RESUMEN
Vitamin D is a water-insoluble compound presented in two main forms (D2 and D3), susceptible to environmental conditions. Microencapsulation is an alternative to supplements and preserve vitamin D properties in foods. Entrapment efficiency (EE) is the main property to evaluate the encapsulation effectiveness and therefore it is of interest the study of analytical methods for the identification and quantification of this compound within the particle. This paper describes a low cost UV-Vis methodology validation to the identification and quantification of vitamin D3 in microparticles produced by hot homogenization. The method was validated following the International Conference on Harmonization (ICH) guidelines. To guarantee safe application in foodstuff, microparticles toxigenicity was evaluated with Allium cepa L. in vivo model, showing no cytotoxic nor genotoxic potential. High entrapment efficiency was obtained, the results also demonstrated that the concentration of vitamin D3 in microparticles can be safely accessed by the validated method.
Asunto(s)
Colecalciferol/análisis , Colecalciferol/toxicidad , Suplementos Dietéticos/análisis , Análisis de los Alimentos/métodos , Microesferas , Colecalciferol/química , Contaminación de Alimentos/análisis , Cebollas/químicaRESUMEN
Knowledge about complications of chronic ultra-high dose vitamin D supplementation is limited. We report a patient with primary progressive multiple sclerosis (MS) who presented with generalized weakness caused by hypercalcemia after uncontrolled intake of more than 50,000 IU of cholecalciferol per day over several months. Various treatment strategies were required to achieve normocalcemia. However, renal function improved only partly and further progression of MS was observed. We conclude that patients need to be informed about the risks of uncontrolled vitamin D intake and neurologists need to be alert of biochemical alterations and symptoms of vitamin D toxicity.
Asunto(s)
Colecalciferol/toxicidad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hipercalcemia/inducido químicamente , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Vitaminas/toxicidad , Colecalciferol/administración & dosificación , Humanos , Hipercalcemia/complicaciones , Masculino , Persona de Mediana Edad , Insuficiencia Renal/etiología , Vitaminas/administración & dosificaciónRESUMEN
El objetivo de esta nota técnica es la descripción y comentarios de un caso clínico reciente de intoxicación por sobredosificación por vitamina D, y la correcta interpretación clínica y de los parámetros de laboratorio. Caso clínico. Lactante de 6 meses en tratamiento con Biominol® (suplemento vitamínico), ingresó debido a un estado de decaimiento e irritabilidad. Las analíticas iniciales muestran concentraciones de calcio iónico en sangre de 2,11mmol/L (intervalo de referencia (IR): 1,15-1,29mmol/L), y concentración de calcio total plasmático de 5,5mmol/L (IR: 2,25-2,75mmol/L). En nuestro laboratorio, las vitaminas D2 y D3 fueron determinadas por cromatografía líquida de alta resolución (HPLC), y por un método electroquimioluminiscente, que mide la vitamina D total. Los valores de vitamina D2 fueron 419ng/mL y vitamina D total 482ng/mL (IR: 30-100ng/mL). La intoxicación de vitamina D tuvo origen exógeno, debido al incremento de vitamina D2. El diagnóstico definitivo fue hipercalcemia severa secundaria a intoxicación por vitamina D y nefrocalcinosis secundaria a esta con función renal normal con hipercalciuria. Como conclusión, cabe destacar la importancia de la correcta dosificación de los pacientes y la determinación de las diferentes formas de vitamina D para averiguar su origen, realizando una correcta interpretación (AU)
The objective of this technical note describes and comments on a recent clinical case of poisoning by overdose of vitamin D, and the correct interpretation of clinical and laboratory parameters. Vitamin D is a fat-soluble vitamin involved in the absorption of calcium and phosphorus in the intestine. Administration of high doses for prolonged periods can cause hypercalcemia, leading to kidney failure and renal calcifications. Clinical case. The definitive diagnosis of this patient was severe hypercalcemia secondary to exogenous vitamin D poisoning, and nephrocalcinosis secondary to this with normal renal function with hypercalciuria. In conclusion, the correct dosing of patients and determination of different forms of vitamin D to trace its origin and making a correct interpretation is important. Male, 6 months old in treatment with Biominol® (vitamin D supplement), was admitted to the emergency department because of a state of decline and irritability. The initial analytical results showed an ionized calcium concentration in blood of 2.11mmol/L (reference interval (RI): 1.15 - 1.29mmol/L), and plasma total calcium concentration of 5.5mmol/L (RI: 2.25-2.75mmol/L). In our laboratory, Vitamin D2 and D3 were determined by liquid chromatography high resolution (HPLC), and an electrochemiluminescence method. The results showed a vitamin D2 419ng/mL and total vitamin D 482ng/mL (RI: 30-100ng/mL). It was found that the vitamin D overdose was of exogenous origin, due to increased vitamin D2 (AU)
Asunto(s)
Humanos , Masculino , Lactante , Sobredosis de Droga/complicaciones , Sobredosis de Droga/terapia , Vitamina D/administración & dosificación , Vitamina D/efectos adversos , Diuresis/fisiología , Cromatografía , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión , Peso por Estatura/fisiología , Electrocardiografía , Diuresis , Ergocalciferoles/toxicidad , Colecalciferol/toxicidadRESUMEN
A reliable, accurate and reproducible method to quantify vitamin D3 (Vit. D3) in oily dietary supplements was developed after three Vit. D3 intoxications were diagnosed as reasonably resulting from a dietary administration of a cod liver oil based supplement. Liquid chromatography coupled to mass spectrometry operating in atmospheric pressure chemical ionization conditions (LC-APCI) and by using a deuterium labelled internal standard resulted to be an effective technique to reach the analytical aim. Due to the complexity of the oily matrix, the new analytical approach required a solid phase extraction step prior to analysis. The amount of Vit. D3 declared on the label of the cod liver oil based supplement for each soft capsule is 1.5µg. Consequently, the method was developed to quantify Vit. D3 amounts in the range 1-5µg/mL. To improve reliability of obtained data, both MS and MS/MS acquisition methods were employed. The method was evaluated by measuring the characteristic parameters such as linearity, precision, accuracy and robustness and cross checked against a certified pharmaceutical preparation. The LC-APCI-MS and MS/MS methods were applied in order to assess the Vit. D3 content in the dietary supplements taken by the intoxicated patients, found about three order of magnitude higher than that declared. The Vit. D3 content of other batches of the same commercial product was found as declared.
Asunto(s)
Colecalciferol/análisis , Aceite de Hígado de Bacalao/química , Suplementos Dietéticos/análisis , Inspección de Alimentos/métodos , Colecalciferol/química , Colecalciferol/toxicidad , Cromatografía Líquida de Alta Presión , Suplementos Dietéticos/toxicidad , Etiquetado de Alimentos , Inocuidad de los Alimentos , Humanos , Espectrometría de Masas/métodos , Trastornos Nutricionales/inducido químicamente , Trastornos Nutricionales/etiología , Reproducibilidad de los Resultados , Extracción en Fase SólidaRESUMEN
Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K), and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D(3). Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.
Asunto(s)
Colecalciferol/toxicidad , Hidroclorotiazida/uso terapéutico , Hipercalciuria/tratamiento farmacológico , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Animales , Calcio/uso terapéutico , Calcio/orina , Canales de Calcio/genética , Canales de Calcio/metabolismo , Hipercalciuria/inducido químicamente , Ratas , Ratas Sprague-Dawley , Transportador 1 de Sodio-Glucosa/genética , Transportador 1 de Sodio-Glucosa/metabolismo , Intercambiador 3 de Sodio-Hidrógeno , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/metabolismo , Simportadores de Cloruro de Sodio-Potasio/genética , Simportadores de Cloruro de Sodio-Potasio/metabolismo , Miembro 1 de la Familia de Transportadores de Soluto 12 , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismoRESUMEN
Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K), and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D3. Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.
Asunto(s)
Animales , Ratas , Calcio/uso terapéutico , Canales de Calcio/genética , Colecalciferol/toxicidad , Hidroclorotiazida/uso terapéutico , Hipercalciuria/inducido químicamente , Ratas Sprague-Dawley , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Transportador 1 de Sodio-Glucosa/genética , Intercambiadores de Sodio-Hidrógeno/genética , Simportadores de Cloruro de Sodio-Potasio/genética , Canales Catiónicos TRPV/genéticaRESUMEN
The tolerable upper intake level (UL) for vitamin D is 50 mcg/d (2000 iu/d) in North America and in Europe. In the United Kingdom a guidance level exists for vitamin D, 25 mcg/d (1000 iu/d), defined as the dose "of vitamins and minerals that potentially susceptible individuals could take daily on a life-long basis, without medical supervision in reasonable safety." Exposure of skin to sunshine can safely provide an adult with vitamin D in an amount equivalent to an oral dose of 250 mcg/d. The incremental consumption of 1 mcg/d of vitamin D3 raises serum 25-hydroxyvitamin D [25(OH)D ] by approximately 1 nmol/L (0.4 microg/L). Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L (200 microg/L). Older adults are advised to maintain serum 25(OH)D concentrations >75 nmol/L. The preceding numbers indicate that vitamin D3 intake at the UL raises 25(OH)D by approximately 50 nmol/L and that this may be more desirable than harmful. The past decade has produced separate North American, European, and U.K. reports that address UL or guidance-level values for vitamin D. Despite similar well-defined models for risk assessment, each report has failed to adapt its message to new evidence of no adverse effects at higher doses. Inappropriately low UL values, or guidance values, for vitamin D have hindered objective clinical research on vitamin D nutrition, they have hindered our understanding of its role in disease prevention, and restricted the amount of vitamin D in multivitamins and foods to doses too low to benefit public health.
Asunto(s)
Política Nutricional , Necesidades Nutricionales , Vitamina D/administración & dosificación , Adulto , Animales , Calcifediol/sangre , Calcifediol/toxicidad , Colecalciferol/administración & dosificación , Colecalciferol/toxicidad , Suplementos Dietéticos , Alimentos Fortificados , Humanos , Hipercalcemia/inducido químicamente , Luz Solar , Deficiencia de Vitamina D/prevención & controlRESUMEN
Ghrelin is a new peptide with regulatory actions in growth hormone secretion in the anterior pituitary gland and in energy metabolism. Currently, ghrelin has potently protective effects in cardiovascular diseases. We used an in vivo model of rat vascular calcification induced by vitamin D3 and nicotine and one of cultured rat vascular smooth muscular cells (VSMCs) calcification induced by beta-glycerophosphate to study the possible mechanism in the regulatory action of ghrelin in vascular calcification. Calcification increased total Ca2+ content and 45Ca2+ deposition in aortas and VSMCs and alkaline phosphatase (ALP) activation in plasma, aortas and VSMCs. However, calcified aortas and VSMCs showed a significant decrease in osteopontin (OPN) mRNA expression and a marked reduction of ghrelin levels in plasma and its mRNA expression in aortas. The aortic calcification was significantly attenuated by subcutaneous administration of ghrelin 30 and 300 nmol kg(-1) day(-1) for 4 weeks, and the latter dosage was more potent than the former. Ghrelin treatment at the two dosages reduced the total aorta Ca2+ content by 24.4% and 28.1%, aortic 45Ca2+ deposition by 18.4% and 24.9%, plasma ALP activity by 36.6% and 76.7%, and aortic ALP activity by 10.3% and 47.6% (all P < 0.01 or 0.05), respectively. Ghrelin at 10(-8)-10(-6) mol/L attenuated the calcification in cultured VSMCs, with decreased total Ca2+ content, 45Ca2+ deposition and ALP activity and increased OPN mRNA expression, in a concentration-dependent manner. In addition, endothelin levels in plasma and aortas and its mRNA expression in aortas significantly increased with calcification, but ghrelin treatment significantly decreased endothelin levels and mRNA expression, with the high dosage being more potent than the lower dosage. These results indicate that local ghrelin in vascular was down-regulated during vascular calcification, whereas administration of ghrelin effectively attenuated vascular and VSMCs calcification.
Asunto(s)
Aorta/metabolismo , Calcinosis/tratamiento farmacológico , Músculo Liso Vascular/metabolismo , Hormonas Peptídicas/administración & dosificación , Animales , Aorta/patología , Calcinosis/inducido químicamente , Calcinosis/metabolismo , Células Cultivadas , Colecalciferol/toxicidad , Ghrelina , Masculino , Músculo Liso Vascular/patología , Nicotina/toxicidad , Agonistas Nicotínicos/toxicidad , RatasRESUMEN
Time-dependent differences in adverse reactions and efficacy by a repeated administration of 1,25(OH)2 vitamin D3 (vit D, 0.3 microg/Kg/day for 12 weeks) were examined in 5/6 nephrectomized rats under a condition of 12-hour light-dark cycle. The 5/6 nephrectomy increased serum concentrations of phosphate, osteocalcin and PTH, and urinary excretions of phosphate and deoxypyridinoline (DPD) while the maneuver reduced serum Ca concentration and its urinary excretion. Animals with a dosing of the drug at 2 hours after light on (HALO) had more grade of hypercalcemia and hyperphosphatemia than those at 14 HALO. Reduction of serum intact PTH and increase of serum vit D were observed in both groups with a similar extent. Increase of osteocalcin by the drug was greater in 14 HALO trial. Urinary excretion of DPD was not influenced by the treatment. The increase in bone density of femur was greater in 14 HALO than in 2 HALO trials. These results suggest that adverse reactions of vit D were ameliorated and its efficacy was enhanced after the repeated dosing of the drug at 14 HALO. Time-dependent variation in the sensitivity of the drug to osteoblast was involved in the mechanism of these events, while the roles of pharmacokinetic alteration and renal response were small, if any.
Asunto(s)
Colecalciferol/farmacología , Colecalciferol/toxicidad , Nefrectomía , Aminoácidos/orina , Animales , Biomarcadores/orina , Peso Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Calcio/sangre , Calcio/orina , Colecalciferol/administración & dosificación , Creatinina/metabolismo , Masculino , Osteocalcina/metabolismo , Hormona Paratiroidea/metabolismo , Fósforo/sangre , Fósforo/orina , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
The objectives of this study were to develop a novel approach to postmortem diagnosis of cholecalciferol (CCF) toxicosis in dogs using kidney, bile, and urine samples, and to differentiate CCF from ethylene glycol (EG) toxicosis. To achieve these objectives, specimens collected from 2 previous laboratory studies in which dogs were given a single oral toxic dose of CCF (8.0 mg/kg) were used. For EG toxicosis, historical data from the previous 13 years (1985-1998) were reviewed and confirmed cases of EG toxicosis were selected. The historical data were used to compare trace mineral concentrations, specifically of calcium and phosphorus to differentiate between intoxications caused by CCF from that caused by EG in dogs. Kidneys, bile, and urine from dogs that died of CCF toxicosis were analyzed for 25 monohydroxy vitamin D3 (25(OH)D3) and 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) and compared to known control unexposed dogs. Results of this study show that biliary and renal 25(OH)D3 concentrations and renal calcium to phosphorus ratio are of diagnostic value in dogs exposed to toxic concentrations of CCF. The renal calcium to phosphorus ratio was <0.1 in normal dogs, 0.4-0.9 in dogs that died of CCF toxicosis, and >2.5 in dogs that died of EG toxicosis.
Asunto(s)
Colecalciferol/toxicidad , Enfermedades de los Perros/diagnóstico , Glicol de Etileno/toxicidad , Animales , Bilis/química , Calcio/análisis , Colecalciferol/análisis , Diagnóstico Diferencial , Perros , Hipercalcemia/etiología , Hipercalcemia/veterinaria , Riñón/química , Fósforo/análisis , Distribución Tisular , Urinálisis/veterinariaRESUMEN
OBJECTIVE: To determine whether pamidronate disodium can reduce cholecalciferol-induced toxicosis in a dose-related manner. ANIMALS: 20 clinically normal, 8- to 12-month-old male Beagles. PROCEDURE: All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were randomly assigned to 4 groups of 5 dogs each. Dogs were treated with IV administration of 0.9% NaCl solution (SC group), 0.65 mg of pamidronate/kg in 0.9% NaCl solution (LP group), 1.3 mg of pamidronate/kg in 0.9% NaCl solution (MP group), or 2.0 mg of pamidronate/kg in 0.9% NaCl solution (HP group) on days 1 and 4 after administration of CCF. Dogs were observed for 14 days, and serial blood samples were collected for serum biochemical, electrolyte, and 25-hydroxyvitamin D3 analyses. Urine samples were collected for determination of specific gravity. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Histologic examination of renal tissue was performed. RESULTS: One dog in the SC group was euthanatized 3 days after administration of CCF because of severe clinical signs of toxicosis. Dogs in the HP group had significantly higher mean GFR (day 3), serum potassium concentrations (day 14), and urine specific gravity (days 7 and 14) and significantly lower mean serum creatinine concentrations and total calcium X phosphorus concentration product (days 4 and 7) than dogs in the SC group. Dogs in the HP group had no abnormal findings on histologic examination of renal tissue, dogs in the LP and MP groups had trace to mild mineralization of renal tissue, and dogs in the SC group had moderate mineralization and cellular necrosis of proximal renal tubules. CONCLUSIONS AND CLINICAL RELEVANCE: Pamidronate disodium is a potentially useful drug to reduce CCF-induced toxicosis and other causes of hypercalcemia associated with increased bone resorption in dogs.
Asunto(s)
Antiinflamatorios/uso terapéutico , Colecalciferol/toxicidad , Difosfonatos/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Animales , Calcio/sangre , Colecalciferol/sangre , Creatinina/sangre , Enfermedades de los Perros/inducido químicamente , Perros , Relación Dosis-Respuesta a Droga , Tasa de Filtración Glomerular/veterinaria , Corteza Renal/patología , Masculino , Pamidronato , Fósforo/sangre , Potasio/sangre , Distribución Aleatoria , Sodio/sangre , Gravedad Específica , Urea/sangre , Orina/químicaAsunto(s)
Enfermedades de los Animales/inducido químicamente , Enfermedades de los Animales/tratamiento farmacológico , Calcio/sangre , Colecalciferol/toxicidad , Enfermedades de los Animales/diagnóstico , Enfermedades de los Animales/patología , Animales , Diagnóstico Diferencial , Interacciones Farmacológicas , Fósforo/sangreRESUMEN
Kampo medicine is a traditional Japanese therapeutic system which originated in China and was used to treat various diseases for hundreds of years. Kampo medicine had been also used for the cure and the prevention of urinary calculi for many years, but the effect and the mechanism of this use of kampo medicine are unclear. We examined the inhibitory effect of the kampo medicine takusha on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) and vitamin D3 in rats. We also investigated the effect of takusha on osteopontin (OPN) expression, which we previously identified as an important stone matrix protein. The control group rats were non-treated; the stone group rats were administered EG and vitamin D3, and the takusha group was administered takusha in addition to EG and vitamin D3. The rate of renal stone formation was lower in the takusha group than in the stone group; thus, the OPN expression in the takusha group was smaller than in the stone group. Takusha was effective in preventing oxalate calculi formation and OPN expression in rats. These findings suggest that takusha prevents stone formation including not only calcium oxalate aggregation but also proliferation.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Cálculos Renales/prevención & control , Sialoglicoproteínas/genética , Animales , Oxalato de Calcio/metabolismo , Colecalciferol/administración & dosificación , Colecalciferol/toxicidad , Modelos Animales de Enfermedad , Glicol de Etileno/administración & dosificación , Glicol de Etileno/toxicidad , Expresión Génica/efectos de los fármacos , Cálculos Renales/etiología , Cálculos Renales/metabolismo , Masculino , Osteopontina , Ratas , Ratas WistarRESUMEN
Three experiments were conducted to determine the influence of vitamin A on the utilization and amelioration of toxicity of cholecalciferol (vitamin D3), 25-hydroxycholecalciferol [25-(OH)D3], and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in young broiler chicks. Two levels of vitamin A (1,500 and 45,000 IU/kg or 450 and 13,500 microg) were fed in all experiments. In Experiment 1, chicks were fed six levels of vitamin D3 (0, 5, 10, 20, 40, and 80 microg/kg). High dietary vitamin A decreased bone ash (P < 0.001), and increased the incidence of rickets (P < or = 0.02). Linear and quadratic responses to vitamin D3 levels were significant (P < 0.01) for body weight, bone ash, incidence and severity of rickets, and plasma calcium. In Experiment 2, six levels of 25-(OH)D3 (0, 5, 10, 20, 40, and 80 microg/kg) were added to the basal diet. Adding 25-(OH)D3 increased (P < 0.001) body weight, bone ash, and plasma calcium, and decreased rickets and plasma vitamin A. Adding 25-(OH)D3 overcame the reduction in bone ash produced by high dietary vitamin A showing a significant (P < 0.02) interaction. In Experiment 3, six levels of 1,25-(OH)2D3 (0, 2, 4, 8, 16, and 32 microg/kg) were added to the basal diet. High dietary vitamin A increased (P < 0.01) the incidence and severity of rickets. Adding 1,25-(OH)2D3 increased (P < 0.01) body weight, bone ash, plasma calcium, and reduced rickets and plasma and liver vitamin A. Adding 1,25-(OH)2D3 overcame the reduction in bone ash, and the increase in rickets produced by high vitamin A was significant (P < or = 0.05). These results indicate that high dietary vitamin A (45,000 IU/kg) interferes with the utilization of vitamin D3, 25-(OH)D3 and 1,25-(OH)2D3, increasing the requirement for each of them. Moreover, 45,000 IU/kg of dietary vitamin A ameliorated the potential toxic effects of feeding high levels of vitamin D3, 25-(OH)D3 and 1,25-(OH)2D3 to young broiler chickens. Further work is necessary to find the minimum levels of these vitamins needed to cause these effects.
Asunto(s)
Calcifediol/toxicidad , Calcitriol/toxicidad , Pollos/fisiología , Colecalciferol/toxicidad , Vitamina A/farmacología , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Calcifediol/metabolismo , Calcitriol/metabolismo , Colecalciferol/metabolismo , Estudios de Cohortes , Dieta/veterinaria , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Incidencia , Masculino , Enfermedades de las Aves de Corral/dietoterapia , Enfermedades de las Aves de Corral/epidemiología , Raquitismo/dietoterapia , Raquitismo/epidemiología , Raquitismo/veterinaria , Vitamina A/administración & dosificaciónRESUMEN
The changes in bone metabolism and morphology of chondrocytes in bovine Hyena disease caused by administration of vitamin AD3E premix (V-AD3E) or vitamin A (V-A) were examined. At the each age, 5 calves were used. Among them, Hyena disease was recognized in 3 calves; a calf administered a high dose of V-AD3E premix (V-A 3,000,000, V-D3 300,000, and V-E 1,200 I.U./day), a calf administered a half dose of the V-AD3E premix, and a calf administered only V-A 3,000,000 I.U./day. The remaining calves without Hyena disease were a calf administered only V-D3 300,000 I.U./day and a control calf. Each agent was administered orally for 10 days from 1 week after birth. In the 3 calves with Hyena disease, the bone metabolism in bone histomorphometry of ilium was in the state of low turnover at the age of 50 days. The bone volume was small at the age of 12 months. The epiphysial growth plates of the distal femurs and the proximal tibias partially disappeared and the chondrocyte lacunas in them were flattened. The matrix fibers of epiphysial growth plates were thinner in diameter and higher in density than those of the control calf. In the calf administered only V-D3, the values of bone volume decreased with aging. In conclusion, Hyena disease may be caused by excessive administration of V-A, because hypervitaminosis A suppressed the activity of differentiation and proliferation in chondrocytes and osteoblasts, and excessive administration of V-D3 may promote these actions.
Asunto(s)
Huesos/metabolismo , Huesos/fisiopatología , Enfermedades de los Bovinos , Trastornos del Crecimiento/veterinaria , Placa de Crecimiento/patología , Vitamina E/toxicidad , Vitaminas/toxicidad , Animales , Desarrollo Óseo/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/patología , Bovinos , Colecalciferol/toxicidad , Trastornos del Crecimiento/inducido químicamente , Trastornos del Crecimiento/fisiopatología , Placa de Crecimiento/efectos de los fármacos , Placa de Crecimiento/ultraestructura , Microscopía Electrónica de Rastreo , Valores de Referencia , Vitamina A/toxicidadRESUMEN
Naked mole-rats have no access to obvious sources of vitamin D and therefore have an impoverished vitamin D status. In an investigation into the effects of vitamin D supplementation, inadvertently supraphysiological doses of 130,000 times the normal dose of vitamin D were administered. Within 5 days animals appeared lethargic, with reduced food intake. All but one of the seven animals were killed and blood was collected. Plasma vitamin D metabolites 25(OH)D and 1,25(OH)2D and calcium were determined. Both vitamin D metabolite concentrations exceeded the upper limits of sensitivity of the assays (> 100 ng/ml 25(OH)D and > 210 pg/ml 1,25(OH)2D). Active calcium uptake in the intestine was evident along with concomitant increases in calcium concentration in plasma, bone, and teeth. The remaining animal survived, but showed scab-like formations in the skin around the lower jaw and along the nipple line. X-ray analyses revealed calcium deposition in these cornified regions, although there was no evidence of metastatic calcification in other tissues. Deposition of excess calcium in skin that is regularly sloughed off and in teeth that are continuously worn down and replaced may reduce the vitamin D-induced hypercalcaemia and thus alleviate the effects of vitamin D intoxication.
Asunto(s)
Calcio/metabolismo , Colecalciferol/toxicidad , Roedores , Diente/metabolismo , Animales , Calcinosis/inducido químicamente , Calcinosis/veterinaria , Hipercalcemia/inducido químicamente , Hipercalcemia/veterinaria , Enfermedades de los Roedores/inducido químicamente , Enfermedades de la PielRESUMEN
According to chemical analyses, the development of conventional human coronary artery plaques from "fatty streaks" to "fibrous plaques" and "complicated lesions" is dominated by progressive mural calcium (Ca) incorporation. The atherogenic significance of Ca ions and arterial Ca overload was examined under the influence of nicotine, oxidatively modified low-density lipoproteins, spontaneous hypertension, and an elevated extracellular Ca concentration or vitamin D3. Experiments were carried out either in vitro on cultured medial cells of rats or in vivo on various types of experimental arteriosclerosis of rats. Suitable Ca antagonists (verapamil, diltiazem, nifedipine, or nitrendipine) prevented experimental Ca overload of arterial walls and transmembrane Ca uptake into cultured medial cells produced by risk factors. Thus they protected, in vivo and/or in vitro, against the atherogenic potential of Ca ions, i.e., migration, proliferation, matrix production and intracellular Ca overload of vascular smooth-muscle cells, as well as calcification of elastic fibers. The data indicate that various Ca-consuming processes demand a progressive uptake of Ca into arterial walls if Ca-dominated types of arteriosclerosis develop. Under experimental conditions, specific Ca antagonists inhibit Ca-mediated arteriosclerotic alterations by preventing progressive mural Ca incorporation.
Asunto(s)
Arteriosclerosis/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Calcio/metabolismo , Vasos Coronarios/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Animales , Arteriosclerosis/etiología , Arteriosclerosis/prevención & control , Bloqueadores de los Canales de Calcio/farmacología , Células Cultivadas , Colecalciferol/toxicidad , Colesterol/metabolismo , Vasos Coronarios/patología , Diltiazem/farmacología , Diltiazem/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Persona de Mediana Edad , Músculo Liso Vascular/patología , Nicotina/toxicidad , Nifedipino/farmacología , Nifedipino/uso terapéutico , Nitrendipino/farmacología , Nitrendipino/uso terapéutico , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Ratas Sprague-Dawley , Factores de Riesgo , Verapamilo/farmacología , Verapamilo/uso terapéuticoRESUMEN
The effects of five different dietary levels of vitamin D3 on the coronary arteries of groups of 17-60 2-month old weanling Yorkshire swine were studied. Four groups were fed the following levels of vitamin D3 per ton of ration continuously for 4 months: group I--100,000 IU, group II--300,000 IU, group IV--2,000,000, and group V--4,000,000 IU. Swine in group III were fed the diet containing 100,000 IU of vitamin D3 per ton of ration for the first 2 months of the study after which they were fed a diet supplemented with 4,000,000 IU of vitamin D3 per ton of ration for the remaining 2 months of the study. The highest degree of intimal thickening of the coronary arteries was observed among group V. The thickened areas contained numerous lipid-containing cells and degenerate cells without stainable lipid. Electron microscopic examination revealed a greater frequency of degenerate cells without stainable lipid in the coronary arteries of groups III and IV than in groups I and II. These results suggest a possible link between excessive daily intake of vitamin D3 and the development of human coronary atherosclerosis.
Asunto(s)
Colecalciferol/toxicidad , Vasos Coronarios/efectos de los fármacos , Animales , Enfermedad Coronaria/inducido químicamente , Vasos Coronarios/ultraestructura , Humanos , Lípidos/sangre , Masculino , Microscopía Electrónica , Músculo Liso Vascular/efectos de los fármacos , PorcinosRESUMEN
Two experiments were conducted with 56-week-old or 104-week-old Leghorn hens to determine if feeding vitamin D steroids in excess of requirement levels caused any marked affects on eggshell quality. In the first experiment caged hens had reduced feed consumption, egg shell quality, and egg production as early as 6 weeks after initially consuming a basal diet supplemented with 6.8 micrograms 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3)/kg. The second experiment confirmed the previous results and showed that extensive weight loss occurred with continued feeding of 10 or 15 micrograms 1 alpha-OH-D3/kg diet. No adverse affects were observed in either experiment when the level of 1 alpha-OH-D3 supplementation was 5.0 micrograms/kg diet or less. No toxic effects were observed when the hormone precursor 25-OH-D3 was supplemented to diets at 6 or 12 micrograms/kg. It is suggested that the pathological effects observed are related to the potent calcium homeostatic properties of 1 alpha-OH-D3 that at elevated levels may cause aberrations in circulating calcium.
Asunto(s)
Calcifediol/toxicidad , Pollos/fisiología , Colecalciferol/toxicidad , Hidroxicolecalciferoles/toxicidad , Animales , Calcificación Fisiológica , Calcio/sangre , Cáscara de Huevo , Femenino , Aditivos Alimentarios , Oviposición , Fósforo/sangreRESUMEN
Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.