Assuntos
Aerossóis , Betametasona , Calcitriol , Fármacos Dermatológicos , Combinação de Medicamentos , Doenças da Unha , Psoríase , Humanos , Psoríase/tratamento farmacológico , Calcitriol/análogos & derivados , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Betametasona/administração & dosagem , Betametasona/análogos & derivados , Betametasona/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Doenças da Unha/tratamento farmacológico , Masculino , Feminino , Ureia/administração & dosagem , Ureia/uso terapêutico , Ureia/análogos & derivados , Adulto , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Postoperative hypocalcaemia is common after thyroidectomy. This study aimed to evaluate whether a standardised post-thyroidectomy protocol using prophylactic calcium and calcitriol reduces hypocalcaemia incidence after total thyroidectomy in children and adolescents. METHODS: A cohort children and adolescents ≤18 years of age undergoing total thyroidectomy between January 2016 and October 2022 in one institution were retrospectively identified and divided into pre-protocol and post-protocol groups. The primary outcome measure was hypocalcaemia (total serum calcium of <2.0 mmol/L; ionised serum calcium of 0.9 mmol/L). Secondary outcome measures were the occurrence of hypercalcaemia (serum Calcium >2.7 mmol/L; ionised calcium >1.31 mmol/L), length of hospitalisation and number of postoperative blood tests. RESULTS: There were 22 patients in each group (mean age 11.8; SD 4.3 years, female 36 %). The rate of hypocalcaemia was significantly higher in the pre-protocol group than the post-protocol group (54 % vs 13.6 %, p = 0.010). Patients in the pre-protocol group had more inpatient blood tests (mean 5.4; SD 3.2) than the post-protocol group (mean 3.3; SD 1.8, p = 0.011), although the total postoperative blood test count was similar between the groups. Six (13.6 %) patients developed hypercalcaemia. The rate of hypercalcaemia was similar between groups (pre-protocol 2, 9.1 %; post-protocol 4, 18.1 %; p = 0.664). Length of hospitalisation was similar between groups. CONCLUSION: Our standardized protocol decreased hypocalcemia and inpatient blood tests after total thyroidectomy in children. Future research should explore if incorporating preoperative calcium and calcitriol treatment, along with intraoperative PTH levels for risk management, can further reduce hypocalcemia rates in paediatric patients.
Assuntos
Calcitriol , Cálcio , Protocolos Clínicos , Hipocalcemia , Complicações Pós-Operatórias , Tireoidectomia , Humanos , Hipocalcemia/prevenção & controle , Hipocalcemia/etiologia , Hipocalcemia/epidemiologia , Hipocalcemia/sangue , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Feminino , Criança , Masculino , Adolescente , Estudos Retrospectivos , Cálcio/sangue , Calcitriol/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Hormônios e Agentes Reguladores de Cálcio/uso terapêuticoRESUMO
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.
Assuntos
Anticorpos Monoclonais Humanizados , Raquitismo Hipofosfatêmico Familiar , Fator de Crescimento de Fibroblastos 23 , Humanos , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento , Calcitriol/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Fósforo/sangueRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease. Vitamin D analogues are the first-line topical agents for the long-term management of psoriasis. Chinese herbal medicine (CHM) bath therapy is commonly employed for psoriasis. However, the effects and safety of CHM bath therapy for psoriasis vulgaris, using topical calcipotriol as the comparator, remain inconclusive. Furthermore, the combination of herbs, a distinctive feature of CHM, is essential for its therapeutic effects due to the individual and synergistic properties of the herbs involved. AIM OF THE STUDY: The review was conducted to evaluate the effectiveness and safety of CHM bath therapy for psoriasis vulgaris, using calcipotriol as the comparator. Potential herbs and herb combinations of CHM bath therapy were also explored for further drug discovery. MATERIALS AND METHODS: Nine databases were searched from inception until March 05, 2024. Randomised controlled trials (RCTs) investigating CHM bath therapy, using calcipotriol as the comparator, were included. Statistical analyses were performed using RevMan 5.4, Stata 12.0 and SPSS Clementine 12.0 software. The evidence certainty for outcomes was assessed using the approach proposed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group. Moreover, association rule analysis on herbs identified in the systematic review was conducted to explore the potential herbs and herb combinations. RESULTS: A total of 17 RCTs involving 1,379 participants were included in this systematic review. The findings of this review revealed that: 1) CHM bath therapy produced comparable effects to calcipotriol in reducing Psoriasis Area and Severity Index (PASI), Psoriasis Scalp Severity Index (PSSI), and itch visual analogue scale (VAS) at the end of the treatment phase; as well as exhibited a superior long-term effect than calcipotriol through decreasing relapse rates at the end of the follow-up phase; 2) CHM bath therapy showed an additional benefit when combined with calcipotriol in managing psoriasis vulgaris at the end of the treatment phase, in terms of PASI, PSSI, itch VAS, IL-17, IL-23, CD3+ and CD4+ T cells. The certainty of the evidence was rated as 'very low', 'low' or 'moderate' based on the GRADE assessment, considering some concerns or high risk of bias of included studies, substantial heterogeneity, and existing publication bias of some outcomes. Additionally, the proportions of participants reporting adverse events were similar in both groups. Association rule analysis of all included herbs identified 23 herb combinations including Prunus persica (L.) Batsch and Carthamus tinctorius L., as well as 11 frequently used herbs, such as Kochia scoparia (L.) Schrad., Dictamnus dasycarpus Turcz. And Sophora flavescens Ait. CONCLUSIONS: The effects of CHM bath therapy were comparable with those of topical calcipotriol but demonstrated a longer-lasting effect. Combining CHM bath therapy with calcipotriol also provided an additional benefit for adult psoriasis vulgaris. However, the certainty of the evidence was downgraded due to the methodological limitations of included studies. To confirm the findings of this review, future investigations should involve double-blinded, placebo-controlled RCTs. Importantly, it appears worthwhile to consider further research for drug development utilising the identified herbs or herb combinations.
Assuntos
Calcitriol , Fármacos Dermatológicos , Medicamentos de Ervas Chinesas , Psoríase , Humanos , Banhos , Calcitriol/análogos & derivados , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa/métodos , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Essential tremor (ET) is a neurological disease that impairs motor and cognitive functioning. A variant of the Lingo-1 genetic locus is associated with a heightened ET risk, and increased expression of cerebellar Lingo-1. Lingo-1 has been associated with neurodegenerative processes; however, neuroprotection from ET-associated degeneration can be conferred by the protein Sirt1. Sirt1 activity can be promoted by Resveratrol (Res) and 1,25-dihydroxyvitamin D3 (VitD3), and thus these factors may exert neuroprotective properties through a Sirt1 mechanism. As Res and VitD3 are linked to Sirt1, enhancing Sirt1 could counteract the negative effects of increased Lingo-1. Therefore, we hypothesized that a combination of Res-VitD3 in a harmaline injection model of ET would modulate Sirt1 and Lingo-1 levels. As expected, harmaline exposure (10 mg/kg/every other day; i.p.) impaired motor coordination, enhanced tremors, rearing, and cognitive dysfunction. When Res (5 mg/kg/day; i.p.) and VitD3 (0.1 mg/kg/day; i.p.) were given to adult rats (n = 8 per group) an hour before harmaline, tremor severity, rearing, and memory impairment were reduced. Individual treatment with Res and VitD3 decreased Lingo-1 gene expression levels in qPCR assays. Co-treatment with Res and VitD3 increased and decreased Sirt1 and Lingo-1 gene expression levels, respectively, and in some cases, beneficial effects on behavior were noted, which were not seen when Res or VitD3 were individually applied. Taken together, our study found that Res and VitD3 improved locomotor and cognitive deficits, modulated Sirt1 and Lingo-1. Therefore, we would recommend co-treatment of VitD3 and Res to leverage complementary effects for the management of ET symptoms.
Assuntos
Tremor Essencial , Harmalina , Resveratrol , Sirtuína 1 , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Sirtuína 1/metabolismo , Sirtuína 1/genética , Masculino , Ratos , Tremor Essencial/tratamento farmacológico , Tremor Essencial/metabolismo , Tremor Essencial/genética , Harmalina/farmacologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos , Ratos Sprague-Dawley , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
A 38-yr-old woman with chronic non-surgical hypoparathyroidism, managed elsewhere, presented to our practice with symptomatic hypocalcemia. At the age of 17, she began to suffer from muscle cramps, paresthesia, and ongoing diffuse pain. It took years before she was correctly diagnosed with hypoparathyroidism. Her symptoms were severe enough that she required emergency room visits several times a year. After she was properly diagnosed and started on calcium and calcitriol therapy, she continued to experience frequent episodes of severe hypocalcemia. She saw multiple healthcare providers who each introduced a new regimen. In addition, poor communication led to her discontinuing her medications altogether. As a result, her calcium levels remained consistently low, and she lost confidence in her prospect for better health. At the time of her visit to our clinic, she had discontinued calcitriol, was taking a large amount of oral calcium daily all at once, and had hypocalcemia. We addressed her concerns, and the challenges she faces with adherence to her medication regimen. We provided her with detailed information about the disease and the reasoning behind her treatment plan. Treatment was initiated with calcium carbonate 600 mg 3 times daily and calcitriol 0.5 mcg once daily. One week after treatment initiation, her test results showed improvement in her albumin-adjusted calcium, phosphorus, and 24-h urine calcium which were all within target range.
Assuntos
Hipoparatireoidismo , Humanos , Hipoparatireoidismo/tratamento farmacológico , Feminino , Adulto , Cálcio , Calcitriol/uso terapêutico , Hipocalcemia/tratamento farmacológicoRESUMO
BACKGROUND: Calcitriol has the potential to counteract fibrotic diseases beyond its classical action of maintaining calcium and bone metabolism; however, its functional mechanism remains unknown. Autophagy-related gene 16-like 1 (Atg16l1) is one of the genes related to autophagy and is involved in protecting against fibrotic diseases. The present study aimed to explore the contribution of autophagy to the inhibition of calcitriol-induced hepatic fibrosis, as well as its potential molecular mechanism. METHODS: Carbon tetrachloride (Ccl4)-treated mice were established as hepatic fibrosis models and received calcitriol treatment for 6 weeks. Quantification of Sirius red staining and measurement of key fibrotic markers (collagen-1 and α-SMA) was performed to detect hepatic fibrosis. Chloroquine (CQ) treatment was used to observe autophagic flux, and 3-methyladenine (3-MA) was used to inhibit autophagy. Furthermore, the effects of calcitriol on transforming growth factor ß1 (TGFß1)-stimulated primary hepatic stellate cells (HSCs) were detected. Downregulation of Atg16l1 or vitamin D receptor (VDR) in LX-2 cells was used to explore the mechanism of action of calcitriol in fibrosis and autophagy. Additionally, the electrophoretic mobility shift assay (EMSA) was used to investigate the interactions between VDR and ATG16L1. RESULTS: Calcitriol increased the expression of VDR and ATG16L1, enhanced autophagy and attenuated hepatic fibrosis. 3-MA treatment and VDR silencing abolished the protective effects of calcitriol against fibrosis. Calcitriol-induced anti-fibrosis effects were blocked by ATG16L1 suppression. Furthermore, VDR bound to the ATG16L1 promoter and downregulation of VDR decreased the expression of ATG16L1 in LX-2 cells. CONCLUSION: Calcitriol mitigates hepatic fibrosis partly through ATG16L1-mediated autophagy.
Assuntos
Proteínas Relacionadas à Autofagia , Autofagia , Calcitriol , Células Estreladas do Fígado , Cirrose Hepática , Receptores de Calcitriol , Animais , Humanos , Masculino , Camundongos , Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Tetracloreto de Carbono/toxicidade , Progressão da Doença , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos Endogâmicos C57BL , Receptores de Calcitriol/efeitos dos fármacos , Receptores de Calcitriol/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Pneumocystis jirovecii pneumonia (PJP) is a rare but serious complication of immunosuppression post-solid organ transplantation. We present a case of refractory, severe hypercalcaemia due to PJP in a renal transplant recipient. Treatment of PJP led to normalisation of the patient's calcium levels, and clinical improvement. To further explore the proposed calcitriol-driven mechanism leading to hypercalcaemia in PJP, we performed biochemical analysis on pre- and post-treatment serum and bronchoalveolar lavage sample at the time of PJP diagnosis. We confirmed high circulating and pulmonary levels of calcitriol in acute, untreated PJP with severe hypercalcaemia. PJP treatment led to reduction of circulating calcitriol to within normal range. We present this case, together with a literature review of similar reported cases, and the novel biochemical evidence supporting extra-renal production of calcitriol by activated pulmonary macrophages as the mechanism underpinning hypercalcaemia in PJP.
Assuntos
Hipercalcemia , Transplante de Rim , Pneumonia por Pneumocystis , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Transplante de Rim/efeitos adversos , Pneumonia por Pneumocystis/diagnóstico , Calcitriol/uso terapêutico , Hospedeiro ImunocomprometidoRESUMO
The definition of "Vitamin D" encompasses a group of fat-soluble steroid compounds of different origins with similar chemical structures and the same biological effects. Vitamin D deficiency and/or a defect in the process of its synthesis or transport predispose individuals to several types of rickets. In addition to cholecalciferol, ergocalciferol, and vitamins D3 and D2, there are also active metabolites for the treatment of this condition which are commercially available. Calcitriol and aphacalcidiol are active metabolites that do not require the renal activation step, which is required with calcifediol, or hepatic activation. The purpose of this review is to summarize current approaches to the treatment of rickets for generalist physicians, focusing on the best vitamin D form to be used in each type, or, in the case of X-linked hypophosphatemic rickets (XLH), on both conventional and innovative monoclonal antibody treatments.
Assuntos
Raquitismo Hipofosfatêmico Familiar , Raquitismo , Humanos , Vitamina D/uso terapêutico , Raquitismo/tratamento farmacológico , Raquitismo/metabolismo , Calcitriol/uso terapêutico , Colecalciferol/uso terapêutico , Colecalciferol/metabolismo , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/metabolismo , VitaminasRESUMO
OBJECTIVE: Vitamin D (a prohormone) is an important micronutrient required by the body for skeletal homeostasis and a range of non-skeletal actions. Calcitriol, the active form of vitamin D, regulates a variety of cellular and metabolic processes through both genomic and nongenomic pathways. Often prescribed for treating rickets and osteoporosis, vitamin D deficiency can exacerbate various other medical conditions. SIGNIFICANCE, METHODS, AND RESULTS: Despite its multifunctional uses, the sensitivity of vitamin D makes formulating an efficient drug delivery system a challenging task, which is further complicated by its poor aqueous solubility. Enhancing the oral absorption of vitamin D is vital in utilizing its full efficacy. Recent developments in encapsulation and nanotechnology have shown promising results in overcoming these constraints. CONCLUSION: This review thus offers an insight to adequately comprehend the mechanistic pharmacology of vitamin D, its pathophysiological role, and justification of its medical indications, along with the benefits of utilizing nanotechnology for vitamin D delivery.
Assuntos
Deficiência de Vitamina D , Vitamina D , Humanos , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Alimentos Fortificados , Calcitriol/fisiologia , Calcitriol/uso terapêutico , Vitaminas , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
INTRODUCTION: Vascular calcification is an intervenable factor in the pathophysiology of cardiovascular disease. Treatment-related factors might worsen the arterial stiffness in chronic hemodialysis patients. The aim of the study is to compare the effects of 1-year treatment with paricalcitol or calcitriol on pulse wave velocity (PWV), which is an indicator of arterial stiffness and osteocalcin and fetuin-A levels. METHODS: Seventy-six hemodialysis patients who had similar PWV1 at the beginning were evaluated after a 1-year treatment of paricalcitol or calcitriol. PWV2, serum osteocalcin, and fetuin-A levels were measured at the end of the study. RESULTS: At the end of the study, PWV2 of paricalcitol group was statistically lower than the calcitriol group. Osteocalcin levels were statistically lower and fetuin-A levels were statistically higher in the paricalcitol group than the calcitriol group at the end of the study. The number of patients with PWV2 > 7 m/s and using paricalcitol was 16 (39%) but 25 (41%) patients were using calcitriol; the differences were statistically significant. CONCLUSIONS: The long-term benefits of paricalcitol were superior to the benefits of calcitriol. Paricalcitol has protective effects from vascular calcification in chronic hemodialysis patients.
Assuntos
Calcitriol , Ergocalciferóis , Calcificação Vascular , Humanos , alfa-2-Glicoproteína-HS , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Osteocalcina , Hormônio Paratireóideo , Análise de Onda de Pulso , Diálise Renal/efeitos adversos , Calcificação Vascular/etiologiaRESUMO
The objective of this experiment was to determine the effect of intramammary calcitriol treatment on indicators of inflammation during an intramammary bacterial infection. Lactating Holstein cows were challenged with intramammary Streptococcus uberis. At the onset of mild or moderate mastitis, cows were randomly assigned to receive 10 µg of intramammary calcitriol (CAL, n = 7) or placebo control (CON; n = 6) after every milking for 5 days. Data were analyzed by ANOVA with mixed models using the MIXED procedure of SAS with significance declared at P ≤ 0.05. Milk somatic cells, mastitis severity scores, rectal temperatures, and milk bacterial counts did not differ between treatments. Calcitriol decreased the percentage of CD11b+CD14- cells in milk compared with CON (CON = 81 vs. CAL = 61 ± 5%). Antioxidant potential and concentrations of 15-F2t- isoprostanes in milk of infected quarters also were lower in CAL compared with CON. Transcripts for the 25-hydroxyvitamin D 24-hydroxylase and inducible nitric oxide synthase were greater in milk somatic cells of CAL compared with CON, but those for ß-defensin 7, metallothionein 1 A and 2 A, thioredoxin and thioredoxin reductase did not differ between treatments. Although clinical signs of severity did not differ, CAL influenced the composition of milk somatic cells and redox activity in milk of infected quarters.
Assuntos
Doenças dos Bovinos , Mastite Bovina , Feminino , Bovinos , Animais , Leite/microbiologia , Calcitriol/uso terapêutico , Calcitriol/farmacologia , Lactação , Oxirredução , Mastite Bovina/tratamento farmacológico , Mastite Bovina/microbiologia , Glândulas Mamárias Animais , Contagem de Células/veterináriaRESUMO
Patients with osteomalacia have a low bone mineral density (BMD) and are often misdiagnosed as osteoporosis. A marked increase in BMD is noticed following successful treatment of osteomalacia. The biochemical hallmark of tumour-induced osteomalacia (TIO) is hypophosphatemia. Patients with TIO often have severe hypophosphatemic osteomalacia and dual-energy X-ray absorptiometry may demonstrate low BMD. Surgical removal of the phosphatonin-secreting lesion restores serum phosphate, corrects osteomalacia and is associated with a dramatic increase in BMD. We report two patients with TIO and low BMD, who were treated with oral phosphate and calcitriol supplementation. The percentage increase in BMD at 33 months was as high as 94.3% in areas with the lowest BMD at baseline. The BMD at 33 months was higher than the +2SD of the population-specific reference ranges, a finding not reported in surgically treated patients with TIO. An intermittent rise in parathyroid hormone following oral phosphate supplementation might have resulted in such findings.
Assuntos
Hipofosfatemia , Osteomalacia , Humanos , Calcitriol/uso terapêutico , Fosfatos , Osteomalacia/complicações , Densidade Óssea , Hipofosfatemia/complicaçõesRESUMO
Previous studies noted an imbalance in T helper (Th) 17 and regulatory T cells (Tregs) in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis animal model. calcitriol, vitamin D's active form, was found to ameliorate EAE symptoms by favoring Tregss over Th17 cells, suggesting immunomodulatory effects. This study aimed to assess calcitriol's impact on EAE manifestations and cytokine profile in mice. In this study, we recruited twenty-eight C57BL/6 mice and divided them into 4 groups: healthy controls, EAE, EAE with calcitriol treatment, and healthy mice with calcitriol treatment. CD4+ T cells were isolated from splenocytes using magnetic-activated cell sorting. Real-time polymerase chain reaction was employed to quantify the genes associated with Th9 cells (i.e., SPI1 encoding PU.1 and IL9 encoding interleukin [IL]-9). Moreover, the levels of IL-17 and transforming growth factor beta (TGF-ß) were evaluated through enzyme-linked immunosorbent assay in the supernatant of CD4+ T cell culture stimulated by anti-CD3 and anti-CD28 antibodies for 72 hours. In the supernatant of CD4+ T cell cultures, the levels of interleukin-17 (IL-17) were significantly increased, while the levels of transforming growth factor beta (TGF-ß) were decreased in the EAE Group compared to the healthy control group. Calcitriol treatment reversed these changes and attenuated EAE symptoms, as confirmed in hematoxylin and eosin, and luxol fast blue stains. Notably, calcitriol increased IL9 gene expression in both EAE and healthy mice. This study provides further evidence of the anti-inflammatory effects of calcitriol and its role in attenuating EAE.
Assuntos
Encefalomielite Autoimune Experimental , Camundongos , Animais , Interleucina-9/metabolismo , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Interleucina-17/metabolismo , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta/genética , Células Th17RESUMO
Topical medications are commonly used to manage mild-to-moderate psoriasis and serve as adjunct therapies used in combination with phototherapy and systemic treatments. Fixed-dose calcipotriene (Cal) 0.005%/betamethasone dipropionate (BD) 0.064% aerosol foam is a safe, efficacious topical therapy approved for the treatment of psoriasis vulgaris in the United States and European Union. Several investigator-initiated studies (IISs) have been conducted to provide real-world evidence related to the safety, effectiveness, and therapeutic indications of Cal/BD foam and are relevant to clinicians' every-day practice. This paper summarizes the findings of the IISs around the globe published to date and presents the real-world data related to the effectiveness and clinical considerations of Cal/BD foam as a treatment for psoriasis. J Drugs Dermatol. 2023;22:9(Suppl 2):s5-14.
Assuntos
Calcitriol , Psoríase , Humanos , Aerossóis , Calcitriol/uso terapêutico , Psoríase/diagnóstico , Psoríase/tratamento farmacológicoRESUMO
Studies have shown that vitamin D plays a crucial role in brain development, brain metabolism and neuroprotection. There is little evidence for the neuroprotective effect of 1, 25dihydroxyvitamin D3 (1,25(OH)2D3) on various brain injury models. The aim of this study was to investigate the neuroprotection effect of 1,25(OH)2D3 against hyperoxiainduced brain injury in premature rats. SpragueDawley rats were exposed to 95% oxygen or room air for 24 h and treated with 1,25(OH)2D3 or normal saline for 14 consecutive days. The histopathological changes of optic chiasma tissue were observed by hematoxylineosin staining. Immunohistochemistry, qRTPCR, and western blot were performed to detect the expression of integrinß1 and yesassociated protein (YAP) in the organization of the optic chiasm. Histopathological sections of optic chiasma showed visible optic nerve swelling, expanded nerve fiber space, uneven staining, obvious oligodendrocyte proliferation and disordered cell arrangement accompanied by inflammatory cell infiltration and exudation after 7 days and 14 days of hyperoxia exposure. The hyperoxia group treated with 1,25(OH)2D3 were showed improvement of brain injury with reduced inflammatory exudation, uniform nerve fiber staining and less obvious oligodendrocyte proliferation. Immunohistochemical staining, qRTPCR and western blot indicated that 1,25(OH)2D3 treatment upregulated the expression of integrinß1 and YAP in the hyperoxia group on day 7. However, the expression of YAP was significantly increased compared with control group and treatment with 1,25(OH)2D3 reduced the expression of YAP in the hyperoxic group on day 14. 1,25(OH)2D3 may regulate the expression of integrinß1 and YAP to alleviate hyperoxiainduced brain injury in premature rats.
Assuntos
Lesões Encefálicas , Hiperóxia , Fármacos Neuroprotetores , Ratos , Animais , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Calcitriol/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Hiperóxia/complicações , Ratos Sprague-Dawley , Vitamina D/farmacologia , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , IntegrinasRESUMO
Calcipotriol (calcipotriene) is a synthetic vitamin D3 derivative that is a standard treatment option for psoriasis. It is generally well tolerated with minimal side effects. Due to its ability to reduce keratinocyte proliferation and induce keratinocyte differentiation as well as its immunomodulatory effects, calcipotriol has been used to treat a variety of skin disorders such as atopic dermatitis, actinic keratoses, lichen planus, seborrheic keratoses, and vitiligo [1]. We surveyed the literature examining the use of calcipotriol for non-psoriatic dermatologic disease.
Assuntos
Dermatite Atópica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Psoríase , Humanos , Calcitriol/uso terapêutico , Psoríase/tratamento farmacológicoRESUMO
Atopic dermatitis and psoriasis are prevalent chronic inflammatory skin diseases that are characterized by dysfunctional skin barriers and substantially impact patients' quality of life. Vitamin D3 regulates immune responses and keratinocyte differentiation and improves psoriasis symptoms; however, its effects on atopic dermatitis remain unclear. Here, we investigated the effects of calcitriol, an active form of vitamin D3, on an NC/Nga mouse model of atopic dermatitis. We observed that the topical application of calcitriol decreased the dermatitis scores and epidermal thickness of NC/Nga mice with atopic dermatitis compared to untreated mice. In addition, both stratum corneum barrier function as assessed by the measurement of transepidermal water loss and tight junction barrier function as evaluated by biotin tracer permeability assay were improved following calcitriol treatment. Moreover, calcitriol treatment reversed the decrease in the expression of skin barrier-related proteins and decreased the expression of inflammatory cytokines such as interleukin (IL)-13 and IL-33 in mice with atopic dermatitis. These findings suggest that the topical application of calcitriol might improve the symptoms of atopic dermatitis by repairing the dysfunctional epidermal and tight junction barriers. Our results suggest that calcitriol might be a viable therapeutic agent for the treatment of atopic dermatitis in addition to psoriasis.
Assuntos
Dermatite Atópica , Psoríase , Camundongos , Animais , Dermatite Atópica/metabolismo , Calcitriol/uso terapêutico , Colecalciferol/farmacologia , Qualidade de Vida , Pele/metabolismo , Citocinas/metabolismo , Interleucina-13/metabolismo , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Modelos Animais de DoençasRESUMO
Osteoarthritis (OA) is characterized by the lubrication dysfunction of a cartilage sliding interface caused by chronic joint inflammation, and effective nonsurgical therapy for advanced OA remains lacking. Addressing chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation simultaneously may hopefully tackle this challenge. Herein, we developed superlubricative zein@alginate/strontium@calcitriol (ZASC) nanospheres to treat advanced OA. ZASC was confirmed to significantly improve joint lubrication through traditional tribological tests and our proposed tribological experiment to mimic the intra-articular condition based on the human medial tibiofemoral joint tissues. This finding was attributed to the hydration lubrication formed around the alginate-strontium spheres that enabled ball-bearing lubrication and the filling of cartilage defects. Moreover, ZASCs that released calcitriol in a sustained manner showed proliferative, anti-inflammatory, and anti-apoptosis effects in vitro. Further experiments demonstrated that ZASC exerted chondroprotective effects by inhibiting the breakdown of the extracellular matrix in patient-derived OA cartilage explants. In vivo results demonstrated that ZASC can effectively maintain a normal gait to improve joint function, inhibit abnormal bone remodeling and cartilage degradation in early OA and can effectively reverse the advanced OA progression. Therefore, ZASC is a potentially nonsurgical therapeutic strategy for advanced OA treatments.