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1.
Brasília; CONITEC; nov. 2020.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1141492

RESUMEN

CONTEXTO: Os distúrbios do metabolismo mineral e ósseo (DMO) que ocorrem na doença renal crônica (DRC) são frequentes e caracterizam-se pela presença de alterações dos níveis séricos de cálcio, fósforo, vitamina D e hormônio da paratireoide (PTH), de anormalidades ósseas (remodelação, mineralização e volume ósseo) ou da presença de calcificações extraesqueléticas. Dentre estes, a deficiência de calcitriol é um importante mecanismo envolvido na progressão do hiperparatireoidismo secundário (HPTS). Estas anormalidades da DRC podem contribuir para o desenvolvimento de doença cardiovascular, calcificação vascular e mortalidade. Segundo censo de 2015 da Sociedade Brasileira de Nefrologia, estima-se que 111.303 pacientes se encontram em terapia renal substitutiva, sendo que aproximadamente 90% estão em hemodiálise. Destes, aproximadamente 33% apresentavam hiperfosfatemia, 18% níveis de PTH acima de 600 pg/mL e 14% abaixo de 100 pg/mL. Em relação ao tratamento, cerca de 11% usavam calcitriol, 3% paricalcitol e 3% cinacalcete. Dentre as opções terapêuticas preconizadas pelo Protocolo Clínico e Diretrizes Terapêuticas (PCDT) do Distúrbio Mineral Ósseo na Doença Renal Crônica, do Ministério da Saúde, está o calcitriol, em cápsulas de 0,25 mcg e ampolas de 1 mcg para uso intravenoso. Segundo o PCDT, as doses orais e injetáveis de calcitriol são equivalentes. Portanto cada ampola de calcitriol de 1 mcg equivale a 4 comprimidos de calcitriol 0,25 mcg. TECNOLOGIA: calcitriol 1,0 mcg/mL injetável. JUSTIFICATIVA DA EXCLUSÃO: Atualmente, há apenas um registro sanitário válido para o calcitriol 1,0 mcg/mL injetável no Brasil. Entretanto, sua única empresa fabricante, Abbvie Farmacêutica Ltda., informou ao DAF sua decisão de descontinuar a comercialização do medicamento no país, de modo que calcitriol 1,0 mcg/mL injetável só deve ser comercializado até o fim do ano de 2020. Tendo isso em mente e considerando que existem outros medicamentos preconizados pelo referido PCDT, incluindo o calcitriol 0,25 mcg em cápsula, o DAF entende que a população não deixará de ser atendida devido à ausência de alternativas terapêuticas para essa condição. Além disso, o PCDT do Distúrbio Mineral Ósseo na DRC considera que ambas as apresentações farmacêuticas são equivalentes. Dessa forma, a exclusão de calcitriol 1,0 mcg/mL injetável do SUS se faz necessária para que os pacientes que atualmente o utilizam possam migrar para as demais terapias disponíveis, sem que haja interrupções em seus tratamentos. RECOMENDAÇÃO FINAL DA CONITEC: O Plenário da Conitec, em sua 92ª Reunião Ordinária, no dia 04 de novembro de 2020, deliberou por unanimidade recomendar a exclusão do calcitriol 1,0 mcg/mL injetável, no SUS. Assim, foi assinado o Registro de Deliberação nº 571/2020. DECISÃO: Excluir o medicamento calcitriol 1,0 mcg/mL injetável, no âmbito do Sistema Único de Saúde ­ SUS, conforme Portaria nº 57, publicada no Diário Oficial da União nº 228, seção 1, página 716, em 1º de dezembro de 2020.


Asunto(s)
Humanos , Calcitriol/uso terapéutico , Recall de Medicamento/organización & administración , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio , Inyecciones Intravenosas
2.
G Ital Nefrol ; 37(5)2020 Oct 05.
Artículo en Italiano | MEDLINE | ID: mdl-33026203

RESUMEN

We report the case of a 93-year-old woman on haemodialysis treatment for more than 30 months and with multiple comorbidities who recovered from a Covid-19 infection without any significant clinical problems. The patient has shown a delay in viral clearance with swab test negativization (confirmed) after 33 days; after testing positive again, she has resulted persistently negative, (confirmed after 49 days). After the first negative swab, IgG and IgM antibodies have been found; these have remained persistently positive after a month. As well as highlighting an unexpected resilience in an extremely fragile context, the analysis of this case draws attention to patients' management and, potentially, to the need to arrange dialysis treatments in isolation for some time after their "laboratory recovery".


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Pandemias , Neumonía Viral/complicaciones , Diálisis Renal , Sobrevivientes , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , Calcitriol/uso terapéutico , Técnicas de Laboratorio Clínico , Comorbilidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Heparina/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Nasofaringe/virología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Factores de Tiempo
3.
Restor Neurol Neurosci ; 38(4): 343-354, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32597823

RESUMEN

Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a "Systemic AhR Activation Syndrome" (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/fisiopatología , Indolamina-Pirrol 2,3,-Dioxigenasa/fisiología , Pandemias , Neumonía Viral/fisiopatología , Receptores de Hidrocarburo de Aril/fisiología , Contaminantes Atmosféricos/efectos adversos , Calcitriol/uso terapéutico , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/tratamiento farmacológico , Dexametasona/uso terapéutico , Ejercicio Físico , Retroalimentación Fisiológica , Femenino , Fibrosis/etiología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/biosíntesis , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Inflamación/etiología , Quinurenina/fisiología , Masculino , Terapia Molecular Dirigida , Insuficiencia Multiorgánica/etiología , Trabajo de Parto Prematuro/etiología , Neumonía Viral/complicaciones , Neumonía Viral/tratamiento farmacológico , Embarazo , Complicaciones Infecciosas del Embarazo/fisiopatología , Receptores de Hidrocarburo de Aril/biosíntesis , Receptores de Hidrocarburo de Aril/genética , Trastornos de la Sensación/etiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Tromboembolia/etiología , Tocoferoles/uso terapéutico
4.
Acta Cir Bras ; 35(4): e202000404, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32555936

RESUMEN

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.


Asunto(s)
Antiinflamatorios/uso terapéutico , Calcitriol/uso terapéutico , Colitis/tratamiento farmacológico , Enfermedad Aguda , Animales , Proteína C-Reactiva/análisis , Colitis/sangre , Colitis/patología , Modelos Animales de Enfermedad , Peroxidación de Lípido , Masculino , Malondialdehído/sangre , Estrés Oxidativo/genética , Distribución Aleatoria , Ratas Sprague-Dawley , Valores de Referencia , Reproducibilidad de los Resultados , Componente Amiloide P Sérico/análisis , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisis
5.
Medicina (B Aires) ; 80(3): 289-291, 2020.
Artículo en Español | MEDLINE | ID: mdl-32442945

RESUMEN

Hypoparathyroidism (HypoPT) is a rare disease characterized by low calcium and inappropriately low circulating parathormone levels. We present the case of a 25-year-old high-performance athlete male, with history of HypoPT after total thyroidectomy for papillary thyroid carcinoma (T3 N1b M0) two years before, who was referred to our clinic for symptomatic hypocalcemia. The patient reported serum calcium average levels of 7mg%, presented symptoms of hypocalcemia at rest and had multiple hospital admissions. First, standard treatment was optimized by calcium supplementation up to 12g/d and active vitamin D, not showing clinical or biochemical improvement. Malabsorption and complications of chronic HypoPT were ruled out. The 36-Item Short Form Health Survey (SF-36) demonstrated an impaired quality of life (QoL). Full-length recombinant human parathyroid hormone [rhPTH(1-84)] therapy was started with 50υg/d subcutaneous, and later adjusted to 75υg/d and the oral treatment gradually decreased. Currently, he is asymptomatic, with serum calcium levels above 9mg%, without receiving oral medication. He performs sports activity and shows marked improvement in quality of life according to SF-36 questionnaire.


Asunto(s)
Hipoparatiroidismo/tratamiento farmacológico , Hormona Paratiroidea/uso terapéutico , Adulto , Calcitriol/uso terapéutico , Hormonas y Agentes Reguladores de Calcio/uso terapéutico , Terapia de Reemplazo de Hormonas/métodos , Humanos , Hipoparatiroidismo/etiología , Masculino , Cáncer Papilar Tiroideo/complicaciones , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/cirugía , Tiroidectomía/efectos adversos , Vitamina D/uso terapéutico
7.
J Steroid Biochem Mol Biol ; 201: 105696, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32407869

RESUMEN

Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. However, no drugs can regenerate lung tissue in COPD patients, and differentiation-inducing drugs that can effectively treat damaged alveoli are needed. In addition, the presence of systemic comorbidities is also considered problematic. Our previous study revealed that a retinoic acid derivative improved emphysema in elastase-induced COPD model mice at a dose of 1.0 mg/kg, whereas 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) showed an emphysema-improving effect in the same model at 0.1 µg/kg. Elastase-induced COPD model mice do not exhibit a systemic disease state, so evaluation in a model that better reflects the human disease state is considered necessary. To solve this problem, we focused on the adiponectin-deficient mouse and examined the effects of 1,25(OH)2D3 on alveolar regeneration. Fifty-week-old adiponectin-deficient mice were treated with 1,25(OH)2D3 (0.1 µg/kg) twice a week, for 30 weeks. The effects of pulmonary administration on alveolar repair were evaluated according to the distance between alveolar walls (Lm values) and computed tomography (CT) parameters. Bone density was evaluated based on CT. The administration of 1,25(OH)2D3 was confirmed to show a significant therapeutic effect. The Lm values in the control and 1,25(OH)2D3-treated groups were 98 ± 4 µm and 63 ± 1 µm, respectively. However, on CT, the average CT value and % of low attenuation area showed no significant change. In adiponectin-deficient mice, the reduction of bone density (cortical, spongy, and total bone), which is a systemic symptom of COPD, was significantly suppressed by 1,25(OH)2D3 at 80 weeks of age. The present study suggests that 1,25(OH)2D3 could be a potential candidate drug that may provide a radical cure for the lung disease and comorbidities of COPD patients. This work can lead to the development drugs that may provide a radical cure for COPD.


Asunto(s)
Calcitriol/uso terapéutico , Enfisema/tratamiento farmacológico , Alveolos Pulmonares/efectos de los fármacos , Adiponectina/genética , Animales , Densidad Ósea/efectos de los fármacos , Calcitriol/farmacología , Enfisema/diagnóstico por imagen , Enfisema/patología , Masculino , Ratones Transgénicos , Alveolos Pulmonares/diagnóstico por imagen , Alveolos Pulmonares/patología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Tomografía Computarizada por Rayos X
8.
J Leukoc Biol ; 108(1): 283-295, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32237257

RESUMEN

1,25-dihydroxyvitamin D3 (1,25(OH)2 D3, VitD3) is the major active ingredient of vitamin D and has anti-inflammatory activity; however, the mechanism for this remains poorly understood. In this study, we found that VitD3 was able to abolish NOD-like receptor protein 3 (NLRP3) inflammasome activation and subsequently inhibit caspase-1 activation and IL-1ß secretion via the vitamin D receptor (VDR). Furthermore, VitD3 specifically prevented NLRP3-mediated apoptosis-associated speck-like protein with a caspase-recruitment domain (ASC) oligomerization. In additional to this, NLRP3 binding to NIMA-related kinase 7 (NEK7) was also inhibited. Notably, VitD3 inhibited autophagy, leading to the inhibition of the NLRP3 inflammasome. Uncoupling protein 2-reactive oxygen species signaling may be involved in inflammasome suppression by VitD3. Importantly, VitD3 had both preventive and therapeutic effects on mouse model of ulcerative colitis, via inhibition of NLRP3 inflammasome activation. Our results reveal a mechanism through which VitD3 represses inflammation and prevents the relevant diseases, and suggest a potential clinical use of VitD3 in autoimmune syndromes or other NLRP3 inflammasome-driven inflammatory diseases.


Asunto(s)
Calcitriol/uso terapéutico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Autofagia/efectos de los fármacos , Proteínas Adaptadoras de Señalización CARD/metabolismo , Calcitriol/farmacología , Caspasa 1/metabolismo , Polaridad Celular/efectos de los fármacos , Colitis Ulcerosa/enzimología , Colitis Ulcerosa/inmunología , Colon/efectos de los fármacos , Colon/patología , Sulfato de Dextran , Activación Enzimática/efectos de los fármacos , Interleucina-1beta/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/enzimología , Macrófagos Peritoneales/patología , Ratones , Quinasas Relacionadas con NIMA/metabolismo , Proteolisis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Receptores de Calcitriol/metabolismo , Transducción de Señal/efectos de los fármacos , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Ubiquitinación/efectos de los fármacos , Proteína Desacopladora 2/metabolismo
9.
Actual. osteol ; 16(1): 12-25, Ene - abr. 2020. ilus, graf, tab
Artículo en Español | LILACS | ID: biblio-1130045

RESUMEN

La paratiroidectomía (PTX) es la terapia de elección en el hiperparatiroidismo secundario a enfermedad renal crónica (HPT-ERC) resistente al tratamiento médico. El objetivo del presente estudio fue evaluar el resultado de la PTX a largo plazo y sus factores predictores. Métodos: estudio unicéntrico retrospectivo observacional. Se incluyeron 92 pacientes con HPT-ERC en diálisis, en quienes se realizó la primera PTX en el Hospital Italiano de Buenos Aires entre 2006 y 2015 con seguimiento ≥ 6 meses. Se consideró persistencia del HPTERC con PTH > 300 pg/ml en el semestre posoperatorio, y recidiva con PTH > 500 pg/ml luego. Resultados: edad: 43,6±12,8 años, 50% mujeres, mediana 4,6 años de diálisis, PTH preoperatoria mediana 1639 pg/ml. A 39 se les realizó PTX subtotal (PTXS) y a 53 total con autoimplante (PTXT+AI). Se observó persistencia en 16 pacientes (17,4%). Presentaron recidiva 30 de 76 pacientes con adecuada respuesta inicial (39,5%; IC 95 28,5-50,5). La mediana de tiempo hasta la recidiva fue de 4,7 años (RIC 2,3-7,5). Los pacientes con recidiva presentaron mayor calcemia preoperatoria (mediana 9,9 vs. 9,3 mg/dl, p=0,035; OR ajustado 2,79) y menor elevación de fosfatasa alcalina en el posoperatorio (333 vs. 436 UI/l, p=0,031; OR ajustado 0,99). La recidiva se presentó más frecuentemente luego de la PTXT+AI (48,9%; OR ajustado 4,66), que en la PTXS (25,8%). Conclusiones: el tiempo en diálisis con inadecuado control metabólico constituye el principal factor para la recurrencia del HPT. Se postula que la mayor calcemia preoperatoria está relacionada con un HPT más severo y se asocia a recurrencia. Llamativamente, hallamos menores elevaciones de la fosfatasa alcalina durante el posoperatorio en pacientes con recurrencia. Hipotetizamos que esto pueda asociarse con menor mineralización en el posoperatorio e hiperfosfatemia sostenida, con consecuente estímulo paratiroideo. La menor recurrencia del HPT luego de la PTXS se vincula al sesgo generado en la selección del tipo de cirugía. (AU)


Parathyroidectomy is an effective therapy for refractory secondary hyperparathyroidism (sHPT). Continued dialysis represents risk for recurrent sHPT. The aim of this study was to estimate the proportion of recurrence and determine its predictors. Methods: We conducted a retrospective observational study of 92 adults in chronic dialysis, who underwent their first parathyroidectomy in this center between 2006 and 2015. We considered persistence of sHPT if PTH was > 300 pg/ml during the first postoperative semester, and recurrence if it was > 500 pg/ml afterwards. Results: Age 43.6+-12 y/o, 50% female, 4.6 years on dialysis, median preoperative PTH 1636 pg/ml (IQR 1226-2098). Subtotal parathyroidectomy (sPTX) was performed in 39, Total with autotransplantation (TA-PTX) in 53 patients. Persistence of sHPT occurred in 16 patients; relapse in 30 out of 76 with adequate initially response (39.5%; 95CI 28,5-50,5). Median time to recurrence: 4.7 y. Recurring patients had higher preoperative calcemia (9.9 vs 9.3 mg/dl; adj OR 2.79) and lower postoperative elevation of ALP (333 vs 436 UI/ml; adj OR 0.99). Recurrence presented more frequently in TA-PTX (48.9%; adj OR 4.66) than sPTX (25.8%). Conclusions: Time on dialysis with inadequate metabolic control remains the most important risk factor for sHPT recurrence. Higher preoperative levels of calcemia, related to sHPT severity, are associated with recurrence. Lower elevations of ALP during postoperative period in recurring patients are an interesting finding. We hypothesize that patients with less significant postoperative mineralization may have chronically higher levels of phosphatemia, stimulating parathyroid glands. Fewer recurrence in sPTX is associated to a bias in the procedure selection. (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Paratiroidectomía/estadística & datos numéricos , Hiperparatiroidismo Secundario/complicaciones , Recurrencia , Vitamina D/uso terapéutico , Calcitriol/análogos & derivados , Calcitriol/uso terapéutico , Calcio/sangre , Estudios Retrospectivos , Diálisis Renal , Fosfatasa Alcalina/sangre , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/terapia , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/diagnóstico , Hiperparatiroidismo Secundario/terapia
11.
Toxicol Appl Pharmacol ; 394: 114950, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32147540

RESUMEN

The hypothalamic paraventricular nucleus (PVN) plays crucial roles in central cardiovascular regulation. Increasing evidence in humans and rodents shows that vitamin D intake is important for achieving optimal cardiovascular function. The purpose of this study was to investigate whether calcitriol, an active form of vitamin D, improves autonomic and cardiovascular function in hypertensive rats and whether PVN oxidative stress and inflammation are involved in these beneficial effects. Male spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were treated with either calcitriol (40 ng/day) or vehicle (0.11 µL/h) through chronic PVN infusion for 4 weeks. Blood pressure and heart rate were recorded continuously by radiotelemetry. PVN tissue, heart and plasma were collected for molecular and histological analysis. Compared to WKY rats, SHR exhibited increased systolic blood pressure, sympathetic drive, and cardiac hypertrophy and remodeling. These were associated with higher mRNA and protein expression levels of high mobility box 1 (HMGB1), receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), proinflammatory cytokines, NADPH oxidase subunit in the PVN. In addition, increased norepinephrine in plasma, elevated reactive oxygen species levels and activation of microglia in the PVN were also observed in SHR. Chronic calcitriol treatment ameliorated these changes but not in WKY rats. Our results demonstrate that chronic infusion of calcitriol in the PVN ameliorates hypertensive responses, sympathoexcitation and retains cardiovascular function in SHR. Reduced inflammation and oxidative stress within the PVN are involved in these calcitriol-induced effects.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Enfermedades del Sistema Nervioso Autónomo/tratamiento farmacológico , Calcitriol/uso terapéutico , Agonistas de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Animales , Enfermedades del Sistema Nervioso Autónomo/genética , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/prevención & control , Regulación de la Expresión Génica/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/genética , Masculino , Estrés Oxidativo/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY
13.
J Dermatolog Treat ; 31(1): 18-26, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30663443

RESUMEN

Pruritus, a very broad, subjective, and complex symptom, troubles the majority of patients with psoriasis. However, the subjective and multidimensional nature of the symptom renders it challenging for patients to appropriately communicate their experiences with itch to providers. This review explores current perspectives regarding the underlying mechanisms, assessment tools, burden, and treatment modalities for psoriatic pruritus. It emphasizes the significance of incorporating a standardized, thorough, and verified metric that incorporates severity, distribution, and character of pruritus as well as its effects on various aspects of quality of life. It also underscores the importance of continued research to fully understand the pathogenesis of psoriatic itch for establishment of novel, targeted therapeutics.


Asunto(s)
Prurito/etiología , Psoriasis/patología , Betametasona/uso terapéutico , Calcitriol/análogos & derivados , Calcitriol/uso terapéutico , Costo de Enfermedad , Fármacos Dermatológicos/uso terapéutico , Humanos , Prurito/psicología , Prurito/terapia , Psoriasis/complicaciones , Calidad de Vida , Índice de Severidad de la Enfermedad
14.
Clin Exp Dermatol ; 45(3): 318-322, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31419323

RESUMEN

Psoriasis is commonly treated with topical corticosteroids, oral cytotoxic drugs and biologic agents, which can be associated with significant adverse effects (AEs), high cost and response attenuation. Additionally, patients often use alternative therapies ad hoc, which can be challenging to integrate into a treatment regimen, owing to a lack of adequately powered controlled trials assessing efficacy and safety. We developed a novel topical botanical complex, herbal anti-inflammatory treatment (HAT1), through extensive preclinical in vitro and in vivo modelling to define key mechanisms of action and clinical potential. To assess the efficacy and safety of HAT1 in psoriasis, we performed a 10-week, open-label, pilot clinical trial comparing topical treatment of HAT1 with calcipotriol 0.005% in adult patients with mild to moderate psoriasis. Primary and secondary endpoints included the percentage of patients obtaining improvement of ≥ 75% in Psoriasis Area and Severity Index (PASI 75), Physician's Global Assessment (PGA) response, and evaluation of tolerability and safety of HAT1. In the HAT1 arm, 85.7% of study patients reached PASI 75 compared with 21.4% in the calcipotriol comparator group. Additionally, 78.6% of patients in the HAT1 arm achieved a 'clear' or 'minimal' PGA response. HAT1 was well tolerated, with no AEs observed throughout the trial. These results suggest that HAT1 reduces psoriasis disease activity in a clinically relevant manner. Ongoing studies, including well-powered, double-blind, randomized controlled trials will be required to assess the potential of HAT1 in psoriasis.


Asunto(s)
Antiinflamatorios/uso terapéutico , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapéutico , Extractos Vegetales/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Tópica , Adolescente , Adulto , Antiinflamatorios/efectos adversos , Calcitriol/efectos adversos , Calcitriol/uso terapéutico , Niño , Enfermedad Crónica , Fármacos Dermatológicos/efectos adversos , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Proyectos Piloto , Extractos Vegetales/efectos adversos , Adulto Joven
15.
J Dermatol ; 47(2): 155-162, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31762070

RESUMEN

Psoriasis is a T-helper (Th)1/Th17-mediated, chronic inflammatory dermatitis that is commonly treated with topical corticosteroids and vitamin D3 analogs. The combination of a topical corticosteroid and vitamin D3 analog showed superior efficacy to each alone in clinical trials; however, the mechanisms by which the topical corticosteroid and vitamin D3 analog exert their effects on lesional skin in combination and each alone remain unknown. In this study, we examined the effects of combined calcipotriol (Cal)/betamethasone dipropionate (BD) ointment on psoriasis in vivo, utilizing imiquimod (IMQ)-induced murine psoriasiform skin inflammation, compared with each alone. Vehicle, Cal/BD, Cal or BD was applied on the shaved back skin for 3 consecutive days. Then, IMQ was applied for 6 consecutive days. Twenty-four hours after the last IMQ treatment, the murine skin was evaluated clinically and pathologically. mRNA expressions were examined by quantitative polymerase chain reaction. All ointments alleviated IMQ-induced psoriasiform skin inflammation clinically in comparison with vehicle application. Cal/BD suppressed mRNA expressions of cytokines involved in psoriasis pathogenesis such as interleukin (IL)-17A and IL-22 efficiently. Cal alone induced IL-10 expression, whereas BD alone reduced IL-6 mRNA expression and the number of phosphorylated signal transducer and activator of transcription 3-positive cells in lesional skin. Our study revealed that Cal and BD have different effects on IMQ-induced psoriasiform skin. Some of the immune effects of Cal and BD may be additive or synergistic, which may account for the superior clinical efficacy of their combination.


Asunto(s)
Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Fármacos Dermatológicos/farmacología , Glucocorticoides/fisiología , Psoriasis/tratamiento farmacológico , Administración Cutánea , Animales , Betametasona/farmacología , Betametasona/uso terapéutico , Calcitriol/farmacología , Calcitriol/uso terapéutico , Citocinas/metabolismo , Fármacos Dermatológicos/uso terapéutico , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Glucocorticoides/uso terapéutico , Humanos , Imiquimod/toxicidad , Ratones , Pomadas , Psoriasis/sangre , Psoriasis/inmunología , Psoriasis/patología , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células TH1/metabolismo , Células Th17/efectos de los fármacos , Células Th17/inmunología , Células Th17/metabolismo
16.
J Neuroimmunol ; 338: 577079, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31731230

RESUMEN

Experimental autoimmune encephalomyelitis (EAE) is a common animal model that has the same pathology and pathogenesis as multiple sclerosis (MS). Dendritic cells (DCs) exert an important role in central and peripheral tolerance. DCs not only drive T cell priming and differentiation via playing antigen presentation function but mediate the resolution of advancing immune responses with its tolerogenic effect. In this study, we employed 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to induce tolerogenic dendritic cells (VD3-DCs) revealing their therapeutic effect through an increase in the development of the negative regulatory signaling pathway programmed death 1 (PD1)/programmed death ligand 1 (PDL1).


Asunto(s)
Antígeno B7-H1/análisis , Calcitriol/uso terapéutico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/análisis , Animales , Antígeno B7-H1/fisiología , Calcitriol/farmacología , Células Dendríticas/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple/inmunología , Receptor de Muerte Celular Programada 1/fisiología , Linfocitos T/inmunología
17.
Trials ; 20(1): 674, 2019 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-31801593

RESUMEN

BACKGROUND: Psoriasis is a chronic, immune-mediated disorder with chronic plaque psoriasis being the primary manifestation during the remission stage. Patients often have a slow course and long history of the disease. The refractory type of psoriasis is a stubborn rash that does not subside easily. We designed this randomized controlled trial to compare the effectiveness and relapse rates of plaque psoriasis in patients treated with either acupuncture, moxibustion or calcipotriol ointment. The ultimate aim of the study is to select an effective traditional Chinese medicine therapy for patients with plaque psoriasis. METHODS: The study will be a multicenter, prospective, randomized controlled trial that compares the effectiveness of fire needle therapy, moxibustion and calcipotriol ointment. In total, 160 patients with plaque psoriasis who meet the inclusion criteria will be recruited from three hospitals in Beijing and then randomly assigned to receive either fire needle therapy (group A1), moxibustion (group A2) or calcipotriol ointment (group B). All participants will receive an 8-week treatment and will then be followed up for another 24 weeks, with time points at weeks 12 and 24 after treatment completion. The primary outcomes to be measured are relapse rates and psoriasis area and severity index score of the target lesions. In addition, the target lesion onset time, dermatology life quality index, traditional Chinese medicine syndrome score, and the relapse interval of the target lesion will be measured. Adverse events will be recorded for safety assessment. DISCUSSION: The aim of this study is to determine whether fire needle therapy or moxibustion could improve the clinical effectiveness for psoriasis lesions and reduce the relapse rate. Once completed, it will provide information regarding therapeutic evaluation on fire needle therapy or moxibustion for plaque psoriasis, which will assist clinicians in selecting the most effective treatment options for patients. TRIAL REGISTRATION: International Clinical Trials Registry Platform (ICTRP), ChiCTR1800019588. Registered on 19 November 2018.


Asunto(s)
Terapia por Acupuntura/métodos , Moxibustión/métodos , Psoriasis/terapia , Adolescente , Adulto , Anciano , Calcitriol/análogos & derivados , Calcitriol/uso terapéutico , Enfermedad Crónica , Humanos , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Adulto Joven
18.
JAMA Netw Open ; 2(12): e1917789, 2019 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-31860103

RESUMEN

Importance: Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness. Objective: To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs. Data Sources: PubMed, EMBASE, Cochrane Library, and other RCT databases were searched from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018. Study Selection: Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared vitamin D or vitamin D and calcium with control. Data Extraction and Synthesis: Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and assessed possible bias. Rate ratios (RRs) were estimated using fixed-effects meta-analysis. Data extraction and synthesis took place between July 2018 and June 2019. Main Outcomes and Measures: Any fracture and hip fracture. Results: In a meta-analysis of 11 observational studies (39 141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted RR for hip fracture of 0.80 (95% CI, 0.75-0.86). A meta-analysis of 11 RCTs (34 243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30 000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06; 95% CI, 0.98-1.14) or hip fracture (RR, 1.14; 95% CI, 0.98-1.32), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants. In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (RR, 0.84; 95% CI, 0.72-0.97). Conclusions and Relevance: In this systematic review and meta-analysis, neither intermittent nor daily dosing with standard doses of vitamin D alone was associated with reduced risk of fracture, but daily supplementation with both vitamin D and calcium was a more promising strategy.


Asunto(s)
Calcitriol/uso terapéutico , Suplementos Dietéticos/estadística & datos numéricos , Fracturas Óseas/prevención & control , Vitamina D/análogos & derivados , Conservadores de la Densidad Ósea/uso terapéutico , Huesos/efectos de los fármacos , Fracturas Óseas/sangre , Fracturas de Cadera/prevención & control , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina D/sangre
19.
BMJ Case Rep ; 12(12)2019 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-31857291

RESUMEN

We report a rare case of type 2 diabetes mellitus (T2DM) complicated with idiopathic hypoparathyroidism. A 36-year-old Japanese man was admitted to our hospital owing to poor glycaemic control and hypocalcaemia. The patient had myalgia resulting from hypocalcaemia, which prevented adequate exercise. He considered the onset of myalgia to be an adverse event of oral hypoglycaemic agents and reduced compliance to medication; however, his serum calcium level was never measured. Treatment for hypocalcaemia immediately improved the myalgia, facilitating regular exercise therapy and ensuring compliance with prescribed medications, as the now-resolved myalgia was no longer perceived to be an adverse effect of glucose-lowering agents; this improved glycaemic control. Although hypoparathyroidism is a rare disease, it is necessary to assess serum calcium levels in patients with T2DM, particularly in cases presenting with unidentified complaints such as myalgia.


Asunto(s)
Diabetes Mellitus Tipo 2/diagnóstico , Hipoparatiroidismo/diagnóstico , Adulto , Glucemia , Calcitriol/administración & dosificación , Calcitriol/uso terapéutico , Terapia Combinada , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diagnóstico Diferencial , Terapia por Ejercicio , Hemoglobina A Glucada , Humanos , Hipocalcemia/etiología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Hipoparatiroidismo/sangre , Hipoparatiroidismo/complicaciones , Masculino , Mialgia/etiología
20.
Int J Mol Sci ; 21(1)2019 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-31861934

RESUMEN

An exopolysaccharides/calcipotriol (EPS/CPT) emulsion was prepared using bacterial EPS as emulsifier, sunflower oil as an oil phase and CPT as the loaded drug, and the effect of this emulsion on psoriasis vulgaris treatment was evaluated. An EPS composed of mannose (70.56%) and glucose (29.44%) was obtained from the marine mangrove bacteria Bacillus amyloliquefaciens ZWJ (Zhu Wenjing) strain. The EPS has significant emulsifying activity at the concentration of 1.5%. The prepared EPS/CPT emulsion has small and stable particle size, with a drug content of 0.00492%, and good spreading properties. The in vitro drug release results revealed that the emulsion showed a certain sustained release effect. In vitro and in vivo animal experiments show that the EPS/CPT emulsion can effectively treat psoriasis vulgaris by increasing the accumulation of CPT in psoriatic skin lesions and reducing the levels of inflammatory cells and inflammatory factors (TNF and IL6). Additionally, it has a certain effect on reducing the side effects associated with CPT. This study lays a foundation for the research of EPS in the topical application of medical materials and treatment of psoriasis.


Asunto(s)
Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapéutico , Emulsionantes/uso terapéutico , Polisacáridos Bacterianos/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Cutánea , Animales , Bacillus amyloliquefaciens/química , Calcitriol/administración & dosificación , Calcitriol/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Emulsionantes/administración & dosificación , Emulsionantes/química , Masculino , Ratones , Polisacáridos Bacterianos/administración & dosificación , Polisacáridos Bacterianos/química , Psoriasis/patología
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