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1.
Arch Dermatol Res ; 316(5): 190, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775976

RESUMEN

Hair is a biofilament with unique multi-dimensional values. In human, in addition to physiologic impacts, hair loss and hair related disorders can affect characteristic features, emotions, and social behaviors. Despite significant advancement, there is a dire need to explore alternative novel therapies with higher efficacy, less side effects and lower cost to promote hair growth to treat hair deficiency. Glucocorticoid-induced leucine zipper (GILZ) is a protein rapidly induced by glucocorticoids. Studies from our group and many others have suggested that a synthetic form of GILZ, TAT-GILZ, a fusion peptide of trans-activator of transcription and GILZ, can function as a potent regulator of inflammatory responses, re-establishing and maintaining the homeostasis. In this study, we investigate whether TAT-GILZ could promote and contribute to hair growth. For our pre-clinical model, we used 9-12 week-old male BALB/c and nude (athymic, nu/J) mice. We applied TAT-GILZ and/or TAT (vehicle) intradermally to depilated/hairless mice. Direct observation, histological examination, and Immunofluorescence imaging were used to assess the effects and compare different treatments. In addition, we tested two current treatment for hair loss/growth, finasteride and minoxidil, for optimal evaluation of TAT-GILZ in a comparative fashion. Our results showed, for the first time, that synthetic TAT-GILZ peptide accelerated hair growth on depilated dorsal skin of BALB/c and induced hair on the skin of athymic mice where hair growth was not expected. In addition, TAT-GILZ was able to enhance hair follicle stem cells and re-established the homeostasis by increasing counter inflammatory signals including higher regulatory T cells and glucocorticoid receptors. In conclusion, our novel findings suggest that reprofiling synthetic TAT-GILZ peptide could promote hair growth by increasing hair follicle stem cells and re-establishing homeostasis.


Asunto(s)
Alopecia , Folículo Piloso , Cabello , Factores de Transcripción , Animales , Masculino , Ratones , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Humanos , Alopecia/tratamiento farmacológico , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ratones Endogámicos BALB C , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/administración & dosificación , Ratones Desnudos , Ratones Pelados , Modelos Animales de Enfermedad , Glucocorticoides/farmacología
2.
Pediatr Transplant ; 28(4): e14768, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38770694

RESUMEN

BACKGROUND: Immunosuppression of pediatric kidney transplant (PKT) recipients often includes corticosteroids. Prolonged corticosteroid exposure has been associated with secondary adrenal insufficiency (AI); however, little is known about its impact on PKT recipients. METHODS: This was a retrospective cohort review of PKT recipients to evaluate AI prevalence, risk factors, and adverse effects. AI risk was assessed using morning cortisol (MC) and diagnosis confirmed by an ACTH stimulation test. Potential risk factors and adverse effects were tested for associations with MC levels and AI diagnosis. RESULTS: Fifty-one patients (60.8% male, age 7.4 (IQR 3.8, 13.1) years; 1 patient counted twice for repeat transplant) were included. Patients at risk for AI (MC < 240 nmol/L) underwent definitive ACTH stimulation testing, confirming AI in 13/51 (25.5%) patients. Identified risk factors for AI included current prednisone dosage (p = .001), 6-month prednisone exposure (p = .02), daily prednisone administration (p = .002), and rejection episodes since transplant (p = .001). MC level (2.5 years (IQR 1.1, 5.1) post-transplant) was associated with current prednisone dosage (p < .001), 6-month prednisone exposure (p = .001), daily prednisone administration (p = .006), rejection episodes since transplant (p = .003), greater number of medications (ß = -16.3, p < .001), 6-month hospitalization days (ß = -3.3, p = .013), creatinine variability (ß = -2.4, p = .025), and occurrence of acute kidney injury (ß = -70.6, p = .01). CONCLUSION: Greater corticosteroid exposure was associated with a lower MC level and confirmatory diagnosis of AI noted with an ACTH stimulation test. Adverse clinical findings with AI included greater medical complexity and kidney function lability. These data support systematic clinical surveillance for AI in PKT recipients treated with corticosteroids.


Asunto(s)
Insuficiencia Suprarrenal , Trasplante de Riñón , Prednisona , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/etiología , Insuficiencia Suprarrenal/epidemiología , Femenino , Estudios Retrospectivos , Niño , Adolescente , Factores de Riesgo , Preescolar , Prednisona/uso terapéutico , Hidrocortisona/sangre , Prevalencia , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Glucocorticoides/uso terapéutico , Hormona Adrenocorticotrópica/sangre , Rechazo de Injerto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología
3.
Biol Pharm Bull ; 47(5): 965-966, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38763750

RESUMEN

The emergence of coronavirus disease 2019 (COVID-19), a novel identified pneumonia resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has significantly impacted and posed significant challenges to human society. The papain-like protease (PLpro) found in the nonstructural protein 3 of SARS-CoV-2 plays a vital role in viral replication. Moreover, PLpro disrupts the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 from host proteins. Consequently, PLpro has emerged as a promising drug target against SARS-CoV-2 infection. Computational studies have reported that ciclesonide can bind to SARS-CoV-2 PLpro. However, the inhibitory effects of ciclenoside on the PLpro have not been experimentally evaluated. Here, we evaluated the inhibitory effects of synthetic glucocorticoids (sGCs), including ciclesonide, on SARS-CoV-2 PLpro in vitro assay. Ciclesonide significantly inhibited the enzymatic activity of PLpro, compared with other sGCs and its IC50 was 18.4 ± 1.89 µM. These findings provide insights into the development of PLpro inhibitors.


Asunto(s)
Pregnenodionas , SARS-CoV-2 , Pregnenodionas/farmacología , SARS-CoV-2/efectos de los fármacos , Humanos , Tratamiento Farmacológico de COVID-19 , Proteasas Similares a la Papaína de Coronavirus/antagonistas & inhibidores , Proteasas Similares a la Papaína de Coronavirus/metabolismo , Antivirales/farmacología , Simulación del Acoplamiento Molecular , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Glucocorticoides/farmacología , COVID-19/virología
4.
Adv Rheumatol ; 64(1): 38, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720354

RESUMEN

BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.


Asunto(s)
Antimaláricos , Azatioprina , Glucocorticoides , Hidroxicloroquina , Inmunosupresores , Lupus Eritematoso Sistémico , Metotrexato , Prednisolona , Nivel de Atención , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Femenino , Inmunosupresores/uso terapéutico , Hidroxicloroquina/uso terapéutico , Masculino , Glucocorticoides/uso terapéutico , Adulto , Azatioprina/uso terapéutico , Prednisolona/uso terapéutico , Metotrexato/uso terapéutico , Antimaláricos/uso terapéutico , Estudios de Cohortes , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Leflunamida/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Modelos Logísticos , Puntaje de Propensión , Índice de Severidad de la Enfermedad , Tacrolimus/uso terapéutico , Brote de los Síntomas , Resultado del Tratamiento , Antirreumáticos/uso terapéutico
5.
Adv Exp Med Biol ; 1447: 191-207, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38724794

RESUMEN

Atopic dermatitis has a substantial impact on sleep, appearance, psychological well-being, and other qualities of life. The visual appearance of lichenification, cheilitis, hyperpigmentation, ichthyosis, and erythema can be socially stigmatizing, and treatment of these symptoms is challenging. In managing pruritus in patients, practitioners should assess and document pruritus through questionnaires at each routine visit. Initially, practitioners should advise patients to employ nonpharmaceutical treatments such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions. If these methods of treatment are not successful or if the disease presentation is severe, pharmacological therapies should be employed. This chapter describes the therapeutic ladder for pruritus in atopic dermatitis and discusses each treatment modality in further detail for practitioners to advise their patients.First-line topical pharmaceutical agents include topical glucocorticoids and topical calcineurin inhibitors. Second-line topical agents include coal tar, menthol, capsaicin, or doxepin. After the use of topical agents has been exhausted, primary systemic agents can be applied. These include sedating antihistamines, nonsedating antihistamines, oral glucocorticoids, or cyclosporine A. Finally, neuromodulating or immunomodulating agents can be attempted, including SSRI/SNRIs, TCAs, immunosuppressants, neural modulators, and opioid receptor modulators. Outside of pharmacological treatments, phototherapy has been shown to provide a dramatic improvement of pruritus in atopic dermatitis and can be used at any stage of treatment including as a first-line agent.


Asunto(s)
Dermatitis Atópica , Prurito , Humanos , Antipruriginosos/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Dermatitis Atópica/terapia , Dermatitis Atópica/complicaciones , Glucocorticoides/uso terapéutico , Antagonistas de los Receptores Histamínicos/uso terapéutico , Fototerapia/métodos , Prurito/terapia , Prurito/etiología , Prurito/fisiopatología , Prurito/tratamiento farmacológico
6.
Front Immunol ; 15: 1366101, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707905

RESUMEN

We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2019, resulting in complete remission. However, he was diagnosed in 2021 with several autoimmune disorders, including autoimmune hepatitis (AIH), Hashimoto's thyroiditis (HT), and autoimmune hemolytic anemia (AIHA). This is referred as multiple autoimmune syndrome (MAS), which is a rare occurrence after allo-HSCT, as previously noted in the literature. Despite being treated with glucocorticoids, cyclosporine A, and other medications, the patient did not fully recover. To address the glucocorticoid-refractory MAS, a four-week course of rituximab (RTX) at a weekly dose of 100mg was administered, which significantly improved the patient's condition. Thus, this case report underscores the importance of implementing alternative treatments in patients with post-transplant autoimmune diseases, who are glucocorticoid-refractory or glucocorticoid-dependent, and highlights the effectiveness of RTX as second-line therapy.


Asunto(s)
Enfermedades Autoinmunes , Glucocorticoides , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Persona de Mediana Edad , Glucocorticoides/uso terapéutico , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/terapia , Rituximab/uso terapéutico , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Resistencia a Medicamentos
8.
Eur J Endocrinol ; 190(5): G25-G51, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38714321

RESUMEN

Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.


Asunto(s)
Insuficiencia Suprarrenal , Endocrinología , Glucocorticoides , Humanos , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/inducido químicamente , Insuficiencia Suprarrenal/terapia , Insuficiencia Suprarrenal/tratamiento farmacológico , Endocrinología/normas , Endocrinología/métodos , Europa (Continente) , Sociedades Médicas/normas
10.
Neuron ; 112(9): 1373-1375, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38697018

RESUMEN

Maternal well-being is important for the development of the fetus, with a key influence on its nervous system. In this issue of Neuron, Krontira et al.1 implicate glucocorticoids, the stress hormones, in the regulation of neural stem cell identity and proliferation, with long-lasting consequences on brain architecture and educational attainment.


Asunto(s)
Glucocorticoides , Neurogénesis , Humanos , Glucocorticoides/farmacología , Neurogénesis/efectos de los fármacos , Neurogénesis/fisiología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/citología , Células-Madre Neurales/efectos de los fármacos
12.
J Orthop Surg Res ; 19(1): 292, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735955

RESUMEN

BACKGROUND: In this retrospective case investigation, we analysed the data of patients with osteonecrosis of the femoral head (ONFH) to reveal demographic and clinical diagnostic features of ONFH in three northeastern provinces of China and provide a reference for its prevention, diagnosis, and treatment. METHODS: We collected data from patients in Beijing Orthopaedic Hospital of Liaoning, focusing on the aetiology and diagnosis of ONFH. Medical records and self-designed questionnaires were used to collect information for statistical analysis, including age, aetiology, reason for glucocorticoid use, hospital level at first visit, and diagnosis. RESULTS: In total, 906 patients with complete medical records were included in the analysis. The mean patient age was 47.65 ± 12.12 years. The peak age distribution was in the 40s for men and the 50s for women. Among the total cohort, 72 patients (7.95%; 40 men and 32 women) had traumatic ONFH, 198 (21.85%; 131 men and 67 women) had steroid-induced ONFH, 230 (25.39%; 121 men and 109 women) had idiopathic ONFH, and 406 (44.81%; 397 men and 9 women) had alcohol-induced ONFH. Six hundred and twenty patients were diagnosed with ONFH at the first visit, while 286 patients were misdiagnosed, with a diagnosis rate of 68.43%. The diagnosis rate at the first visit in tertiary hospitals was 76.14%. The diagnosis rate at the first visit in second-class hospitals was 52.07%.ONFH was most likely to be misdiagnosed as lumbar disc herniation. CONCLUSIONS: Most patients with ONFH in three northeastern provinces of China were middle-aged, male, and had alcohol-induced ONFH. The misdiagnosis rate of ONFH at the first visit was very high, especially for misdiagnosis of lumbar disc herniation, indicating that the diagnosis of ONFH requires further improvement.


Asunto(s)
Necrosis de la Cabeza Femoral , Humanos , Masculino , Femenino , Necrosis de la Cabeza Femoral/epidemiología , Necrosis de la Cabeza Femoral/diagnóstico , Necrosis de la Cabeza Femoral/etiología , Persona de Mediana Edad , Adulto , China/epidemiología , Estudios Retrospectivos , Anciano , Adulto Joven , Adolescente , Glucocorticoides/uso terapéutico
14.
Cancer Cell ; 42(5): 833-849.e12, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38701792

RESUMEN

Glucocorticoids have been used for decades to treat lymphomas without an established mechanism of action. Using functional genomic, proteomic, and chemical screens, we discover that glucocorticoids inhibit oncogenic signaling by the B cell receptor (BCR), a recurrent feature of aggressive B cell malignancies, including diffuse large B cell lymphoma and Burkitt lymphoma. Glucocorticoids induce the glucocorticoid receptor (GR) to directly transactivate genes encoding negative regulators of BCR stability (LAPTM5; KLHL14) and the PI3 kinase pathway (INPP5D; DDIT4). GR directly represses transcription of CSK, a kinase that limits the activity of BCR-proximal Src-family kinases. CSK inhibition attenuates the constitutive BCR signaling of lymphomas by hyperactivating Src-family kinases, triggering their ubiquitination and degradation. With the knowledge that glucocorticoids disable oncogenic BCR signaling, they can now be deployed rationally to treat BCR-dependent aggressive lymphomas and used to construct mechanistically sound combination regimens with inhibitors of BTK, PI3 kinase, BCL2, and CSK.


Asunto(s)
Glucocorticoides , Receptores de Antígenos de Linfocitos B , Humanos , Glucocorticoides/farmacología , Receptores de Antígenos de Linfocitos B/metabolismo , Animales , Transducción de Señal/efectos de los fármacos , Receptores de Glucocorticoides/metabolismo , Ratones , Línea Celular Tumoral , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patología , Terapia Molecular Dirigida/métodos , Fosfatidilinositol 3-Quinasas/metabolismo , Familia-src Quinasas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
16.
J Orthop Surg (Hong Kong) ; 32(2): 10225536241256554, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753310

RESUMEN

BACKGROUND: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. METHODS: A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. RESULTS: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. CONCLUSIONS: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Dexametasona , Glucocorticoides , Dolor Postoperatorio , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Masculino , Glucocorticoides/administración & dosificación , Femenino , Inyecciones Intraarticulares , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/diagnóstico , Dexametasona/administración & dosificación , Inyecciones Intravenosas , Dimensión del Dolor , Cuidados Intraoperatorios/métodos , Resultado del Tratamiento , Rango del Movimiento Articular
17.
BMJ Open Gastroenterol ; 11(1)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38719549

RESUMEN

BACKGROUND AND OBJECTIVE: The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES: A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded. RESULTS: There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p<0.05). Similar data were seen at week 52. Prednisolone did not affect infliximab trough levels but increased infection rates (10/77 vs 2/70, p=0.03), in particular C. difficile infection. CONCLUSION: In UC patients with limited disease burden, prednisolone did not affect effectiveness of infliximab. However, patients with increased disease burden seem to benefit from corticosteroid combination therapy.


Asunto(s)
Colitis Ulcerosa , Fármacos Gastrointestinales , Infliximab , Prednisolona , Inducción de Remisión , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Infliximab/administración & dosificación , Infliximab/uso terapéutico , Estudios Retrospectivos , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Inducción de Remisión/métodos , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/uso terapéutico , Reducción Gradual de Medicamentos/métodos , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Antiinflamatorios/efectos adversos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Quimioterapia Combinada
18.
Am J Case Rep ; 25: e943597, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38769718

RESUMEN

BACKGROUND Nephrogenic diabetes insipidus (NDI) is a rare renal disorder that can be congenital, and is caused by mutations in either aquaporin 2 or arginine vasopressin receptor 2, or it can be secondary to kidney disease or electrolyte imbalance. The clinical signs of NDI include polyuria, compensatory polydipsia, hypernatremic dehydration, and growth retardation without prompt treatment. In this report, we present the case of a patient with congenital NDI who was later diagnosed with acute lymphoblastic leukemia (ALL). With dexamethasone treatment, he had uncontrolled polyuria and polydipsia. Our aim was to concentrate on the impact of steroids on the kidneys. CASE REPORT Our patient presented at the age of 9 months with signs of severe dehydration that were associated with polyuria. His laboratory examinations revealed hypernatremia and decreased urine osmolality. He was diagnosed with NDI and his exome sequence revealed a homozygous mutation at the nucleotide position AQP2 NM_000486.6: c.374C>T (p.Thr125Met). He was treated with hydrochlorothiazide and amiloride. Then, at age 19 months, he presented with gastroenteritis and a complete blood count (CBC) showed high white blood cell count and blast cells. He was diagnosed with (ALL) and began receiving chemotherapy, during which again developed polydipsia and polyuria, which could not be controlled with an increased dosage of hydrochlorothiazide. CONCLUSIONS We report a rare case of NDI caused by a missense mutation in the aquaporin 2 gene. One year later, the child developed ALL, and treatment with dexamethasone led to an uncompensated state of polydipsia and polyuria.


Asunto(s)
Acuaporina 2 , Diabetes Insípida Nefrogénica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Diabetes Insípida Nefrogénica/genética , Acuaporina 2/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Lactante , Dexametasona/uso terapéutico , Mutación , Glucocorticoides/uso terapéutico
19.
Front Endocrinol (Lausanne) ; 15: 1384365, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715797

RESUMEN

Importance: Subacute thyroiditis (SAT) is a self-limiting and inflammatory thyroid disease. Although SAT usually improves on its own within weeks, it needs treatment when patients have pain, fever, and symptoms of thyrotoxicosis. Therapeutic drugs mainly include non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Currently, there is no systematic review or meta-analysis of the comparison of outcomes between NSAIDs and glucocorticoids for the treatment of SAT. Objectives: To conduct a systematic review and meta-analysis on the outcomes in subacute thyroiditis patients treated with glucocorticoids or NSAIDs. Data sources: Using the four electronic databases, including PubMed, Embase, Cochrane Library, Wanfang database and Web of Science. All publications until 21 June 2023 were searched. The reference lists of all selected articles were independently screened to identify additional studies left out in the initial search. Study selection: The literature comparing outcomes between glucocorticoids and non-steroidal anti-inflammatory drugs for patients with subacute thyroiditis will be included. Data extraction and synthesis: Two independent investigators (Anqi Yuan and Jialu Wu) extracted the data following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (PRISMA) and then evaluated the quality of the eligible studies with the Newcastle-Ottawa Scale. Fixed-effects models for the meta-analyses were applied. Heterogeneity was assessed with the chi-squared (x²) test (Cochran's Q) and inconsistency index (I²). The robustness of the results was tested with the sensitivity analyses. The bias of publication was assessed with the Harbord test. Main outcomes and measures: The incidence of permanent hypothyroidism in SAT patients treated with corticosteroids or NSAIDs. Results: Our study included a total of ten comparative cohort studies with 1337 participants. We found that the incidence of developing permanent hypothyroidism in the SAT patients who received glucocorticoids treatment was significantly lower than those who received NSAIDs treatment. (OR, 0.56; 95% CI, 0.36-0.88; P = 0.01). The risk of permanent hypothyroidism in patients who received prednisone at an average initial dose < 40 mg/d was significantly lower than that in patients who received NSAIDs (OR, 0.37; 95% CI, 0.14-0.94; P = 0.04). There was no significant difference in the occurrence of permanent hypothyroidism between SAT patients who received an average initial dose ≥ 40 mg/d of prednisone and those who received only NSAIDs (OR, 0.7; 95% CI, 0.14-3.53; P = 0.67). In addition, the recurrence rate was observably higher in those receiving glucocorticoids than in those receiving NSAIDs (OR, 1.98; 95% CI, 1.12-3.5; p = 0.02). The recurrence rate was significantly higher in patients with an average initial prednisone dose of < 40 mg/d than in the NSAIDs group. There was no significant difference in the recurrence rate between patients in the mean initial prednisone dose ≥ 40 mg/d group and those in the NSAIDs group. Conclusions and relevance: In this meta-analysis, we compared the treatment outcomes of SAT patients between glucocorticoids and NSAIDs. Our results indicated that glucocorticoid treatment was associated with a lower incidence of permanent hypothyroidism than NSAID treatment. Patients treated with NSAIDs might have a lower recurrence rate. This finding might help to understand the outcome of the disease when choosing different drugs and help physicians to make appropriate decisions. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023427332.


Asunto(s)
Antiinflamatorios no Esteroideos , Glucocorticoides , Tiroiditis Subaguda , Humanos , Antiinflamatorios no Esteroideos/uso terapéutico , Tiroiditis Subaguda/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Glucocorticoides/administración & dosificación , Resultado del Tratamiento
20.
BMJ Case Rep ; 17(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697679

RESUMEN

Ornithine transcarbamylase deficiency (OTCD) is a rare, X linked disorder that can manifest in late adulthood in heterozygous females as severe hyperammonaemia following environmental stressors. We present a case of hyperammonaemic encephalopathy that was triggered by glucocorticoid administration in an adult woman with heterozygous OTCD with clinical response to haemodialysis, ammonia scavengers and a high-calorie, low-protein diet.


Asunto(s)
Hiperamonemia , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa , Humanos , Femenino , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/complicaciones , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/diagnóstico , Hiperamonemia/inducido químicamente , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Diálisis Renal , Encefalopatías/inducido químicamente , Encefalopatías/etiología , Persona de Mediana Edad , Dieta con Restricción de Proteínas/efectos adversos
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