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1.
J Vet Intern Med ; 38(4): 2257-2264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946311

RESUMO

BACKGROUND: Little information exists about vitamin D status in bitches with mammary tumors. OBJECTIVES: To determine whether low plasma vitamin D concentrations are found in bitches with mammary tumors. ANIMALS: Eighty-five client-owned bitches with mammary tumors (n = 21 benign, n = 64 malignant) and 39 age-matched healthy bitches. METHODS: Case-control study. Plasma ionized and total calcium, phosphorus, magnesium, urea, creatinine, albumin, total proteins, alanine aminotransferase, alkaline phosphatase, parathyroid hormone (PTH), calcitriol (1,25-dihydroxyvitamin D), and 25-hydroxyvitamin D concentrations were measured in all bitches at the time of clinical diagnosis and before any treatments. Statistical analysis was performed to compare variables among groups (control, benign, and malignant). RESULTS: No significant differences were found when plasma 25-hydroxyvitamin D concentrations in bitches with malignant (148.9 [59.9] ng/mL) and benign mammary tumors (150.1 [122.3] ng/mL) were compared with control group (129.9 [54.5] ng/mL). Parathyroid hormone was significantly higher in bitches with malignant (19.9 [20.5] pg/mL), and benign mammary tumors (14.6 [14.9] pg/mL) compared with control group (7.5 [7.5] pg/mL; P < .01). Only the presence of mammary tumors (P < .01) and age (P = .04; adjusted R2 = .22) was significant in predicting PTH. CONCLUSIONS: Bitches with mammary tumors do not have low 25-hydroxyvitamin D concentrations thus vitamin D supplementation is unlikely to be useful for prevention of mammary tumors in bitches.


Assuntos
Doenças do Cão , Neoplasias Mamárias Animais , Hormônio Paratireóideo , Vitamina D , Animais , Cães , Feminino , Doenças do Cão/sangue , Neoplasias Mamárias Animais/sangue , Vitamina D/sangue , Vitamina D/análogos & derivados , Estudos de Casos e Controles , Hormônio Paratireóideo/sangue , Cálcio/sangue , Fósforo/sangue
2.
Sci Rep ; 10(1): 1795, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020002

RESUMO

To test the hypothesis that fibroblast growth factor 23 (FGF23) is directly regulated by energy intake, in vivo and in vitro experiments were conducted. Three groups of rats were fed diets with high (HC), normal (NC) and low (LC) caloric content that resulted in different energy intake. In vitro, UMR106 cells were incubated in high (HG, 4.5 g/l) or low glucose (LG, 1 g/l) medium. Additional treatments included phosphorus (P), mannitol, rapamycin and everolimus. Intestinal absorption of P and plasma P concentrations were similar in the three groups of rats. As compared with NC, plasma FGF23 concentrations were increased in HC and decreased in the LC group. A significant correlation between energy intake and plasma FGF23 concentrations was observed. In vitro, mRNA FGF23 was significantly higher in UMR106 cells cultured in HG than in LG. When exposed to high P, mRNA FGF23 increased but only when cells were cultured in HG. Cells incubated with HG and mechanistic target of rapamycin (mTOR) inhibitors expressed low mRNA FGF23, similar to the values obtained in LG. In conclusion, this study shows a direct regulation of FGF23 production by energy availability and demonstrates that the mTOR signaling pathway plays a central role in this regulatory system.


Assuntos
Ingestão de Energia/fisiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Glucose/farmacologia , Fósforo/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Ratos , Ratos Wistar
3.
Kidney Int ; 95(5): 1064-1078, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878213

RESUMO

Calcimimetics decrease parathyroid hormone (PTH) secretion in patients with secondary hyperparathyroidism. The decrease in PTH should cause a reduction in bone turnover; however, the direct effect of calcimimetics on bone cells, which express the calcium-sensing receptor (CaSR), has not been defined. In this study, we evaluated the direct bone effects of CaSR activation by a calcimimetic (AMG 641) in vitro and in vivo. To create a PTH "clamp," total parathyroidectomy was performed in rats with and without uremia induced by 5/6 nephrectomy, followed by a continuous subcutaneous infusion of PTH. Animals were then treated with either the calcimimetic or vehicle. Calcimimetic administration increased osteoblast number and osteoid volume in normal rats under a PTH clamp. In uremic rats, the elevated PTH concentration led to reduced bone volume and increased bone turnover, and calcimimetic administration decreased plasma PTH. In uremic rats exposed to PTH at 6-fold the usual replacement dose, calcimimetic administration increased osteoblast number, osteoid surface, and bone formation. A 9-fold higher dose of PTH caused an increase in bone turnover that was not altered by the administration of calcimimetic. In an osteosarcoma cell line, the calcimimetic induced Erk1/2 phosphorylation and the expression of osteoblast genes. The addition of a calcilytic resulted in the opposite effect. Moreover, the calcimimetic promoted the osteogenic differentiation and mineralization of human bone marrow mesenchymal stem cells in vitro. Thus, calcimimetic administration has a direct anabolic effect on bone that counteracts the decrease in PTH levels.


Assuntos
Compostos de Bifenilo/administração & dosagem , Remodelação Óssea/efeitos dos fármacos , Calcimiméticos/administração & dosagem , Hiperparatireoidismo Secundário/tratamento farmacológico , Falência Renal Crônica/complicações , Fenetilaminas/administração & dosagem , Animais , Modelos Animais de Doenças , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Masculino , Osteoblastos/efeitos dos fármacos , Hormônio Paratireóideo/administração & dosagem , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Ratos , Ratos Wistar , Receptores de Detecção de Cálcio/metabolismo
4.
PLoS One ; 12(10): e0185981, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28982165

RESUMO

Treatment of canine leishmaniasis (CanL) represents a challenge. Due to the high prevalence of renal disease associated to CanL, it is important to find an effective drug that does not damage the kidneys. Marbofloxacin has been shown to be effective and well tolerated in non-azotemic dogs with leishmaniasis. To evaluate the safety and efficacy of marbofloxacin in dogs with leishmaniasis and decreased renal function, 28 dogs suffering from leishmaniasis and chronic kidney disease (CKD) were treated with oral marbofloxacin at 2 mg/Kg/day for 28 days. During treatment dogs were assessed by performing weekly physical exams, measuring blood pressure and evaluating blood and urine parameters. Lymph node aspirations were also obtained at days 0 and 28. The global clinical score decreased significantly, from 6.2±3.4 to 4.7±3.1 (p = 0.0001), after treatment. Marbofloxacin also decreased parasitic load in 72% of the dogs. No significant differences in plasma creatinine, urine specific gravity, urinary concentrations of cystatin C, ferritin and urinary protein loss were detected during treatment. A transient but significant decrease in blood pressure was detected up to day 14 (from 180.1±36.6 to 166.0±32.7 mmHg; p = 0.016). Moreover, dogs showed a significant increase in plasma albumin concentration (from 15.0±5.2 to 16.6±3.9 g/L; p = 0.014) and a significant decrease in globulin concentration (from 59.0±18.1 to 54.1±18.0 g/L; p = 0.005). The results demonstrate that, in addition to being effective for treatment of CanL, marbofloxacin is a very safe drug in dogs with CKD and leishmaniasis.


Assuntos
Fluoroquinolonas/uso terapêutico , Nefropatias/veterinária , Leishmaniose/veterinária , Animais , Pressão Sanguínea , Cães , Feminino , Nefropatias/complicações , Nefropatias/fisiopatologia , Testes de Função Renal , Leishmaniose/complicações , Leishmaniose/tratamento farmacológico , Leishmaniose/fisiopatologia , Masculino , Carga Parasitária , Reação em Cadeia da Polimerase em Tempo Real
5.
PLoS One ; 11(5): e0156331, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27243456

RESUMO

To document the biochemical and pathologic features of vitamin D intoxication in lynx and to characterize mineral metabolism in healthy lynx, blood samples were obtained from 40 captive lynx that had been receiving excessive (approximately 30 times the recommended dose) vitamin D3 in the diet, and from 29 healthy free ranging lynx. Tissue samples (kidney, stomach, lung, heart and aorta) were collected from 13 captive lynx that died as a result of renal disease and from 3 controls. Vitamin D intoxication resulted in renal failure in most lynx (n = 28), and widespread extraskeletal calcification was most severe in the kidneys and less prominent in cardiovascular tissues. Blood minerals and calciotropic hormones in healthy lynx were similar to values reported in domestic cats except for calcitriol which was higher in healthy lynx. Changes in mineral metabolism after vitamin D intoxication included hypercalcemia (12.0 ± 0.3 mg/dL), hyperphosphatemia (6.3 ± 0.4 mg/dL), increased plasma calcidiol (381.5 ± 28.2 ng/mL) and decreased plasma parathyroid hormone (1.2 ± 0.7 pg/mL). Hypercalcemia and, particularly, hyperphosphatemia were of lower magnitude that what has been previously reported in the course of vitamin D intoxication in other species. However, extraskeletal calcifications were severe. The data suggest that lynx are sensitive to excessive vitamin D and extreme care should be taken when supplementing this vitamin in captive lynx diets.


Assuntos
Lynx/metabolismo , Insuficiência Renal/veterinária , Vitamina D/toxicidade , Animais , Animais de Zoológico , Calcinose/induzido quimicamente , Calcinose/metabolismo , Calcinose/veterinária , Gatos , Suplementos Nutricionais/toxicidade , Espécies em Perigo de Extinção , Feminino , Masculino , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/metabolismo , Vitamina D/administração & dosagem , Vitamina D/sangue
6.
J Feline Med Surg ; 15(10): 866-71, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23413272

RESUMO

The purpose of this study was to describe changes in calcium, phosphorus, magnesium, parathyroid hormone, calcitriol and calcidiol in cats from 3 to 15 months of age. Fourteen European shorthair healthy cats of both sexes (seven males, seven females) belonging to a research colony were studied from 3 to 15 months of age. Plasma concentrations of total calcium, ionised calcium, albumin, phosphorus, magnesium, intact parathyroid hormone (I-PTH), whole parathyroid hormone (W-PTH), calcidiol and calcitriol were measured at 3, 6, 9, 12 and 15 months of age. From 3 months of age to adulthood cats showed a decrease in calcium (both total and ionised), phosphorus and magnesium. No major changes in PTH were evident, although the ratio of W-PTH:I-PTH decreased significantly with age. A reciprocal change in vitamin D metabolites (decrease in calcitriol and increase in calcidiol) was identified during the growing process. Our results, showing changes in most parameters of mineral metabolism during growth, reinforce the need to use adequate age-related reference values for diagnostic purposes.


Assuntos
Envelhecimento/fisiologia , Gatos/crescimento & desenvolvimento , Gatos/metabolismo , Minerais/metabolismo , Animais , Calcifediol/sangue , Calcifediol/metabolismo , Calcitriol/sangue , Calcitriol/metabolismo , Gatos/sangue , Feminino , Masculino , Minerais/sangue , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Valores de Referência
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