Thesis (Ph. D.)--Oregon State University, 2006. / Printout. Includes bibliographical references (leaves 110-121). Also available on the World Wide Web.

O presente trabalho objetivou validar o modelo experimental de indução de hipocalcemia, por meio de solução de EDTA, utilizado em bovinos para a espécie eqüina, bem como estudar o quadro sintomatológico, algumas variáveis bioquímicas e a resposta ao tratamento com cálcio. Foram utilizados 24 animais, 12 novilhas e 12 éguas, aleatoriamente distribuídos em 5 animais nos grupos controles e 7 animais nos grupos tratados em cada espécie. Foi injetado continuamente através de cateter intravenoso, uma solução de ácido etilenodiaminotetracético dissódico (EDTA) a 5% com pH ajustado para 7,4, e com velocidade controlada de 220 mL/hora, até que o animal apresenta-se os sinais clínicos clássicos de hipocalcemia como decúbito esternal com posição de auto-auscultação ou decúbito lateral. O grupo tratado com cálcio foi imediatamente medicado com uma solução contendo 2,44 g de cálcio, 0,47 g de fósforo, 0,185 g de magnésio e 5 g de glicose para cada 100 mL, na dose de 1mL/kg/PV, no decorrer de 30 minutos. O grupo controle foi infundido com uma solução fisiológica de cloreto de sódio na mesma velocidade utilizada para a solução de cálcio. Após este período os animais do grupo controle foram tratados com o mesmo produto e protocolo supracitado para recuperação dos animais. Um minucioso exame físico, bem como coleta de amostras sangüíneas foram realizados nos tempos T0 (antes do início da infusão de EDTA), T1 (Fase I caracterizada por tremores musculares), T2 (ao final da infusão com EDTA), T3 (Após o término do tratamento) e T4 (24 horas após o término do experimento). Todas as novilhas mostraram diminuição temporária da concentração de cálcio total e livre, fósforo sérico, e apresentaram quadro clássico de hipocalcemia. A taquicardia e a hipofonese desapareceram no decorrer do tratamento, sendo também observado aumento significativo no cálcio livre e total, e fósforo sérico. Nos eqüinos, o modelo produziu queda nos valores séricos de cálcio total e livre, e de magnésio, além de quadro clássico de hipocalcemia, semelhante a casos clínicos relatados e ao quadro experimental em bovinos. Taquicardia, hipofonese, atonia cecal e meteorismo decorrente da hipocalcemia foi gradativamente desaparecendo com o tratamento, voltando a freqüência cardíaca a valores basais após o tratamento. O modelo experimental de indução de hipocalcemia usado classicamente em bovinos foi bastante eficiente para desenvolver um quadro clínico característico desta enfermidade em eqüinos, sendo este facilmente corrigido em ambas espécies com o uso da solução utilizada no tratamento. / The present study aims to validate in equine the induction model of hypocalcemia used in bovine by EDTA infusion and study the clinical picture, biochemical profile and treatment response in booth species. Were utilized 24 animals, 12 heifers and 12 mares randomly distributed in seven animals on treated group and five animals on control group in each species. The induction model was carried on by continuous EDTA infusion into jugular vein, with control speed of 220 mL/hour, until the animals present clinical sings of hypocalcemia such as lateral decumbency and selfauscultation attitude. After that, the treated group received a calcium (Ca) solution (2.44 g/ 100 mL) enriched with phosphorus (P) (0.47 g/ 100 mL), magnesium (Mg) (0.185 g/ 100 mL) and glucose (5 g/ 100 mL) with a dose of 1 mL/kg of body weight in 30 minutes, in while, the control group was treated with the same dose of saline solution (0.9 %). Clinical examination and blood withdraws were performed in times T0 (basal time), T1 (beginning of hypocalcemia); T2 (end of EDTA infusion); T3 (end of treatment) and T4 (24 hours after the induction). All the heifers show temporary blood calcium and phosphorus reduction and present classical clinical picture of hypocalcemia. The treated group present fully clinical recovery and blood calcium and P increasing. In mares the induction model provokes fall of Ca and Mg and the animal presented a classical picture of hypocalcemia closely to the presented by the heifers. Most evident sing were increasing heart beat, hypophonesis, cecal atony, muscular contractions and crescent inquietation; followed by decumbency and apathy. Those symptoms were reversed after calcium treatment. For some of the variables study, significative difference between the groups in T3 was found in bovine (ruminal movements; time for capillary fulfilling - TCF; blood Ca) and equine (cecal movements; blood Ca and Mg). The experimental model classically used on bovines performed excellent in mares, with animal safety and efficacy on provokes hypocalcemia clinical sings. The syndrome was easily corrected, in both species, by calcium solution.

O hiperparatireoidismo (HPT) secundário é uma complicação da doença renal crônica. A paratireoidectomia total com autoimplante proporciona bons resultados no seu tratamento, mas alguns doentes não desenvolvem níveis adequados de hormônio da paratireóide (PTH) após a operação. Os objetivos, do presente estudo, foram analisar fatores que poderiam interferir no funcionamento do autoimplante de glândula paratireóide e quantificar a taxa de hipofunção segundo alguns critérios. Casuística e Métodos: em um estudo prospectivo e observacional, foram analisados a idade, sexo, peso, altura e a etnia. A causa da doença renal crônica (DRC), tempo de DRC antes da paratireoidectomia, tempo de diálise, antecedente de intoxicação por alumínio e tempo de diagnóstico do HPT. Os dados bioquímicos estudados foram os níveis pré-operatórios de fósforo, cálcio total, cálcio iônico, PTH e fosfatase alcalina e aos 6 meses e 1 ano de pós-operatório. Registrada a quantidade de cálcio (gluconato e carbonato) e calcitriol ofertada no pós-operatório sendo realizada durante a primeira semana, no primeiro, terceiro sexto mês de pós-operatório. A histologia da glândula implantada foi analisada. Os pacientes foram divididos, segundo os níveis preconizados de PTH para indivíduos normais e segundo as recomendações da Fundação Nacional do Rim dos Estados Unidos da América (K/DOQI), em grupos hipofuncionante (grupo 1) e funcionante ( grupo 2). Resultados: Entre julho de 2007 e dezembro de 2008, 48 pacientes (18 homens e 30 mulheres) foram submetidos à paratireoidectomia total com autoimplante imediato. A média de idade dos indivíduos foi 44,7 anos (EP: 12,6), a do tempo de diálise foi 9,6 anos (EP: 5,1), a média do tempo de diagnóstico do hiperparatireoidismo de 2,6 anos (EP: 2). A principal causa da doença renal crônica foi a hipertensão arterial em 16 indivíduos (33,3%) seguida de causa indefinida em 12 (25%), GESF em 5 (10,4%), diabetes mellitus em 4 (8,3%). Com relação ao número de fragmentos implantados, houve tendência a uma diferença entre os grupos 1 e 2 (p= 0,14). Houve tendência a uma diferença entre os grupos 1 e 2 (p= 0,1) no que diz respeito a histologia da glândula implantada. O índice de hipofunção do auto implante, em 1 ano, foi de 21,27% no critério do nível de PTH para indivíduos normais e de 72,9% segundo as recomendações do KDOIQ. As complicações e óbitos por causa cardiovascular não diferiram entre os grupos. CONCLUSÃO: a frequência de hipofunção do implante imediato de paratireóide foi de 21,27% e de 72,9% segundo as recomendações do KDOQ e não houve a identificação de fatores preditivos para sua hipofunção. / The secondary hyperparathyroidism (HPT) is a complication of chronic kidney disease. A total parathyroidectomy with autograft provides good results in treatment, but some patients do not develop adequate levels of parathyroid hormone (PTH) after operation. The objectives of study were to analyze factors that could interfere with the function of the parathyroid gland autograft and measure the rate of hypofunction according several criteria. Patients and Methods: a prospective observational study were analyzed age, sex, weight, height and ethnicity. The cause of chronic kidney disease (CKD), duration of CKD prior to parathyroidectomy, duration of dialysis, previous aluminum intoxication and time of diagnosis of HPT. The biochemical data studied : preoperative levels of phosphorus, total calcium, ionized calcium, PTH and alkaline phosphatase and 6 months and 1 year postoperatively. Recorded the amount of calcium (gluconate and carbonate) and calcitriol offered postoperative being held during the first week, the first, third, sixth month postoperatively. Histology of the implanted gland was analyzed. Patients were divided according to the recommended levels of PTH for normal individuals and in accordance with the recommendations of the National Foundation Kidney the United States of America (K / DOQI) in hypofunction groups (group 1) and functional (group 2). Results: Between July 2007 and December 2008, 48 patients (18 men and 30 women) underwent total parathyroidectomy with immediate autograft. The mean age was 44.7 years (SE: 12.6), the duration of dialysis was 9.6 years (SE: 5.1), the average time of diagnosis of hyperparathyroidism 2.6 years (EP: 2). The main cause of chronic renal disease was hypertension in 16 patients (33.3%) followed by unknown cause in 12 (25%), FSGS in 5 (10.4%), diabetes mellitus in 4 (8.3%.). The number of implanted fragments, there was a trend to a difference between groups 1 and 2 (p = 0.14). There was a trend to a difference between groups 1 and 2 (p = 0.1) as regards the histology of the gland implanted. The rate of self hypofunction implant at 1 year was 21.27% at the discretion of the PTH level in normal individuals and 72.9% according to the recommendations of KDOIQ. Complications and deaths from cardiovascular causes did not differ between groups. CONCLUSION: The rate of hypofunction of the parathyroid immediate implant was 21.27% and 72.9% according to the recommendations of KDOIQ and there was no identification of predictive factors for its hypofunction.

The incidence of hypocalcemia and bone mineral density (BMD) changes in end-stage renal disease (ESRD) patients on denosumab remains unclear. We performed this meta-analysis to assess the incidence of denosumab-associated hypocalcemia and effects of denosumab on BMD in ESRD patients. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through November 2017 to identify studies evaluating incidence of denosumab-associated hypocalcemia and changes in serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and BMD from baseline to post-treatment course of denosumab in ESRD patients. Study results were pooled and analyzed using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017081074). Six observational studies with a total of 84 ESRD patients were enrolled. The pooled estimated incidence of hypocalcemia during denosumab treatment was 42% (95% CI 29–55%, I2 = 0%). Hypocalcemia occurred approximately 7 to 20 days after the first dose and reached nadir of low calcium levels in the first 2 weeks up to 2 months. However, there were no significant changes in serum calcium or phosphate from baseline to post-treatment course (≥ 3 months after treatment) with mean differences [MDs] of 0.20 mg/dL (95% CI, − 0.30 to 0.69 mg/dL) and − 0.10 mg/dL (95% CI, − 0.70 to 0.49 mg/dL). There were significant reductions in ALP and PTH levels with standardized mean differences (SMDs) of − 0.65 (95% CI − 1.13 to − 0.16) and − 1.89 (95% CI − 3.44 to − 0.34), respectively. There were significant increases in T-scores with MDs of 0.39 (95% CI 0.10 to 0.69) and 0.79 (95% CI 0.60 to 0.98) for lumbar spine and femoral neck, respectively. Our study demonstrates the estimated incidence of denosumab-associated hypocalcemia in dialysis patients of 42%. From baseline to post-treatment course, although there are no differences in serum calcium and phosphate, our findings suggest significant reductions in ALP and PTH and a significant increase in BMD. Currently, denosumab should not be considered as the treatment of choice in ESRD patients until more safety and efficacy data are available.

No description available.

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-09T13:37:10Z No. of bitstreams: 1 Jobson Filipe de Paula Cajueiro.pdf: 767324 bytes, checksum: 776ab3e5c28585de71b32d4d723d5483 (MD5) / Made available in DSpace on 2017-02-09T13:37:10Z (GMT). No. of bitstreams: 1 Jobson Filipe de Paula Cajueiro.pdf: 767324 bytes, checksum: 776ab3e5c28585de71b32d4d723d5483 (MD5) Previous issue date: 2014-02-07 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Hypocalcemia in dairy cows has been studied around the world, mainly due to its impact on animal production and productivity, will be related to various diseases. However, few studies have been conducted on this disease in small ruminants, especially in dairy goats. Therefore , the aim of this study was to determine the concentrations of calcium during the transition period in dairy goats in order to differentiate groups of hypocalcemic animals (G1) and normal calcium (G2), in order to infer the influence of subclinical hypocalcemia in profile metabolic thereof. For this, 35 goats, otherwise healthy, pregnant, primiparous and multiparous, crossbred or purebred dairy breeds used. Blood samples were collected by jugular venipuncture before delivery [30 , 20 and 10 days before parturition (dap)] , on the day of partum and post -partum [10,20,30,40,50 and 60 days later parturition (dpp)]. The variables measured were: glucose, non-esterified fatty acids (NEFA), β - hydroxybutyrate (BHB), cholesterol, triglycerides, amylase, total protein (TP), albumin, urea, creatinine, aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), creatine kinase (CK), total calcium, phosphorus (P), magnesium (Mg), chlorides, hormones cortisol and insulin, as well as ions Ca++, Na+ and K+. Were considered to have subclinical hypocalcemia goats showed that Ca++≤ 0.72mmol/L. The statistical model used for analysis was ANOVA . In G1 concentrations of Ca++ remained below that of G2 and the biggest difference ( P < 0.001 ) occurred at parturition . The highest concentrations of NEFA were observed at birth in both groups, but were higher in G1 (P< 0.03) than the G2 at delivery and during the pre -partum. The BHB had a slight growth from beginning to 40dpp in both the G1 and G2 and there were no differences between them. The behavior of amylase was increased in antepartum reaching their highest values to 10dpp and remained stable postpartum in both groups, did not return to their initial values. A decrease in the values of triglycerides 20dap until 10dpp and differences (P<0.05) were found between the pre-and postpartum in both groups occurred. Cholesterol remained slight growth in postpartum, a little more evident in G2 than in G1, however these did not differ. Reduction in the concentration of insulin to 10dap in both groups, but in this G1 was greater (P˂0.001) that some times postpartum. The highest values of cortisol and glucose occurred at delivery and there were no differences between groups. The PT values were rising delivery to 30dpp not returning to baseline values in both G1 and G2. Albumin fell to 20dap and grew from birth up to 30dpp when returned to its initial value in both groups. The lower (P<0.05) values of total calcium is given at birth and the G1 was lower than G2 in almost the entire period. It is concluded that in subclinically goats hypocalcemic serum concentrations of Ca++ fall before the normocalcêmicas goats and remain lower throughout the transition period and that some variables of the metabolic profile as NEFA, glucose, insulin and total calcium are strongly influenced by the Ca++. Furthermore, the lower food intake by goats with subclinical hypocalcemia is one of the main factors affecting the metabolic profile and probably the productivity of these animals. However, other studies should be conducted to measure the effects of this disease in its subclinical form , the production rates and the emergence of other diseases in the transition period in dairy goats. / A hipocalcemia em vacas leiteiras tem sido objeto de estudos ao redor do mundo, principalmente em função de seu impacto na produção e produtividade animal, por estar relacionada á diversas enfermidades. Entretanto, poucos trabalhos sobre esta enfermidade foram realizados em pequenos ruminantes, sobretudo em cabras leiteiras. Portanto, o objetivo deste trabalho foi determinar as concentrações de cálcio durante o período de transição em cabras leiteiras, afim de, diferenciar grupos de animais hipocalcêmicos (G1) e normocalcêmicos (G2), com o objetivo de inferir a influência da hipocalcemia subclínica no perfil metabólico destes. Para tanto, 35 cabras, hígidas, gestantes, primíparas e multíparas, mestiças ou puras de raças leiteiras foram utilizadas. Amostras de sangue foram colhidas por venopunção jugular no pré-parto [30, 20 e 10 dias antes do parto (dap)], no dia do parto e no pós-parto [10, 20, 30, 40, 50 e 60 dias depois do parto (dpp)]. As variáveis mensuradas foram: glicose, ácidos graxos não esterificados (AGNE), β-hidroxibutirato (BHB), colesterol, triglicerídeos, amilase, proteínas totais (PT), albumina, uréia, creatinina, aspartato aminotransferase (AST), gama glutamiltransferase (GGT), creatina quinase (CK), cálcio total, fósforo (P), magnésio (Mg), cloretos, os hormônios cortisol e insulina, bem como os íons Ca++, Na+ e K+. Foram considerados com hipocalcemia subclínica as cabras que apresentaram Ca++≤0,72mmol/L. O modelo estatístico empregado para análise dos resultados foi a ANOVA. No G1 as concentrações de Ca++ mantiveram-se sempre abaixo do G2 e a maior diferença (P<0,001) ocorreu no dia do parto. As maiores concentrações de AGNE foram verificadas no parto, em ambos os grupos, porém no G1 foram maiores (P<0,03) que no G2 no parto e durante o pré-parto. O BHB teve um discreto crescimento do início até o 40dpp, tanto no G1 quanto no G2 e não houve diferenças entre eles. O comportamento da amilase foi crescente no pré-parto alcançando seus maiores valores aos 10dpp e manteve-se estável no pós-parto, em ambos os grupos, não retornando aos seus valores iniciais. Ocorreu uma queda nos valores dos triglicerídeos dos 20dap até os 10dpp e diferenças (P<0,05) foram verificadas entre o pré e o pós-parto, em ambos os grupos. O colesterol manteve discreto crescimento no pós parto, um pouco mais evidente no G2 que no G1, entretanto estes não diferiram. Houve redução na concentração da insulina aos 10dap em ambos os grupos, porém no G1 esta foi mais expressiva (P˂0,001) que alguns momentos do pós-parto. Os maiores valores do cortisol e da glicose ocorreram no parto e não ocorreram diferenças entre os grupos. Os valores de PT foram crescentes do parto aos 30dpp não retornando aos valores iniciais tanto no G1 quanto no G2. A albumina caiu aos 20dap e apresentou crescimento a partir do parto até aos 30dpp quando retornou ao seu valor inicial em ambos os grupos. Os menores (P<0,05) valores do cálcio total se deram no parto e o G1 foi menor que o G2 em quase todo o período. Conclui-se então que em cabras subclinicamente hipocalcêmicas as concentrações séricas do Ca++ caem antes que nas cabras normocalcêmicas e permanecem mais baixas durante todo o período de transição e que algumas variáveis do perfil metabólico como AGNE, glicose, insulina e o cálcio total sofrem forte influência do Ca++. Além disso, a menor ingestão alimentos pelas cabras com hipocalcemia subclínica é um dos principais fatores de interferência no perfil metabólico e provavelmente na produtividade destes animais. Contudo, outros trabalhos devem ser realizados a fim de mensurar os efeitos desta doença, na sua forma subclínica, nos índices produtivos e no surgimento de outras enfermidades no período de transição em cabras leiteiras.

Die hypocalcämische Gebärparese, insbesondere die subklinische Hypocalcämie, die oft nicht erkannt wird und Ursache vieler sekundär auftretender Folgeerkrankungen ist, stellt in der intensiven Milchviehhaltung ein bedeutendes Problem dar. Inzwischen gibt es eine Reihe verschiedener Vorbeugungsstrategien, wobei der Einsatz von Zeolith A als Ca-Binder in der Ration gegen Ende der Trächtigkeit eine relativ neue Präventionsmöglichkeit darstellt. Da zu diesem Futterzusatzstoff noch wenige Untersuchungen, insbesondere auf Nebeneffekte vorliegen, war das Ziel dieser Studien, den Einfluss von Zeolith A in verschiedenen Dosierungen auf die Futteraufnahme, den Energiestoffwechsel, die Futterverdaulichkeit und den Ca-, Mg- und P-Stoffwechsel sowie in hohen Dosierungen auch auf den Spurenelement-stoffwechsel zu untersuchen. Des Weiteren sollte untersucht werden, wie sich Zeolith A im Verdauungstrakt hinsichtlich der Freisetzung von Al verhält. In einer ersten Studie an 46 Kühen (≥ 3. Laktation), die in zwei Gruppen unterteilt wurden, wurde Zeolith A in einer Dosierung von 90 g/kg Trockensubstanz (T) in den letzten 2 Wochen der Trächtigkeit bis zum Kalbetag in eine totale Mischration (TMR), welche zur freien Aufnahme vorgelegt wurde, eingemischt. Die Zeolith A-Zulage ante partum zeigte peripartal eine stabilisierende Wirkung auf die Ca-Konzentration im Serum (> 2 mmol/l). Der Rückgang der Häufigkeit der Hypocalcämie (< 2 mmol/l) am Tag der Kalbung lag bei 76 %. Die mittlere Mg-Konzentration im Serum war bei den Kontrolltieren am Tag der Kalbung und 1 Tag post partum signifikant höher im Vergleich zu den Tieren der Versuchsgruppe, lag aber in beiden Gruppen im physiologischen Bereich (0,75-1,30 mmol/l). Auf die Spurenelement-konzentrationen (Cu, Zn, Mn und Fe) im Plasma wurde kein Zeolith A-Effekt festgestellt. Allerdings zeigten die Zeolith A-supplementierten Kühe ante partum einen signifikanten Rückgang in der Futteraufnahme, welche in einer negativen Energiebilanz mit einem signifi-kanten Anstieg der freien Fettsäuren und des Beta-Hydroxybutyrats im Serum resultierte. Dieser Effekt hatte allerdings keine Auswirkung auf die Futteraufnahme post partum und auf die Milchleistung in den ersten 105 Tagen der Folgelaktation. Des weiteren war die mittlere Konzentration des anorganischen Phosphats (Pi) bereits 7 Tage nach Beginn der Zeolith A-Zulage signifikant niedriger im Vergleich zu den Tieren der Kontrollgruppe und lag bis zum Tag der Kalbung deutlich unter der unteren physiologischen Grenze von 1,25 mmol/l. Die zweite Studie war ein Dosis-Wirkungsversuch an 80 Milchkühen (1.-7. Laktation) mit verschiedenen Zeolith A-Dosierungen (0, 12, 23 bzw. 43 g Zeolith A/kg T TMR). Dazu wurden die Tiere ca. 4 Wochen ante partum in 4 Gruppen und für die Untersuchung des Mineralstoffwechsel noch in zwei Untergruppen (1. + 2. Laktation bzw. ≥ 3. Laktation) unterteilt. Die Tiere erhielten eine TMR ad libitum vorgelegt. In den letzten zwei Wochen erhielten die Tiere Zeolith A in die Ration eingemischt. Eine Einmischung von 43 g Zeolith A/kg T TMR zeigte auf den Ca-, Mg- und Pi-Stoffwechsel sowie auf die Futteraufnahme und den Energiestoffwechsel vergleichbare Effekte wie in der ersten Studie bei einer Zulage von 90 g/kg T TMR. Eine Zeolith A-Zulage von 23 g/kg T TMR bei einem Zeolith A/Ca-Verhältnis von 5,6:1 hatte ebenfalls noch einen stabilisierenden Effekt auf den peripartalen Ca-Stoffwechsel (> 2 mmol/l) bei Kühen ≥ 3. Laktation, jedoch ohne markanten Rückgang in der Futteraufnahme. In dieser Tiergruppe war ein Rückgang der Häufigkeit der Hypocalcämie um 71 % zu verzeichnen. Diese Tiere zeigten auch nur eine moderate Hypophosphatämie. Eine Zeolith A-Zulage von 12 g/kg T TMR zeigte dagegen keine Effekte. In einem Stoffwechselversuch an 8 doppelt fistulierten Milchkühen (Pansen und proximales Duodenum) wurde schließlich der Einfluss von Zeolith A auf verdauungsphysiologische Para-meter und den Mineralstoffwechsel, insbesondere des Phosphors im Verdauungstrakt, sowie auf die Freisetzung von Al aus dem Zeolithverband untersucht. Die Tiere erhielten Mais- und Grassilage und Kraftfutter. Es wurde 0, 10 bzw. 20 g Zeolith A/kg T über einen Zeitraum von 3 Wochen mit dem Kraftfutter verabreicht. Eine Zeolith A-Zulage führte zu einer signifikant reduzierten scheinbaren ruminalen Verdaulichkeit der T sowie der ruminal fermentierten organischen Substanz. Allerdings waren in der fäkalen Ausscheidung der Nährstoffe keine signifikanten Unterschiede zwischen den Fütterungsgruppen festzustellen. Es zeigte sich kein Effekt auf die Ca- und Mg-Verdauung. Dagegen korrelierte die Konzentration des löslichen P im Pansen signifikant negativ mit der mittleren Zeolith A-Aufnahme. Des Weiteren hatten die Kühe mit einer Zeolith A-Zulage von 20 g/kg T eine signifikant höhere fäkale Ausscheidung des Gesamtphosphors im Vergleich zu den Tieren der Kontrollgruppe. Die herabgesetzte Bio-verfügbarkeit von P resultierte in einer signifikant erniedrigten Pi-Konzentration im Serum. Gleichzeitig war eine signifikant erhöhte Konzentration des gelösten Al im Pansen und ein signifikant höherer Fluss des gelösten Al im Duodenum festgestellt worden was auf eine Instabilität des Zeolithverbands beruht. Da eine Zeolith A-Dosierung von 12 g/kg T keinen Effekt auf den Ca-Stoffwechsel und eine Dosierung 43 g/kg T unerwünschte Effekte zeigte kann anhand dieser Untersuchungen geschlussfolgert werden, dass eine Einmischung in einem Bereich von 20 bis 30 g Zeolith A/kg T TMR, was bei einer mittleren täglichen T-Aufnahme von 10 kg ca. 200 bis 300 g Zeolith A/Tier/Tag entspricht, bei einem Zeolith A/Ca-Verhältnis von 6 bis 10:1 in der Ration in den letzten 2 Wochen der Trächtigkeit zur Vorbeugung der peripartalen Hypocalcämie zu empfehlen ist, ohne dass negative Effekte auf die Tiergesundheit zu erwarten sind. / Parturient paresis is known to be a frequent problem in high-yielding dairy cows. Subclinical hypocalcemia around calving is especially of particular importance, because it often remains undetected and may cause secondary diseases. In practice different preventive methods have been established, whereas feeding of zeolite A (synthetic sodium-aluminium-silikate) as a calcium binder in the last two weeks of pregnancy is a new strategy to prevent parturient hypocalcemia. However, there exists only little information about side effects of zeolite addition. The aim of this study was to investigate the influence of zeolite A, in several doses, on feed intake, energy metabolism, nutrient digestibility, as well as on calcium (Ca), magnesium (Mg) and phosphorus (P) metabolism, and in high doses on trace element metabolism. Further, it was to investigate the mechanism of zeolite A in the gastrointestinal tract, focused on releasing aluminium (Al). In a first study with 46 cows (≥ 3rd lactation) zeolite A was tested in a dose of 90 g/kg dry matter (DM) in the last two weeks of pregnancy. Therefore the cows were divided in two groups (control and zeolite supplemented group). All cows were fed a total mixed ration (TMR) ad libitum. The supplementation of zeolite A had a stabilising effect on Ca concentration in serum (> 2 mmol/l) around calving. The reduction of the hypocalcemia incidence (< 2 mmol/l) was 76 % on the day of calving. The Mg-concentration in serum was significantly higher for the cows without zeolite A supplementation compared to the cows of the experimental group on the day of calving and on the day after calving. However, the mean serum Mg concentration stayed in the physiological range (0.75-1.30 mmol/l) for both groups. No significant effect of the zeolite A supplementation was observed on the mean plasma concentration of trace elements (copper, zinc, manganese, iron). However, the zeolite A supplementation led to a significantly reduced feed intake ante partum, which resulted in a negative energy balance. Furthermore, non esterified fatty acid and beta-hydroxybutyrate in serum were increased significantly. However, no significant differences were observed in feed intake post partum as well as in milk yield in the first 105 days in the subsequent lactation between the two groups. Furthermore, zeolite A supplementation decreased significantly the concentration of inorganic phosphate (Pi) in serum. Seven days after beginning zeolite A supplementation, on the day of calving, the mean Pi-concentration was considerably below the physiological limit of 1.25 mmol/l. In the second study, zeolite A was tested in several lower doses. Therefore 80 dairy cows (1st – 7th lactation) were divided into four groups in the last 4 weeks of pregnancy. Additionally, the cows of each group were divided in two subgroups (1st + 2nd lactation and ≥ 3rd lactation) to determine the influence of zeolite A on mineral metabolism. All animals were fed a TMR ad libitum. In the last two weeks the cows received a daily dose of 0, 12, 23 and 43 g zeolite A/kg DM. Zeolite A supplementation of 43 g/kg DM showed comparable effects on Ca, Mg, and Pi metabolism, as well as on feed intake and energy metabolism as in the first study. For older cows (> 3rd lactation), supplementation of 23 g zeolite A/kg DM, and a zeolite A-Ca ratio of 5.6:1 resulted also in a stabilising effect on Ca metabolism (> 2 mmol/l) around calving without significant reduction of feed intake. The incidence of hypocalcemia was reduced by 71 %. The cows showed only a moderate hypophosphatemia. A zeolite A supplementation of 12 g did not have any preventive effects. In a metabolic-study with eight double fistulated dairy cows (rumen and proximal duodenum), the influence of zeolite A supplementation on several physiological parameters of digestion and on mineral metabolism, especially P in the rumino-intestinal-tract, was determined. Further releasing of Al from the zeolite structure was investigated. The cows were fed a maize/grass-silage (60:40 % based on DM) and concentrate. Several doses of zeolite A (0, 10 and 20 g/kg DM) were added to the concentrate over a period of three weeks. Zeolite A supplementation resulted in a significantly reduced ruminal digestibility of dry matter (DM) and fermentation of organic matter. No effect was observed on faecal digestion of DM and OM. Digestion of Ca and Mg in the rumino-intestinal tract was not influenced by zeolite A supplementation. However, the concentration of soluble P in rumen fluid correlated negatively with the mean zeolite A intake. The faecal excretion of total P increased significantly for cows with a zeolite A dose of 20 g/kg DM compared to the control group. The reduced bioavailability of P resulted in a significantly decreased concentration of Pi in serum. The zeolite A supplemented cows further showed a significantly higher concentration of soluble Al in rumen fluid as well as a significantly higher flow of soluble Al at the duodenum, which is a consequence of an instability of the zeolite structure. According to these results it can be concluded that a daily amount of 20 to 30 g zeolite A/kg DM, which complies a daily amount of 200 to 300 g zeolite A/cow at a daily DM intake of 10 kg, with a zeolite-Ca ratio of 6–10 to 1, for two weeks ante partum seems to be an adequate dose for reducing subclinical hypocalcemia in older cows without negative side effects on animal health. At an expected daily mean DM intake of 10 kg it is a daily amount of 200 to 300 g zeolite A/cow. A zeolite dose of 12 g/kg DM did not have any effect on Ca metabolism, and a dose of 43g/kg DM showed negative side effects.

Submitted by Rosangela Silva (rosangela.silva3@unioeste.br) on 2018-05-28T15:05:21Z No. of bitstreams: 2 Luís Henrique Cerqueira Vila Verde.pdf: 1205701 bytes, checksum: 917c89ccf0c450e4e8d17634346f026b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-05-28T15:05:21Z (GMT). No. of bitstreams: 2 Luís Henrique Cerqueira Vila Verde.pdf: 1205701 bytes, checksum: 917c89ccf0c450e4e8d17634346f026b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-03-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Vitamin D (VD) plays an important role in the development and maintenance of bone tissue. At normal levels, it has positive effect on volume, bone quality as well as its density. Considering the large number of people who present serum changes of the same, this research aims to observe the rate of hypovitaminosis D (hD) in the study population and the factors that may influence the incidence of hD, and to evaluate the influence of hD on peri-implant clinical and radiographic conditions. All the participants of the groups were submitted to a Semi-quantitative Food Frequency Questionnaire on the intake of dietary calcium (QFASQ), in order to evaluate the risk factors. Patients were submitted to laboratory tests of 25-hydroxyvitamin D dosing, those with a serum LDL level of less than 30ng / mL were allocated to the abnormal (insufficient or defficient) group and the participants with dosages equal to or greater than 30ng/mL were allocated to the normal (sufficient) group. Participants received the following evaluations: peri-implant clinical analysis (depth of probing, keratinized mucosa width, modified groove bleed index, modified plaque index), radiographic analysis (distance between the implant cervical and the mesial and distal). Patients who were allocated to the abnormal group were submitted to VD replacement, and a new clinical and radiographic analysis was performed. It was found that in the initial study population about 36% of individuals had hD. As for the food questionnaire, lower intake of milk products, such as yogurt and lower frequency of physical activities, showed a higher risk for one hD. Clinical analysis showed that VD was statistically non-statistically significant for probing depth, keratinized mucosal width, modified plaque index, and for modified bleeding index between the 2 periods, in relation to peri-implant parameters. It was concluded that less than half of the sample had hD and calcium-rich foods may contribute to normal serum levels of VD. VD did not influence the peri-implant clinical parameters studied. / A vitamina D (VD) tem um papel importante no desenvolvimento e na manutenção do tecido ósseo. Em níveis normais, ela tem efeito positivo sobre volume, qualidade óssea, bem como sua densidade. Considerando o grande número de pessoas que apresentam alterações séricas da mesma, esta pesquisa visa observar a taxa de hipovitaminose D (hD) na população estudada e os fatores que podem influenciar na incidência de hD, e avaliar a influência da hD nas condições clínica e radiográfica peri-implantar. Todos os participantes dos grupos foram submetidos a um Questionário de Frequência Alimentar Semi-quantitativo sobre a ingestão de cálcio alimentar (QFASQ), visando avaliar os fatores de risco. Os pacientes foram submetidos a exames laboratoriais de dosagem de 25- hidroxivitamina D, aqueles que apresentaram uma dosagem sérica de VD inferior a 30ng/mL foram alocados no grupo anormal (insuficiente ou deficiente) e os participantes com dosagem igual ou acima de 30ng/mL foram alocados ao grupo normal (suficiente). Os participantes receberam as seguintes avaliações: análise clínica peri-implantar (profundidade de sondagem, largura da mucosa queratinizada, índice de sangramento do sulco modificado, índice de placa modificado), análise radiográfica (distância entre a cervical do implante e as cristas ósseas mesial e distal). Os pacientes que foram alocados no grupo anormal foram submetidos à reposição da VD, e após a reposição, uma nova analise clinica e radiográfica foi realizada. Constatou-se que na população inicial do estudo cerca 36% dos indivíduos tinham hD. Quanto ao questionário alimentar, menor quantidade de ingestão de derivados do leite, como o iogurte e a menor frequência de atividades físicas mostraram maior risco para uma hD. A análise clinica demonstrou que VD se comportou, em relação aos parâmetros peri-implantares, de forma não significativa, estatisticamente, para profundidade de sondagem, largura de mucosa queratinizada, índice de placa modificado e para índice de sangramento modificado entre os 2 períodos. Concluiu-se que menos da metade da amostra apresentou hD e os alimentos ricos em cálcio podem contribuir para níveis séricos de VD normais. A VD não influenciou nos parâmetros clínicos peri-implantares estudados.

Made available in DSpace on 2014-08-20T14:37:58Z (GMT). No. of bitstreams: 1 tese_eduardo_schmitt.pdf: 454020 bytes, checksum: 6587a158d6c433744bdf8a0800971c6d (MD5) Previous issue date: 2009-11-12 / Three experiments were designed based in evidences that the calcium have the important role in the energetic metabolism of ruminants. The first experiment tested the possibility of use the Ca2Cl as diagnostic in impaired of insulin secretion and glucose metabolism in pregnant ewes. In the others two we researched the hypocalcemia effects in the metabolic profile of dairy cows in good body score condition during prepartum and ewes that were in chronic negative energetic balance. The calcium infusion during the late gestation seems no change insulin secretion and glucose metabolism during the glucose tolerance test. However, new investigation about the form of administration and the dose to ruminant need to be review. In dairy cows that were in good body condition score in prepartum the hypocalcemia seem has been responsible to change the energetic status. Nevertheless hypocalcaemic ewes that were in chronic negative energetic balance, the energy status was not changed. These founds suggest that the hypocalcemia could be responsible to induce the negative energetic balance in ruminants, but this effect may be dependent of adaptations conditions in the prepartum. / Com base em evidências de que o cálcio exerce um papel importante no metabolismo energético de ruminantes, foram conduzidos três experimentos. O primeiro experimento testou a possibilidade do uso da infusão de Ca2Cl para diagnóstico de alterações na secreção de insulina e no metabolismo da glicose em ovelhas prenhes durante o teste de tolerância à glicose. Nos outros dois experimentos foam investigados os efeitos da hipocalcemia no perfil metabólico de vacas leiteiras com boa condição corporal no pré-parto e de ovelhas que estavam em balanço energético negativo crônico (BENC). A infusão de Ca2Cl durante o final da gestação não modificou os padrões de secreção de insulina e metabolização de glicose durante o teste de tolerância à glicose. Entretanto novas investigações são necessárias quanto à forma de administração e a dose utilizada em ruminantes. Nas vacas leiteiras que estavam em bom estado corporal no pré-parto, a hipocalcemia teve influência na condição energética destes animais. No entanto, em ovelhas que foram induzidas à hipocalcemia, e que estavam em BENC, a condição energética não foi alterada. Os resultados permitem inferir que a hipocalcemia pode ser responsável por induzir o balanço energético negativo em ruminantes, porém este efeito parece ser dependente de adaptações metabólicas ligadas ao status nutricional do pré-parto, já que quando estabelecido o BENC, a hipocalcemia não aleterou os metabólitos ligados ao status energético.

O receptor sensor do cálcio (CASR) desempenha um importante papel na manutenção da concentração plasmática do cálcio. Desde a sua descrição, mais de 200 mutações foram descritas podendo levar à perda ou ao ganho de função, resultando em situações de hiper ou hipocalcemia, respectivamente. Mutações inativadoras estão associadas à hipercalcemia hipocalciúrica familiar (HHF) e ao hiperparatireoidismo neonatal grave (HPTNG), enquanto que mutações ativadoras estão associadas à hipocalcemia autossômica dominante (HAD) e à Síndrome de Bartter tipo V. O objetivo deste estudo foi realizar o diagnóstico molecular, por meio da análise do gene CASR, em pacientes com HPTNG, HHF, hipocalcemia com PTH inapropriadamente normal ou baixo e hipoparatireoidismo idiopático com hipercalciúria na vigência de tratamento. Para cada criança (n = 2) com diagnóstico clínico e laboratorial de HPTNG, uma mutação \"nonsense\" em homozigose foi identificada na região codificadora do CASR (p.E519X e p.R544X). O estudo molecular dos pais das crianças mostrou tratar-se de casos herdados caracterizando-os como indivíduos com HHF e possibilitou o aconselhamento genético para estas famílias. Mutações pontuais em heterozigose na região codificadora do CASR (p.R25X, p.R69H, p.T627I) foram detectadas em três dos quatro pacientes selecionados com diagnóstico inicial de hiperparatireoidismo primário e bioquímica compatível com hipercalcemia hipocalciúrica. Estes achados constituem a base molecular da HHF e permitiram o rastreamento de outros casos de HHF nas respectivas famílias com impacto na abordagem terapêutica dos mesmos. Na paciente em que não foi detectada nenhuma mutação na região codificadora do CASR, o estudo prosseguiu com a pesquisa de alterações no número de cópias gênicas e de mutações nas regiões promotoras P1 e P2 como possíveis causas do fenótipo em questão. O resultado destas abordagens foi normal. Dos quatro pacientes selecionados com quadro de hipoparatireoidismo idiopático e hipercalciúria na vigência de tratamento, em apenas uma, a causa molecular foi definida por mutação \"missense\" em heterozigose na região codificadora do CASR (p.E767K) repercutindo positivamente no seu tratamento. Nos demais casos (n = 3), a pesquisa de alterações no número de cópias gênicas e de mutações nas regiões promotoras P1 e P2 também resultou normal. / The calcium sensing receptor (CASR) plays an important role in maintaining the plasma concentration of calcium. From its first description, more than 200 mutations have been described leading to loss or gain of function, resulting in conditions of either hyper or hypocalcemia, respectively. Inactivating mutations are associated with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), whereas activating mutations are associated with autosomal dominant hypocalcemia (ADH) and type V Bartter\'s syndrome. The aim of this study was to perform the molecular diagnosis, by analyzing the CASR gene, in patients with NSHPT, FHH, hypocalcemia with inappropriately normal or low PTH and idiopathic hypoparathyroidism with hypercalciuria during treatment. In every child (n = 2) with clinical and laboratory diagnosis of NSHPT, a nonsense mutation in homozygosity was identified in the coding region of the CASR (p.E519X and p.R544X). The molecular analysis of the child\'s parents showed that they were inherited cases qualifying them as individuals with FHH and it enabled a genetic counseling for these families. Point mutations in heterozygosity in the coding region of the CASR (p.R25X, p.R69H, p.T627I) have been detected in three out of the four selected patients with an initial diagnosis of primary hyperparathyroidism and biochemistry compatible with hypocalciuric hipercalcemia. These findings are the molecular basis of FHH and allowed the screening of other FHH cases in these families impacting on their therapeutic approach. In patients where no mutation in the coding region of the CASR was detected, the study went on researching for changes in the number of gene copies and mutations in P1 and P2 promoter regions as possible causes to the phenotype in question. The result of these approaches has been normal. The molecular cause has been defined as missense mutation in heterozygosis in the coding region of the CASR (p.E767K) in only one out of the four selected patients with idiopathic hypoparathyroidism and hypercalciuria during treatment, with a positive impact on her treatment. In the other cases (n = 3), the search for changes in the number of gene copies and mutations in the P1 and P2 promoter regions was normal.