowohl bei den nichtfestliegenden als auch festliegenden Kühen, d.h., dass die behandelten Kühe einen stabileren Ca-Stoffwechsel hatten. Mit der prophylaktischen Anwendung der halben praxisüblichen Dosierung des CaCl2-Präparats konnte eine ebenso gute Wirkung erzielt und die Gebärpareseinzidenz genauso gut reduziert werden, wie laut Literaturberichten mit der viermaligen Dosierung. Die Analyse der Festlieger in der CG machte deutlich, dass neben der Hypocalcämie weitere ätiologische Faktoren für die Gebärparese auch im Zeitraum bis drei Tage nach der Kalbung zu berücksichtigen sind. Dies wurde u.a. durch ein schlechteres Behandlungsergebnis der festliegenden Kühe in der CG deutlich. Der Energiestoffwechsel bzw. die Fettmobilisierung hatte dabei offensichtlich keine vordergründige Bedeutung und keinen besonderen Einfluss auf den Ca-Stoffwechsel

The effects of feeding a negative dietary cation-anion difference diet at two dietary calcium inclusion rates to close up dry cows on the subsequent lactation uterine health and fertility

Feeding a negative dietary cation-anion difference (DCAD) diet in the prepartum phase been associated with increased biological active blood Ca levels (ionized Calcium; iCa) in the first days postpartum, linked with decrease incidences of hypocalcemia (HC) and subclinical hypocalcemia (SCH), as well as a host of other periparturient disorders. This is achieved by altering the mineral composition of the prepartum diet to induce a slight metabolic acidosis environment to attenuating PTH sensitivity to circulating Ca levels. While this concept has been established in literature, the rate of inclusion of dietary Ca in a negative DCAD diet has not. The objective of this study was to determine at what concentration of dietary Ca to feed with a close-up dry cow negative DCAD diet and the effects on the subsequent uterine health, circulating inflammatory blood metabolites, ovulation dynamics, and fertility. Multiparous Holstein cows (n = 76) were enrolled at 50 days before expected calving date and followed until 75 days in milk (DIM). Treatments began at 28 days before expected calving and were: CON (n = 24), a positive DCAD diet with low dietary Ca (DCAD = 9.46 mEq/ 100 g DM; 0.4% DM); LOW (n = 26), a fully acidified DCAD diet (DCAD = -24.13 mEq/ 100 g DM; urine pH = 5.7) with low dietary Ca (0.4% DM); HIGH (n = 24), a fully acidified DCAD diet (DCAD = -23.97 mEq/ 100 g DM; urine pH = 5.7) with high dietary Ca (2.0% DM). Vaginal discharge was evaluated was at 4, 7, 10, 13, 15, 17, and 30 DIM via Metricheck (MC; 0-3 scale: 0 = clear mucus; 1 = mucus containing non-purulent material; 2 = mucus containing ≤ 50% purulent material; 3 = mucus containing > 50 % purulent material). Polymorponuclear (PMN) cell concentration in the uterus was evaluated at 15 and 30 DIM, and endometrial tissue samples were harvested at 30 DIM for glandular morphology and assessment of superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity as markers of oxidative stress. Blood plasma and serum samples were harvested at -28, -21, -14, -7, 15 and 30 DIM and were assessed for concentrations of lipopolysaccharide binding protein (LBP), serum amyloid A (SAA) and haptoglobin (HP). Ovarian dynamics was assessed at 7, 9, 11-17, 20, 30, 55, 62, and 69 DIM. Data collected were analyzed using PROC MIXED in SAS. Contrasts were CONT1 (CON vs the average of cows fed LOW and HIGH diets) and CONT2 (LOW vs HIGH). Cows fed CON tended to have a lower MC score (P = 0.06) than the average of cows fed LOW and cows fed HIGH. Cows fed LOW tended to have a higher MC score than cows fed HIGH. There were differences in uterine gland epithelial height where cows fed HIGH had greater epithelial height (P = 0.02) than cows fed LOW and cows fed CON tended to have shorter epithelial height (P = 0.06) than the average of cows fed LOW and cows fed HIGH. Cows fed HIGH also had a greater number of epithelial cells per gland (P = 0.05) than cows fed LOW. Anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) relive oxidative stress in cells. Cows fed HIGH had increased activity of SOD (P = 0.05) decreased activity of GPX (P < 0.001) than cows fed LOW calcium diet. Cows fed LOW had higher HP concentrations than cows fed HIGH in the prepartum (P = 0.01) and post-partum (P = 0.03) periods. Cows fed CON diet had higher (P = 0.01) HP concentration than the average of cows fed LOW and cows fed HIGH (contrast CON vs. LOW and HIGH) postpartum. Cows fed HIGH tended to have an increased likelihood of being pregnant at the first timed artificial insemination. Cows fed HIGH seemed to have an improved uterine environment due to alleviation of oxidative stress, an enhanced immune response to parturition and uterine discharge comparable to cows fed CON. In conclusion, the periparturient period is a challenging time to the dairy cow with numerous metabolic changes that affects lactation and reproductive performance. Calcium metabolism and homeostasis is an important factor and can be influenced by prepartum feeding management. Strategies such as feeding a negative DCAD diet to close-up dry cows has been credited with decreasing incidences of HC and SCH and improving reproductive performance. Additionally, feeding a negative DCAD diet with 2% dietary Ca inclusion seems to attenuate the reproductive health and fertility of the dairy cow

Effect of vitamin D3 on calcium homeostasis of beef steers

Supplementation of high levels of vitamin D3 (D3) to cattle has enhanced beef tenderness. However, high levels of D3 possess a food safety concern. Therefore, the objective of this thesis was to evaluate feeding strategies that would reduce the amount of D3 required to increase serum calcium (Ca) to levels where tenderness has been improved. In experiment 1, 15 steers (452 ±30kg) were fed with 75% barley grain-base concentrate and 25% barley silage (as fed) and 1.25,2.5 or 5 MIU D3/hd/d for 7 d. Feed intake was depressed (

The effect of prepartum synthetic zeolite A supplementation on the eating, lying, and activity behaviors of multiparous grazing dairy cows : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Animal Science at Massey University, Manawatū, New Zealand

Synthetic zeolite A is a precalving feed supplement that improves parturient blood calcium concentrations, thereby reducing hypocalcemia risk. Zeolite is associated with altered feeding behavior in housed cows and may affect lying and activity behaviors due to their established relationships with hypocalcemia. Furthermore, these responses may be affected by parity. This study determined the effect of feeding zeolite prepartum on eating, lying, and activity behaviors in multiparous grazing dairy cows during the transition period. Forty-three cows were randomly allocated to either a Zeolite treatment group (n = 21; individually fed 500 g/d zeolite in 2 kg DM/d maize silage for 18.2 ± 3.6 d prepartum) or a Control group (n = 22; fed maize silage only for 20.6 ± 4.1 d prepartum). Behavior data obtained from accelerometers were analyzed using repeated-measures ANOVA to determine the effects of treatment (Zeolite vs. Control), parity (Parity 2−3 vs. 4+), day, and their interactions, during 3 periods: PRE (-21 to -3 d), PERI (-2 to 2 d) and POST (3 to 28 d) relative to the day of calving (d 0). Parity 4+ cows spent a similar amount of time eating PRE (6.9 h/d) irrespective of treatment, whereas Parity 2–3 Zeolite cows varied in their eating time PRE (7.6 h/d), which was generally lower than that of Parity 2–3 Control cows (7.9 h/d). Zeolite cows also ate for 24 min/d less than Control cows PERI and lay down for 30 min/d longer POST. Regardless of treatment, Parity 2–3 cows ate for 0.6 – 5 min/h longer at night (1700 – 0559 h) and were more active than Parity 4+ cows, especially PRE. They also had shorter lying times PRE (30 min less/d; 1.6 – 4.7 min/h less at night) and PERI (48 min less/d), indicating younger cows ate more at night while their older herdmates were resting. These results suggest a subtle anorexic effect of zeolite in younger grazing dairy cows during precalving supplementation, whereas longer lying times may indicate improved cow comfort and welfare postcalving. Results also reflect possible competitive interactions and differences in time budgets between younger and older cows during the transition period

Optimal Neuro-Controller Synthesis for Impulse-Driven System

This paper presents a new controller design technique for systems driven with impulse inputs. Necessary conditions for optimal impulse control are derived. A neural network structure to solve the resulting equations is presented. The solution concepts are illustrated with a few example problems that exhibit increasing levels of difficulty. Two linear problems-one scalar and one vector-and a benchmark nonlinear problem-Van Der Pol oscillator-are used as case studies. Numerical results show the efficacy of the new solution process for impulse driven systems. Since the theoretical development and the design technique are free from restrictive assumptions, this technique is applicable to many problems in engineering and science