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ABSTRACT Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: −1.46, 95% confidence interval [CI]: −1.76 to −1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.
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Abstract Introduction: Hyperparathyroidism (SHPT) secondary to chronic kidney disease (CKD) is characterized by high levels of parathyroid hormone (PTH), hyperplasia of the parathyroid glands and cardiovascular disease. Selective and non-selective and selective vitamin D-receptor activators, calcimimetics, are available in the Brazilian market to reduce PTH levels. Objectives: To develop a cost-effectiveness (C/E) and budgetary impact (BI) analysis of intravenous paricalcitol vs. oral calcitriol for patients on dialysis with SHPT, from the perspective of the Brazilian Public Health Care System (SUS). Methodology: We built a decision-tree model to analyze C/E, which considered the outcome of avoided death and a time horizon of 1 year. As for the BI analysis, two scenarios were considered, one of demand and one of epidemiological approach, based on data from the Brazilian Society of Nephrology. Results: The analysis showed that the C/E ratio was R$ 1,213.68 per year, and an incremental effectiveness of 0.032, referring to avoided death. The incremental C/E ratio was R$37,927.50 per death averted by paricalcitol. It was estimated that the incremental BI with the expansion of paricalcitol use will be between R$1,600,202.28 and R$4,128,565.65 in the first year, considering the main and epidemiological scenarios. At the end of 5 years after the expansion of its use, an incremental BI was estimated between R$ 48,596,855.50 and R$ 62,90,555.73. Conclusion: Intravenous paricalcitol has superior efficacy and similar safety to oral calcitriol, reducing the overall mortality of dialysis patients, although it implies a higher cost.
Resumo Introdução: O hiperparatireoidismo secundário (HPTS) à doença crônica renal (DRC) é caracterizado por elevados níveis de paratormônio (PTH), hiperplasia das glândulas paratireoides e doença cardiovascular. Para a redução dos níveis do PTH, estão disponíveis no mercado brasileiro os ativadores não seletivos e seletivos do receptor da vitamina D e os calcimiméticos. Objetivos: Desenvolver análise de custo-efetividade (C/E) e de impacto orçamentário (IO) do paricalcitol intravenoso vs. calcitriol oral para pacientes em diálise com HPTS, na perspectiva do Sistema Único de Saúde. Metodologia: Foi construído um modelo de árvore de decisão para a análise de C/E, que considerou o desfecho morte evitada e um horizonte temporal de 1 ano. Quanto à análise de IO, foram considerados dois cenários, sendo um de demanda aferida e um de abordagem epidemiológica, baseado nos dados da Sociedade Brasileira de Nefrologia. Resultados: A análise mostrou que a relação de C/E foi de R$ 1.213,68 ao ano, e uma efetividade incremental de 0,032, referente à morte evitada. A razão de C/E incremental foi de R$ 37.927,50 por morte evitada para o paricalcitol. Estimou-se que o IO incremental com a ampliação do uso do paricalcitol estará entre R$ 1.600.202,28 e R$ 4.128.565,65 no primeiro ano, considerando os cenários principal e o epidemiológico. Já no fim de 5 anos após a ampliação do uso, estimou-se IO incremental entre R$ 48.596.855,50 e R$ 62.90.555,73. Conclusão: O paricalcitol intravenoso tem eficácia superior e segurança semelhante ao comparador calcitriol oral, diminuindo a mortalidade geral dos pacientes em diálise, embora implique maior custo.
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Objective:To observe the efficacy of calcitriol combined with calcium receptor agonist therapy in patients with chronic renal failure-secondary hyperparathyroidism (CRF-SHPT) and its serum β2-Effects of β2-microglobulin ( β2-MG) and fibroblast growth factor-23 (FGF-23) levels. Methods:A total of 86 patients with CRF-SHPT who were admitted to the Department of Nephrology, Huzhou Hospital of Traditional Chinese Medicine, Zhejiang University of Traditional Chinese Medicine from Mar. 2020 to Mar. 2022 were included. Triol treatment) , combined treatment group (43 cases, calcitriol + calcium receptor agonist treatment) , the treatment effect was evaluated, and the serum phosphorus (P 3-) , serum calcium (Ca 2+) , ,and serum levels were measured before and after treatment intact parathyroid hormone (iPTH) , β2-MG, FGF-23 and renal function, blood lipid index levels, the occurrence of adverse reactions during the administration period, the measurement data were compared between groups using independent samples t test, count Comparison of data between groups was performed using the χ2 test. Results:The total effective rate (90.70%) in the combined treatment group was significantly higher than that in the control group (72.09%) ( χ2=4.91, P=0.027) ; the levels of P 3- and iPTH in the combined treatment group after treatment [ (220.16±23.76) ng/L, (1.22±0.14) mmol/L] were significantly lower than the control group [ (301.25±31.71) ng/L, (1.64±0.18) mmol/L], and the Ca 2+ level in the combined treatment group was significantly higher (2.59±0.41) mmol/L. Compared with the control group (2.26±0.34) mmol/L ( t=13.42, 12.08, 4.06, P=0.000, 0.000, 0.0000) , the serum levels of β2-MG and FGF-23 in the combined treatment group after treatment [ (34.67±4.12) mg/L, (71.36±8.05) ng/L] were significantly lower than the control group [ (40.36±4.87) mg/L, (78.97±8.73) ng/L] ( t=5.85, 4.20, P=0.000, 0.000) ; After treatment, the levels of triglyceride (TG) and total cholesterol (TC) in the combined treatment group [ (1.51±0.19) mmol/L, (4.11±0.51) mmol/L] were significantly lower than those in the control group[ (1.74±0.24) mmol/L, (4.75±0.59) mmol/L] ( t=4.93, 5.38, P=0.000, 0.000) ; Serum creatinine (Scr) , blood urea nitrogen (blood urea) in the two groups after treatment. There was no significant change in nitrogen) levels ( P>0.05) ; there was no significant difference in the incidence of adverse reactions between the combined treatment group and the control group during the treatment period ( P>0.05) . Conclusion:The treatment of CRF-SHPT patients with calcitriol combined with calcium receptor agonists can effectively reduce the iPTH level, improve the calcium-phosphorus imbalance and lipid metabolism disorder, and down-regulate the serum FGF-23 and β2-MG levels without damaging renal function of the residual of the patients.
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Contexto: A suplementação de vitamina é considerada na prevenção de muitas doenças, incluindo a rinite alérgica, cuja prevalência tem aumentado nos últimos anos, impactando a saúde pública. Objetivo: Avaliar a efetividade da suplementação de vitamina D para a prevenção e o tratamento da rinite alérgica. Material e Métodos: Trata-se de sinopse baseada em evidências. Procedeu-se à busca por estudos que associavam a vitamina D à rinite alérgica em três bases eletrônicas de dados: Cochrane - Central de Registros de Ensaios Clínicos - CENTRAL (2022), PubMed (1966-2022) e Portal BVS (1982-2022) e no megabuscador de evidências TRIPDATABASE (2022). Dois pesquisadores independentemente extraíram os dados e avaliaram a qualidade dos estudos para a síntese. O desfecho primário de análise envolveu a redução de crises de rinite. Resultados: Foram encontrados 125 estudos. Cinco estudos (três ensaios clínicos randomizados e dois coortes) foram incluídos. Discussão: A literatura apresenta poucos estudos relacionando vitamina D e rinite alérgica. Os estudos em humanos são ensaios clínicos de baixa amostragem e elevada heterogeneidade, que avaliaram efetividade da suplementação de vitamina D para redução de sintomas da rinite. Os dois estudos coorte encontrados não estabeleceram relação entre a exposição à vitamina D e menor manifestação de doença alérgica. O nível de evidência é muito baixo e não permite, nesse momento, aferir a efetividade da vitamina D para essa finalidade. Conclusões: Não há evidência de efetividade da suplementação de vitamina D para tratamento e prevenção da rinite alérgica, sendo recomendada a realização de novos estudos de boa qualidade metodológica.
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Vitamine D , Calcitriol , Rhinite , Prévention des Maladies , Pratique factuelleRésumé
Objective:To investigate the effect and safety of calcitriol on high turnover osteodystrophy in the treatment of patients with maintenance hemodialysis renal failure.Methods:Eighty patients with maintenance hemodialysis renal failure from April 2018 to June 2020 were selected as study objects and divided into the control group (40 cases) and the observation group (40 cases) by the random number table method. The control group was treated with oral calcium carbonate and other oral calcium preparations. The observation group was additively treated with calcitriol on the basis of the control group for 3 months. The therapeutic efficacy and the incidence of adverse reactions during the treatment were compared between the two groups; the levels of bone metabolism related index, kidney function index, hematocrit (Hct) and hemoglobin (Hb) and other index were compared between the two groups before and after treatment.Results:The total effective rate of the observation group was higher than that of the control group: 95.0%(38/40) vs. 80.0%(32/40), the difference was statistically significant ( χ2 = 4.11, P<0.05). After treatment, the levels of immune reactivity parathyroid hormone (iPTH), serum phosphorus, bone alkaline phosphatase (BALP) in the observation group were lower than those in the control group: (391.74 ± 28.69) ng/L vs. (468.50 ± 30.52), (1.02 ± 0.16) mmol/L vs. (1.63 ± 0.21) mmol/L, (70.59 ± 4.15) U/L vs.(73.64 ± 4.09) U/L, and the level of serum calcium was higher than that in the control group: [(2.05 ± 0.13) mmol/L vs. (1.93 ± 0.11) mmol/L, the differences were statistically significant ( P<0.05). After the treatment, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum albumin (ALB) and the incidence of adverse reactions between the two groups had no significant differences ( P>0.05). Conclusions:The administration of calcitriol in the treatment of patients with maintenance hemodialysis renal failure can improve the status of high turnover osteodystrophy and anemia, and has a high safety.
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Introducción. La hipocalcemia es la complicación más frecuente de la tiroidectomía. La profilaxis con calcio/calcitriol es una alternativa costo-efectiva, sencilla y expedita para disminuir esta situación, sin alterar la función paratiroidea residual. Lo que no está claro es si hay superioridad de una dosis frente a otra, por lo que el objetivo de este estudio fue evaluar el comportamiento entre diferentes esquemas de profilaxis para hipocalcemia. Métodos. Estudio de cohorte retrospectivo de adultos operados en un hospital de cuarto nivel, entre febrero de 2017 y diciembre de 2020. Se calculó la tasa de síntomas, la hipocalcemia e hipercalcemia bioquímica en el control postquirúrgico durante las siguientes dos semanas. Se hizo análisis bivariado y multivariado entre dosis de calcio/calcitriol, otros factores asociados y los desenlaces mencionados. Resultados. Se incluyeron 967 pacientes. El 10 % presentaron síntomas. No hubo diferencias significativas en el calcio sérico del control posquirúrgico entre los grupos con distintas dosis de calcio. La dosis de carbonato de calcio >3600 mg/día y el calcio en las primeras 24 horas de cirugía se asociaron a la presencia de síntomas. La dosis de calcitriol <1 mcg/día y el bocio aumentaron el riesgo de hipocalcemia bioquímica, mientras que la dosis de 1,5 mcg/día lo disminuyó. Ninguna variable evaluada se asoció a hipercalcemia bioquímica. Conclusiones. Podemos establecer que dosis altas de carbonato de calcio no se asocian con menos hipocalcemia bioquímica, lo cual está a favor de usar dosis intermedias (3600 mg/día). De forma similar, la dosis de calcitriol de 1,5 mcg/día disminuye el riesgo de este desenlace. La identificación de variables que aumentan o disminuyen el riesgo de hipocalcemia posterior a tiroidectomía, como bocio o el nivel de calcio en las primeras 24 horas para este estudio, pueden determinar ajustes individuales en la dosis rutinaria profiláctica de calcio/calcitriol.
Introduction. Hypocalcemia is the most frequent complication of thyroidectomy. Calcium/calcitriol prophylaxis is a cost-effective, simple and expeditious alternative to reduce this situation, without altering residual parathyroid function. It is not clear whether there is superiority of one dose over another, so the objective of this study was to evaluate the behavior between prophylaxis doses for hypocalcemia. Methods. Retrospective cohort study of adults operated in a fourth level hospital, between February 2017 and December 2020. The rate of symptoms, biochemical hypocalcemia and hypercalcemia was calculated in the post-surgical control during the following two weeks. Bivariate and multivariate analyses were performed between calcium/calcitriol dose, other associated factors, and the mentioned outcomes. Results. Out of the 967 patients included, 10% presented symptoms. There were no significant differences in postoperative control serum calcium between the groups with different doses of calcium. The dose of calcium carbonate > 3600 mg/day and calcium in the first 24 hours of surgery were associated with the presence of symptoms. The dose of calcitriol <1 mcg/day and goiter increased the risk of biochemical hypocalcemia, while the dose of 1.5 mcg / day decreased it. No variable evaluated was associated with biochemical hypercalcemia. Conclusion. We can establish that high doses of calcium are not less associated with biochemical hypocalcemia, which is in favor of intermediate doses (i.e. 3600mg/day). In a similar way, the calcitriol dose of 1.5mcg/day decreases the risk of this outcome. The identification of variables that increase or decrease the risk of this complication (goiter or the 24h serum calcium in this study) can decide settings in the rutinary prophylactic dose of calcium/calcitriol.
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Humains , Complications postopératoires , Thyroïdectomie , Hypocalcémie , Calcitriol , Carbonate de calcium , HypercalcémieRésumé
@#Introduction: Myofibroblast formation in the interstitial area is the hallmark of chronic kidney disease (CKD). Endothelin signalling has been known to play role in physiology and pathophysiology in the kidney. Vitamin D has a reno-protective effect through inhibiting inflammation and fibrosis. However, the interaction between vitamin D and endothelin signalling in the CKD model has not been elucidated yet. Therefore, we aimed to check the difference impact of endothelin (ET) receptor in CKD. Methods: Sprague Dawley rats (3-months-old, 150-250grams) underwent 5/6 subtotal nephrectomy (SN) to induce CKD. Then, it was divided into 4 groups (each contains 6 rats): sham operation (SO), 5/6 subtotal nephrectomy (SN), calcitriol groups (0.01µg/100grBW/day (SN-D1), and 0.05µg/100grBW/day (SN-D2). Calcitriol was administered for 14 days after the surgery. The Sham Operation (SO) group was injected with NaCl. At the specified date, the rats were sacrificed and the kidneys were harvested. Fibrosis was quantified based on Sirius Red staining. Immunostaining was done for localizing fibroblast (PDGFRβ). The mRNA expressions of prepro-ET-1, endothelin receptor A (ETAR), endothelin receptor B (ETBR), and endothelial nitrite oxide synthase (eNOS) were quantified using reverse-transcriptase PCR (RT-PCR). Results: The CKD promotes an elevation of prepro-ET-1, ETBR, and eNOS, and reduction of ETAR (p<0.05) mRNA expression compared to the SO group. Administration of calcitriol (SN-D1 and SN-D2) showed the vice versa effects. However, only SN-D2 group consistently showed statistically significant differences whenever compared to either SO or SN groups. Conclusion: Calcitriol might attenuate interstitial fibrosis in CKD model via ET-1/eNOS signalling.
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Introducción: La pandemia del SARS-CoV-2 ha sido un desafío para la medicina en estos últimos años por su alta tasa de contagios y muertes asociadas. Progresivamente los investigadores han ido dilucidando vías de transmisión y manifestaciones clínicas más frecuentes, que han facilitado la detección el virus. Con el objetivo de optimizar la prevención y tratamiento en pacientes infectados, investigadores de todo el mundo han evaluado la importancia de la respuesta inmune frente al virus, destacando la acción de algunos inmunomoduladores, como por ejemplo, la vitamina D. Desarrollo: Tras invadir el organismo, el SARS-CoV-2 se une a receptores de las células epiteliales del tracto respiratorio, específicamente en el neumocito tipo II, disminuyendo la producción de surfactante y provocando una producción desregulada de citocinas proinflamatorias, principal responsable de los casos más severos. Se ha demostrado que la Vitamina D puede modular la respuesta inmune tras unirse a su receptor VDR, disminuyendo la liberación de citocinas proinflamatorias. Algunos estudios han determinado que el uso de suplementos de vitamina D en dosis altas pudieran producir efectos protectores frente a infecciones respiratorias agudas. Conclusión: Finalmente, pese a los estudios realizados que relacionan el déficit de vitamina D con casos más severos de COVID-19, aún se requiere más evidencia para recomendar suplementación.
Introduction: The SARS-CoV-2 pandemic has been a challenge for medicine in recent years, due to its high contagion rate and associated deaths. Researchers have progressively elucidated transmission methods and most frequent clinical manifestations, that helps the virus detection. With the objective of optimizing prevention and treatment of infected patients, researchers all over the world have evaluated the importance of the immune system response against the virus, highlighting some immunomodulators, such as vitamin D. Body: After SARS-CoV-2 invades the organism, it binds to the receptor located on the respiratory tract epithelial cells, specifically type 2 pneumocyte, decreasing surfactant production and increasing the production of pro inflammatory cytokines, being the main reason for severe cases. Vitamin D has been shown to modulate the immune response after binding to its receptor, decreasing the release of proinflammatory cytokines. Some studies have shown that vitamin D supplementation in high doses may produce protective effects against acute respiratory infections. Conclusion: Finally, even the studies that correlate vitamin D deficiency and COVID-19 severe cases, we still need more evidence to recommend Vitamin D supplementation.
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Humains , Vitamine D/génétique , Carence en vitamine D/complications , Carence en vitamine D/génétique , SARS-CoV-2/génétique , COVID-19/génétique , Vitamines , MortalitéRésumé
Abstract Background: At present, parathyroid hormone is the only existing anabolic bone therapy but produces hypercalcemia. Prostaglandin E1 (PGE1) has been suggested as a bone anabolic agent that allows bone modeling formation without producing hypercalcemia. This study aimed to corroborate these PGE1 properties. Methods: For 22 days, rabbits (n = 30) were divided into three groups (n = 10 each group) and received intravenous solutions: vehicle (control group), palate disjunction + vehicle (sham group), and palate disjunction + 50 mg of PGE1 (PGE1 group). On days 1, 3, and 22, palatine suture X-rays were taken. On day 22, bone formation markers were analyzed, and the rabbits were sacrificed. Bone palate undecalcified samples were processed. Histomorphometry software was used to analyze bone parameters, and the mineralization front was stained with toluidine blue. Scalloped lines reflect remodeling-based bone formation (RBF), and smooth lines reflect modeling-based formation (MBF). Results: X-rays showed more significant palatal disjunction in the PGE1 group; this group exhibited significant calcitriol serum increments. Hypercalciuria was observed in the PGE1 group, and resorption markers (N-telopeptides) remained stable. Sutural bones in the PGE1 group exhibited significant anabolism in structural parameters. RBF was 20%, and MBF was 6% in the sham group; in the PGE1 group, RBF was 8.6%, and MBF was 17%. In the PGE1 group, mineralization was significantly accelerated, but resorption remained stable. Conclusions: This model suggests that PGE1 favors palate disjunction, calcitriol synthesis, and shortens the mineralization. Therefore, PGE1 is an important bone anabolic molecule predominantly of modeling-based form and no hypercalcemia.
Resumen Introducción: La hormona paratiroidea es la única molécula anabólica ósea, pero ocasiona hipercalcemia. La prostaglandina E1 (PGE1) sugiere ser un anabólico óseo con formación por modelación predominante y generalmente no ocasiona hipercalcemia. El objetivo de este estudio fue corroborar estas propiedades de la PGE1. Métodos: Por 22 días, 30 conejos divididos en tres grupos (n = 10 cada grupo) recibieron una solución por vía intravenosa: vehículo (grupo control), disyunción palatina más vehículo (grupo sham) y disyunción palatina más 50 mg de PGE1 (grupo PGE1). A los días 1, 3 y 22 se obtuvieron radiografías de la sutura palatina. En el día 22 se analizaron los marcadores bioquímicos de formación ósea y se sacrificó a los conejos. Las suturas y los huesos suturales se procesaron sin descalcificar. La evaluación histomorfométrica fue digitalizada y el frente de mineralización ósea se tiñó con azul de toluidina. Las líneas irregulares reflejan resorción (remodelación) y las líneas rectas no resorción (modelación). Resultados: Radiográficamente, la disyunción palatina fue mayor en el grupo PGE1. Este grupo mostró una hipercalcitonemia significativa, pero la calcemia y los marcadores resortivos (N-telopéptidos) se mantuvieron estables. Por histomorfometría, los huesos suturales del grupo PGE1 mostraron anabolismo significativo en parámetros estructurales. En el grupo sham, la remodelación ósea fue del 20% y la modelación fue del 6%; en el grupo PGE1, la remodelación fue del 8.6% y la modelación fue del 17%. En este mismo grupo, la mineralización fue significativamente acelerada, pero la resorción se mantuvo igual. Conclusiones: Este modelo sugiere que la PGE1 favorece la disyunción palatina y el aumento del calcitriol, y acelera la mineralización y el anabolismo óseo por modelación predominante sin hipercalcemia.
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RESUMEN Objetivo: Describir la relación entre los niveles de 25-hidroxivitamina D y el riesgo cardiovascular en universitarios de Armenia- (Colombia). Materiales y métodos: Estudio descriptivo de corte transversal, durante 2017-2018. Se calculó el riesgo cardiovascular mediante las escalas Framingham, Framingham Colombia y OMS/ISH. Se determinaron los niveles de lípidos, insulina, citocinas y 25-hidroxivitamina D. Posteriormente se realizaron pruebas de Anova, regresión múltiple y prueba chi cuadrado. Se consideró un nivel de significancia cuando p<0,05. Resultados: La edad promedio fue 21,05 años (IC95: 20,62 - 21,48) y el promedio de vitamina D fue 27,7 ng/ml (IC95: 26,52 - 28,88). Hubo diferencias estadísticamente significativas por sexo (p=0,009), siendo más frecuente la deficiencia e insuficiencia en el sexo femenino. El promedio de Puntaje Framingham fue -4,02±3,7. La variación explicada (R2) del Puntaje Framingham tiene relación con colesterol (p<0,001), cHDL (p<0,001) y vitamina D (p=0,039). El Porcentaje Framingham se relaciona con edad (p=0,031), perímetro abdominal (p=0,005), interferón-y (p<0,001) e interleucina-6 (p=0,050). Conclusión: La deficiencia e insuficiencia de vitamina D fueron condiciones prevalentes en esta población. La variación explicada del modelo de puntaje Framingham se asoció con colesterol, cHDL y vitamina D. El porcentaje de Framingham tuvo relación con la edad, el perímetro abdominal, interferón-y e interleucina-6.
ABSTRACT Objective: To describe the correlation between 25-hydroxyvitamin D levels and cardiovascular risk in Armenia-Colombia. Materials and methods: During 2017-2018 was conducted a descriptive cross-sectional study. The cardiovascular risk was determined by Framingham, Framingham Colombia and OMS/ISH scores. Lipids, insulin, cytokines and 25-hydroxyvitamin D were measured. Then Anova test, multiple regression and Chi-square test were performed. Values below p<0.05 were considered statistically significant. Results: The average age was 21.05 years old (CI95: 20,62 - 21,48) and the average vitamin D levels was 27.7 ng/ml (CI95: 26,52 - 28,88). Statistically significant differences were also found by sex (p=0,009), deficiency and insufficient vitamin D were more frequent in women. The Framingham score was -4.02±3.7. There is a relation between the explained variation (R2) of the score with cholesterol (p<0.001), HDL cholesterol (p<0.001) and vitamin D (p=0.039). Framingham percentage is related to age (p=0.031), abdominal perimeter (p=0.005), interferon-Y (p<0.001) and interleukin-6 (p=0.050). Conclusion: Vitamin D deficiency and insufficiency were prevalent conditions. The explained variation of the Framingham score model is associated with cholesterol, HDL cholesterol and vitamin D. And the Framingham percentage with age, abdominal perimeter, interferon-Y and interleukin-6.
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Abstract Purpose To analyze the effect of calcitriol treatment on acute colitis in an experimental rat model. Methods A total of 24 adult Sprague Dawley albino rats were randomly separated into 3 equal groups: control group (n:8), colitis group (n:8), calcitriol administered group (n:8). A single dose of acetic acid (1 ml of 4% solution) was administered intrarectally to induce colitis. Group 1 was given 1 ml/kg 0.9% NaCl intraperitoneally; rats belonging to Group 2 were administered calcitriol 1 µg/kg for 5 days. Results Plasma tumor necrosis factor alpha, Pentraxin 3, and malondialdehyde levels were significantly lower in the calcitriol administered colitis group than in the standard colitis group (p<0.01). In the Calcitriol group, there was a significant histological improvement in hyperemia, hemorrhage and necrotic areas in the epithelium compared to the placebo group (p <0.000). Conclusion The findings suggest that calcitriol may be an agent that could be used in acute colitis treatment.
Sujets)
Animaux , Mâle , Calcitriol/usage thérapeutique , Colite/traitement médicamenteux , Anti-inflammatoires/usage thérapeutique , Valeurs de référence , Protéine C-réactive/analyse , Composant sérique amyloïde P/analyse , Peroxydation lipidique , Répartition aléatoire , Maladie aigüe , Reproductibilité des résultats , Facteur de nécrose tumorale alpha/analyse , Résultat thérapeutique , Rat Sprague-Dawley , Colite/sang , Colite/anatomopathologie , Stress oxydatif/génétique , Modèles animaux de maladie humaine , Malonaldéhyde/sangRésumé
Abstract Purpose: To evaluate protective effects of dexmedetomidine, calcitriol and their combination. Methods: Forty Wistar-albino rats were divided into 4 groups; group of Sham (Group Sham); group of dexmedetomidine (Group DEX); group of calcitriol (Group CAL) and group of dexmedetomidineandcalcitriol (Group DEX-CAL). Photographic analysis was used for macroscopic analysis and perfusion analyses were evaluated by scintigraphy. Additionally, tissue malondialdehyde (MDA) and total oxidant status (TOS) and total antioxidant activity (TAS) were recorded and oxidative stress index (OSI) was calculated. Each flap was assessed by histopathology. Results: Compared to Group Sham, the viable flap areas were higher in all treatment groups both by photographic image analyses and perfusion analyses (p<0.05). Group DEX-CAL had the highest viable flap percentage both in scintigraphic and photographic analyses; whereas Group Sham had the lowest viable flap percentage. Similarly, TAS and MDA levels were elevated and TOS levels were declined in all treatment groups compared to Group Sham (p<0.005). Histopathological analysis at flap demarcation zone confirmed neovascularization was significantly higher and edema, necrosis and inflammation were significantly lower in all treatment groups compared to Group Sham. Conclusion: The outcomes show that additional premedication with either dexmedetomidine or calcitriol or their combination reduces ischemia-reperfusion injury of flap area and show significant increase in the percentage of viable flap tissue.
Sujets)
Animaux , Rats , Lambeaux chirurgicaux , Calcitriol/pharmacologie , Lésion d'ischémie-reperfusion , Dexmédétomidine/pharmacologie , Rat WistarRésumé
ABSTRACT Vitamin D is a pleiotropic steroid hormone that modulates the autonomic balance. Its deficiency has been described as an environmental risk factor for multiple sclerosis (MS). The aim of this study was to investigate the serum levels of vitamin D, vitamin D binding protein (VDBP) and vitamin D receptors (VDR) and to evaluate cardiac dysautonomia in MS patients due to bidirectional interaction between vitamin D and the autonomic nervous system. Methods: The current cross-sectional study was conducted on 26 patients with relapsing-remitting MS and on 24 healthy controls. Twenty-four-hour ambulatory blood pressure variability (BPV) was calculated and the participants were evaluated for orthostatic hypotension and supine hypertension. Serum levels of vitamin D, VDBP and VDR were measured. Results: The mean serum vitamin D level was significantly lower in MS patients than in controls (p = 0.044); however there was no significant difference in terms of VDR and VDBP levels between the groups. Supine hypertension and orthostatic hypotension were significant and the 24-hour systolic BPV was significantly decreased in patients with MS (p < 0.05) compared to controls. No correlation was found between vitamin D, VDBP and VDR with supine hypertension, orthostatic hypotension and systolic BPV values (p > 0.05). Also, there was a negative correlation between VDBP and the EDSS (p = 0.039, r = −0.406). Conclusion: There was no correlation between orthostatic hypotension, supine hypertension and systolic BPV values and serum vitamin D, VDBP and VDR in MS patients. Future prospective studies with large number of patients may help us to better understand the relationship between vitamin D and the autonomic nervous system.
RESUMO A vitamina D é um hormônio esteroide pleiotrópico que modula o equilíbrio autonômico. Sua deficiência tem sido descrita como fator de risco ambiental para esclerose múltipla (EM). O objetivo deste estudo foi investigar os níveis séricos de vitamina D, proteína de ligação à vitamina D (VDBP) e receptor de vitamina D (VDR) e avaliar a disautonomia cardíaca em pacientes com EM devida à interação bidirecional entre vitamina D e sistema nervoso autônomo. Métodos: O presente estudo transversal foi realizado em 26 pacientes com EM remitente-recorrente e em 24 controles saudáveis. A variabilidade da pressão arterial ambulatorial (BPV) por 24 horas foi calculada e os participantes foram avaliados quanto à hipotensão ortostática e hipertensão supina. Os níveis séricos de vitamina D, VDBP e VDR foram medidos. Resultados: O nível sérico médio de vitamina D foi significativamente menor nos pacientes com EM do que nos controles (p = 0,044); no entanto, não houve diferença significativa em termos de níveis de VDR e VDBP entre os grupos. Hipertensão supina e hipotensão ortostática foram significativas e a BPV sistólica de 24 horas diminuiu significativamente em pacientes com EM (p < 0,05) em comparação aos controles. Não foi encontrada correlação entre vitamina D, VDBP e VDR com hipertensão supina, hipotensão ortostática e BPV sistólica (p > 0,05). Também houve correlação negativa entre VDBP e EDSS (p = 0,039, r = −0,406). Conclusão: Não houve correlação entre hipotensão ortostática, hipertensão supina e valores de BPV sistólica e vitamina D sérica, VDBP e VDR em pacientes com EM. Futuros estudos prospectivos com grande número de pacientes podem nos ajudar a entender melhor a relação entre vitamina D e sistema nervoso autônomo.
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Humains , Mâle , Femelle , Adolescent , Adulte , Adulte d'âge moyen , Jeune adulte , Maladies du système nerveux autonome/sang , Vitamine D/sang , Protéine de liaison à la vitamine D/sang , Récepteur calcitriol/sang , Sclérose en plaques récurrente-rémittente/sang , Dysautonomies primitives/sang , Valeurs de référence , Maladies du système nerveux autonome/physiopathologie , Carence en vitamine D/complications , Carence en vitamine D/sang , Pression sanguine/physiologie , Test ELISA , Études cas-témoins , Études transversales , Facteurs de risque , Décubitus dorsal/physiologie , Statistique non paramétrique , Sclérose en plaques récurrente-rémittente/physiopathologie , Dysautonomies primitives/étiologie , Dysautonomies primitives/physiopathologie , Rythme cardiaque/physiologie , Hypertension artérielle/physiopathologie , Hypertension artérielle/sang , Hypotension orthostatique/physiopathologie , Hypotension orthostatique/sangRésumé
Obesity is characterized by an abnormal production of adipocytokines, generating chronic inflammation associated in turn with endothelial dysfunction, atherosclerosis and insulin resistance. On the other hand, it is a risk factor for vitamin D deficiency, thus establishing an inverse relationship between the plasma levels of this nutrient and acute phase proteins with low vitamin D levels, being able to boost the inflammatory response in obesity. In this context, the correction of poor vitamin D status could be an effective addition to the treatment of obesity; however, evidence of future trials that can support the regulatory effects of supplementation is required. The objective of this review is to analyze the existing evidence and establish the relationship between plasma levels of vitamin D and chronic inflammation associated with obesity. The methodology consists of a sensitive search in the PubMed and Trip Database, limiting the search to articles in English and Spanish published through January 2019. Priority was given to clinical trials, original articles and systematic reviews, from which other relevant research was identified.
La obesidad se caracteriza por la producción anormal de adipocitocinas, generando inflamación crónica asociada a su vez a disfunción endotelial, aterosclerosis y resistencia a insulina. Por otra parte, es un factor de riesgo de déficit de vitamina D, estableciéndose una relación inversa entre los niveles plasmáticos de dicho nutriente y proteínas de fase aguda, pudiendo potenciar la respuesta inflamatoria en obesidad. En este contexto la corrección del mal estado de vitamina D podría ser una adición efectiva al tratamiento de la obesidad, sin embargo se requiere evidencia de futuros ensayos que se puedan respaldar los efectos reguladores de la suplementación. El objetivo de esta revisión es analizar la evidencia existente y establecer la relación entre los niveles plasmáticos de vitamina D y la inflamación crónica asociada con la obesidad. La metodología consiste en una búsqueda sensible en las bases de datos PubMed y Trip Database, limitándose la búsqueda a artículos en inglés y español hasta enero 2019. Se priorizó por ensayos clínicos, artículos originales y revisiones sistemáticas, a partir de los cuales se identificaron otras investigaciones relevantes.
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Humains , Carence en vitamine D , Inflammation , Obésité , AdipokinesRésumé
Background: Topical calcitriol and calcipotriol, the two vitamin D derivatives although considered efficient in treating psoriasis, their comparative studies are relatively scanty. The objective of the present study was to evaluate and compare the efficacy and safety of calcitriol and calcipotriol in stable chronic plaque-type psoriasis.Methods: Total 50 patients of chronic stable plaque-type psoriasis were randomly divided into two groups of 25 each. One group received calcitriol 3礸/g ointment and the other group received calcipotriol 50礸/g ointment twice daily for 12 weeks. Efficacy evaluations comprised global improvement (on a 4-point scale from 0: no change, to 3: clear or almost clear) assessed clinically and by the subject. Efficacy further included the 慸ermatological sum score� (DSS) at each study visit. Safety evaluations (on a 5-point scale from 0: none, to 4: very severe) included clinical assessment of cutaneous safety and assessment of cutaneous discomfort by the subject.Results: Both calcitriol and calcipotriol were significantly effective (p <0.001) in reduction of DSS but the difference between the two groups was not statistically significant. Mean score of global improvement assessed clinically was 2.20 for calcitriol and 2.16 for calcipotriol (p >0.05) and by the subject was 1.92 for calcitriol and 1.84 for calcipotriol (p >0.05). The difference between the two groups was not statistically significant. The mean worst score for cutaneous safety was higher in calcipotriol group compared to calcitriol group (0.28 vs 0.04 and 0.36 vs 0.04 by clinically and by the subject, respectively). Statistically significant better safety profile (p <0.05) was seen for calcitriol, only when assessed by the subject. 24% treatment related adverse events were reported with calcipotriol against only 4% with calcitriol.Conclusions: Topical calcitriol and calcipotriol showed similar efficacy in the treatment of chronic plaque psoriasis while calcitriol showed better safety profile in comparison with calcipotriol, in terms of local tolerance and induced less treatment related adverse events.
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Objective To investigate the clinical effect of oral calcitriol and calcium in the treatment of infantile rickets. Methods A total of 84 children with pediatric rickets treated in the department of pediatrics of our hospital from June 2017 to June 2018 were randomly divided into two groups. The control group received conventional oral vitamin D drops and calcium acetate. The observation group received oral calcitriol combined with calcium acetate. The clinical efficacy, blood biochemical changes, bone mineral density changes, height and body weight changes were compared between the two groups. Results The effective rate of the observation group was 97.62%, which was significantly higher than that of the control group (78.57%), and the difference was statistically significant (P<0.05). The blood calcium, blood phosphorus and 25-(OH) D3 in the observation group after treatment were significantly higher those in the control group.The BALP in the observation group was significantly lower than that of the control group, and the difference was statistically significant (P<0.05). The tibia, ulnar salt level and bone mineral density were significantly higher in the observation group than those in the control group (P<0.05). The height growth and body mass growth of the observation group after treat ment were significantly higher than those of the control group. The incidences of night terror, sweating, and baldness were significantly lower than those of the control group, and the difference was statistically significant (P<0.05).Conclusion Oral calcitriol and calcium are effective in treating children with rickets, which effectively improve blood calcium level and bone density, promote growth and development of children, reduce the incidence of clinical symptoms, and have positive clinical significance.
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Hypersensitivity to cholecalciferol (vitamin D3) or its active metabolite, calcitriol, is an exceedingly rare clinical phenomenon, with only 2 previously reported cases of suspected immediate hypersensitivity. Diagnosis of delayed drug hypersensitivity reactions is inherently difficult due to the lack of any robust in vitro diagnostic assay, particularly in those patients for whom provocation testing confers an unacceptable risk. In these situations, diagnosis relies on reproducible clinical manifestations following administration of the culprit agent, resolution upon its withdrawal and exclusion of other potential differential diagnoses. Based on these criteria, we propose the first reported case of delayed hypersensitivity to cholecalciferol successfully managed with a desensitisation protocol to pure cholecalciferol.
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Humains , Calcitriol , Cholécalciférol , Diagnostic , Diagnostic différentiel , Hypersensibilité médicamenteuse , Hypersensibilité , Hypersensibilité retardée , Hypersensibilité immédiate , Techniques in vitroRésumé
Aim: To observe the iconography and biomechanical changes of femur in this D-galactose induced osteoporosis model in male mice, using Micro CT and other methods, and to observe the effect of calcitriol in this model. Methods: Thirty SPF male KM mice of 17 weeks old were randomly divided into control group, model group and calcitriol group, and the drug administration lasted for 12 weeks. At the end of the experiment, the mice were sacrificed and the bilateral femurs were taken for a bio-mechanical three-point bending test and a Micro CT scan. Results: Compared with control group, the Micro CT index of the femur in model group showed that Conn. D., BMD, BV/TV and Tb. N were significantly reduced (P < 0. 05), and SMI was raised significantly (P < 0. 05). Compared with model group, the BMD, BV/TV, Tb. N and Tb. Th in calcitriol group were significantly raised (P <0. 05), and SMI was significantly reduced (P < 0. 05). What's more, the break load, elastic load, maximum load and stiffness coefficient in calcitriol group significantly increased (P < 0. 05). Conclusions: D-galactose can induce a visible iconography changes of osteoporosis in male mice. Calcitriol can significantly improve the micro structure of trabecular bone and increase the bio-mechanical properties of femur in D-galactose male mice.
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Objective To investigate the intervention effect of 1,25(OH)2D3 on serum level of parathyroid hormone,bone metabolic markers and muscle strength in the community elderly with low bone mass.Methods A total of 132 residents aged 60 years and over from Shanghai communities diagnosed as osteopenia or osteoporosis were enrolled and treated with 0.5 μg/d calcitriol for 3 months.Serum levels of parameters in blood biochemistry and bone metabolic markers were determined by Cobas Diagnosis System of Roche before and after treatment,and the handgrip strength of both left and right hands were measured at the same time.Results The average age of 132 patients was(66.1 ± 6.3) years,4 cases (all female) terminated their medication in advance,and 128 patients completed the treatment for three months.The baseline serum levels of 25 (OH)D and PTH were 19.6 ± 7.9 μg/L and 41.0 μg/L respectively.According to the median value of serum PTH before treatment,patients were divided into the two groups:the high PTH group and the low PTH group.Compared with the low PTH group,the serum levels of 25OHD and serum calcium were decreased in the high PTH group[(17.1 ± 7.0) μg/L vs.(22.1 ± 8.2) μg/L,2.4 mmol/L vs.2.5 mmol/L,P<0.05].After 3 months of intervention,serum levels of creatinine,urine calcium and left handgrip were significantly elevated[(68.2 ± 13.8) μmol/L vs.(65.2 ± 13.4) μmol/L,(5.9 ± 2.8)mmol/24 h vs.(4.4 ± 2.0) mmol/24 h,23.8 kg vs.21.0 kg,all P <0.05],while serum levels of PTH,eGFR,phosphorus were significantly decreased[35.5 ng/L vs.42.0 ng/L,(87.0 ± 17.0) ml/min vs.(93.1±17.9) ml/min,1.2 mmol/L vs.1.3 mmol/L,all P<0.05).There was a significant negative correlation between serum 25(OH)D and PTH before treatment(r=-0.312,P<0.05),but the negative correlation between them was no longer significant after 3 months of treatment (r =0.042,P > 0.05).A multivariate logistic regression analysis revealed that the increment of left handgrip strength greater than 25% (OR =0.138,95% CI:-0.002-8.383),the increment of serum calcium levels(OR =2.578,95%CI:1.0345-8.693)and age(OR =0.103,95%CI:0.035-0.345) were significantly correlated with the decrement of serum PTH levels greater than 30 % after three months of treatment.Conclusions Vitamin D diminution or deficiency is common in the elderly.The shortterm treatment of calcitriol can obviously reduce serum PTH,inhibit bone absorption and increase muscle strength.The effect of calcitriol on serum PTH is closely related to promoting calcium absorption and improving handgrip strength.
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Objective To investigate the differences in the expression of vitamin D receptor (VDR) and serum vitamin D levels in subcutaneous adipose tissue between overweight/obese and normal-weight gravidas, and the relationship between these two indicators and gestational diabetes mellitus (GDM). Methods Women with full-term singleton pregnancies who underwent elective cesarean section in Changzhou Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University from January 2015 to April 2017 were enrolled. Among them, there were 70 cases GDM women, including 35 normal-weight (NW-GDM group) and 35 overweight/obese women (OW-GDM group). During the same period, another 70 pregnant women with normal glucose tolerance who underwent scheduled cesarean delivery were selected as the control group, including 35 normal weight women (NW-control group) and 35 obese/overweight women (OW-control group). Fasting blood samples were collected before operation to determine the levels of different biomarkers, including vitamin D, lipid, fasting blood glucose, fasting insulin and adiponectin, and to calculate the homeostasis model assessment-insulin resistance (HOMA-IR). Two subcutaneous adipose tissue samples of the abdominal wall were taken during the operation to detect the expression and distribution of VDR protein with immunohistochemistry. Meanwhile, VDR mRNA transcription level was quantitatively analyzed using real-time fluorescence quantitative polymerase chain reaction. One-way analysis of variance, LSD, Kruskal-Wallis test, Mann-Whitney U test, Chi-square test and logistic regression analysis were used for statistical analysis. ResuLts (1) The body mass index (BMI) of the OW-control group and the OW-GDM group before pregnancy and delivery were all higher than that of the NW-control group and the NW-GDM group [BMI before pregnancy: (29.2±2.9), (29.4±3.8) vs (21.1±2.3) and (21.9±2.0) kg/m2, F=87.766; BMI before delivery: (35.2±3.4), (35.1±4.3) vs (27.9±2.8) and (28.8± 3.3) kg/m2, F=44.827; all P<0.001]. Newborn birth weight and the proportion of diabetic family history in the OW-GDM group were higher comparing to the NW- and OW- control group [(3 893±498) vs (3 501±402) and (3 625±332) g, F=4.751; 22.9%(8/35) vs 5.7%(2/35) and 5.7%(2/35), χ2=7.869; all P<0.05]. (2) In the OW-control group, the fasting insulin level and HOMA-IR were higher and the adiponectin and vitamin D concentration were lower than those in the NW-control group [13.3(12.3-14.5) vs 12.0(10.4-13.3) mmol/L, 2.7(2.4-3.0) vs 2.2(2.0-2.7), (61.8±20.4) vs (74.9±29.3) ng/ml, (21.6±7.2) vs (25.9±7.3) ng/ml; all P<0.05], and similar results were found between the OW-GDM group and the NW-GDM group [15.3(12.3-19.5) vs 12.0(10.1-15.8) mmol/L, 3.4(2.6-4.1) vs 2.6(2.1-3.2), (50.3±22.3) vs (62.1±23.2) ng/ml, (17.1±6.7) vs (20.6±7.9) ng/ml, all P<0.05]. Compared with the NW-control group, the NW-GDM group had higher fasting glucose and lower high density lipoprotein-cholesterol (HDL-C), adiponectin and vitamin D levels [4.6(4.3-5.1) vs 4.3(4.0-4.5) mmol/L, 1.7(1.6-1.9) vs 2.1(1.6~2.4) mmol/L, (62.1±23.2) vs (74.9±29.3) ng/ml, (20.6±7.9) vs (25.9±7.3) ng/ml; all P<0.05]. Compared with the OW-control group, fasting glucose, fasting insulin and HOMA-IR were higher and HDL-C, adiponectin and vitamin D levels were lower in the OW-GDM group [4.7(4.4-5.4) vs 4.5(4.2-4.7) mmol/L, 15.3(12.3-19.5) vs 13.3(12.3-14.5) mmol/L, 3.4(2.6-4.1) vs 2.7(2.4-3.0), 1.6(1.4-1.8) vs 1.9(1.7-2.2) mmol/L, (50.3±22.3) vs (61.8±20.4) ng/ml, (17.1±6.7) vs (21.6±7.2) ng/ml; all P<0.05]. (3)The overall vitamin D deficiency rate during the third trimester of the four groups was 78.6% (110/140), and the figure was 62.8% (22/35), 82.8% (29/35), 77.1% (27/35) and 91.4% (32/35) in the NW-control group, OW-control group, NW-GDM group and OW-GDM group (χ2=8.994, P=0.029), indicating a higher rate in the OW-GDM group than that in the NW-control group (χ2=8.102, P=0.004). (4) VDR was expressed in the nucleus of adipose tissue in all samples and statistic difference in protein expression was found among the four groups. VDR mRNA expression was higher in both GDM subgroups than that in the two control subgroups, and also higher in the two overweight/obese subgroups than in the corresponding normal-weight subgroups. (5)Serum vitamin D level was negatively correlated with fasting blood glucose and pre-pregnancy BMI, and positively correlated with adiponectin (P<0.05). The incidence of GDM was related to family history of diabetes, VDR mRNA, total cholesterol, HDL-C and HOMA-IR. ConcLusions GDM and overweight/obese patients had decreased serum vitamin D level and increased VDR in subcutaneous adipose tissue. These two factors are closely related to GDM.