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1.
Surg Clin North Am ; 99(6): 1223-1235, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676060

RESUMO

Inflammatory bowel disease has become a growing concern worldwide. The chronic and progressive nature of inflammatory bowel disease poses significant challenges to the treatment and management of affected patients, straining health care resources. Therapeutic options and optimal management strategies have evolved dramatically. The treat-to-target strategy has shifted focus toward identifiable and attainable treatment targets and with the ability to optimize tight control. Advancements in our understanding of the pathophysiology led to therapeutic mechanisms that have a more narrowed focus toward gut-specific targets, improving safety profiles.


Assuntos
Produtos Biológicos/administração & dosagem , Tratamento Conservador/métodos , Imunossupressores/administração & dosagem , Doenças Inflamatórias Intestinais/terapia , Produtos Biológicos/farmacologia , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Seleção de Pacientes , Recidiva , Retratamento , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
2.
Medicine (Baltimore) ; 98(41): e17425, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593095

RESUMO

To evaluate whether the adult patients with acquired pure red cell aplasia (PRCA) could benefit more from cyclosporine A (CsA) combined with corticosteroids (CS) than CsA or CS alone.Seventy-three patients were evaluated in 2 institutions (6 patients lost to follow-up).The induction therapy included CsA (n = 21), CS (n = 21), or CsA combined with CS (n = 31), and remission was achieved in 16/21 (76.2%), 10/21 (47.6%), and 21/31 (71.0%) patients, respectively. Higher complete remission (CR) rate was achieved in CsA combined with CS group than in CS group (61.3% vs 19.0%, P = .003). Patients achieved CR faster in CsA combined with CS group than in CS group or CsA group (median time, 1 month vs 2 month vs 3 month, P = .010). By multivariate analysis, CsA combined with CS therapy and primary PRCA were the influence factors for CR rate. Twenty-seven patients relapsed due to discontinuation or tapering therapy, and 19 patients regained response by increasing the dose of original regimens or changing to other immunosuppressive therapy. Complete remission to induction therapy was a correlative factor for death (P = .035).CsA combined with CS produced faster and higher CR rate in treating adult patients with PRCA than did CsA or CS alone.


Assuntos
Corticosteroides/administração & dosagem , Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Quimioterapia de Indução/métodos , Aplasia Pura de Série Vermelha/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Expert Opin Drug Metab Toxicol ; 15(10): 803-811, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31595800

RESUMO

Introduction: Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplantation (HSCT); therefore, the prevention of GVHD is important for a successful treatment. Tacrolimus (Tac), a calcineurin inhibitor, has been widely used for the prophylaxis of GVHD in HSCT recipients. Areas covered: This review introduces phase II/III of clinical trials related with Tac's roles in the prevention of GVHD in HSCT. Furthermore, we discuss the normal ranges of Tac concentrations, pharmacogenetics, and drug interactions of Tac, as well as its side effects in adult HSCT recipients. Expert opinion: A series of studies has established the efficacy and safety of Tac alone or in combination with other agents in HSCT. However, successful administration of Tac is complicated by its narrow therapeutic window, inter-patient pharmacokinetic variability, and a spectrum of undesirable side effects. It is necessary to maintain concentrations of Tac within the desired ranges for GVHD prophylaxis. Moreover, various factors contribute to significant variability in Tac pharmacokinetics, including drug interactions and genomic variation.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Tacrolimo/administração & dosagem , Adulto , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacocinética , Interações de Medicamentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Farmacogenética , Tacrolimo/efeitos adversos , Tacrolimo/farmacocinética
4.
Expert Rev Clin Pharmacol ; 12(11): 1047-1057, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31575290

RESUMO

Introduction: The clinical use of tacrolimus is characterized by many side effects which include neurotoxicity. In contrast, tacrolimus has also shown to have neuroregenerative properties. On a molecular level, the mechanisms of action could provide us more insight into understanding the neurobiological effects. The aim of this article is to review current evidence regarding the use of tacrolimus in peripheral nerve injuries.Areas covered: Available data on tacrolimus' indications were summarized and molecular mechanisms were elucidated to possibly understand the conflicting neurotoxic and neuroregenerative effects. The potential clinical applications of tacrolimus, as immunosuppressant and enhancer of nerve regeneration in peripheral nerve injuries, are discussed. Finally, concepts of delivery are explored.Expert opinion: It is unclear what the exact neurobiological effects of tacrolimus are. Besides its known calcineurin inhibiting properties, the mechanism of action of tacrolimus is mediated by its binding to FK506-binding protein-52, resulting in a bimodal dose response. Experimental models found that tacrolimus administration is preferred up to three days prior to or within 10 days post-nerve reconstruction. Moreover, the indication for the use of tacrolimus has been expanding to fields of dermatology, ophthalmology, orthopedic surgery and rheumatology to improve outcomes after various indications.


Assuntos
Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Tacrolimo/administração & dosagem , Animais , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacologia , Esquema de Medicação , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Tacrolimo/efeitos adversos , Tacrolimo/farmacologia
5.
Internist (Berl) ; 60(10): 1059-1073, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31471629

RESUMO

Large-vessel vasculitis includes giant cell arteritis (GCA) and Takayasu arteritis (TA). GCA can affect persons from the age of 50 years and is more frequent among women. The disease course generally begins with an acute phase, with patients feeling very unwell and experiencing temporal headaches. Rapid diagnosis and treatment are necessary to reduce the risk of blindness. A suspected diagnosis must be confirmed by imaging, histology is optional. Initial treatment comprises oral prednisone. Recent studies have demonstrated inhibition of interleukin­6 with tocilizumab (TCZ) to be highly effective. Alternatively, methotrexate can be administered in a steroid-sparing approach. In contrast, TA onset is generally during childhood or adolescence, and begins with moderate systemic inflammation. The aorta and its main branches are affected. Treatment comprises steroids, disease-modifying antirheumatic drugs, and the tumor necrosis factor inhibitor infliximab or TCZ.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Arterite de Células Gigantes/tratamento farmacológico , Imunossupressores/administração & dosagem , Arterite de Takayasu/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Feminino , Células Gigantes , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Resultado do Tratamento
6.
J Drugs Dermatol ; 18(9): 947-949, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524994

RESUMO

Bullous pemphigoid (BP) is a rare blistering skin disease that is commonly treated with corticosteroids and immunosuppressive agents. Here, we present a 74-year-old woman with severe BP following a leg fracture who was successfully treated with omalizumab. We started her on a regimen of omalizumab 300 mg subcutaneously every 4 weeks, and within a week she reported significantly decreased pain and faster healing time of lesions. Incidentally, bilateral erythematous, non-blistering dermatitis developed 5 centimeters distal to the injection sites within a week of her first injection and resolved spontaneously in 2 days. She continues to tolerate the omalizumab injections well after 28 months of treatment and has not developed the injection site dermatitis since the first administration. Omalizumab appears to be a promising treatment modality for BP even when associated with transient injection site reactions, but further studies investigating the mechanisms by which omalizumab reduces bullae in BP are needed. J Drugs Dermatol. 2019;18(9):947-949.


Assuntos
Imunossupressores/administração & dosagem , Reação no Local da Injeção/etiologia , Omalizumab/administração & dosagem , Penfigoide Bolhoso/tratamento farmacológico , Idoso , Feminino , Humanos , Imunossupressores/efeitos adversos , Injeções Subcutâneas , Omalizumab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
7.
Expert Rev Clin Pharmacol ; 12(10): 973-980, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31550941

RESUMO

Introduction: Pemphigus, an autoimmune disease group characterized by blisters and erosions of the skin and/or mucosal membranes has been treated with systemic corticosteroids (CS) and immunosuppressive therapies for the past few decades. Areas Covered: However, common adverse effects and complications of long-term CS and immunosuppressive drugs are limiting their long-term use. The disease results in death if not treated. Thus, currently, researchers are trying to develop new and safer therapeutic approaches. Specifically, targeted therapies to pathogenic immune pathways are under investigation. The B cell inhibitors which block CD20 and CD19 are the main new drugs investigated in clinical trials as alternatives to systemic steroids. Expert Opinion: Randomized controlled trial (RCT) Level evidence shows that rituximab and short course CSs are more effective and safer than standard CS treatment. Specific BTK inhibitors have shown promise in data from a phase II international open-label study. Further studies are ongoing.


Assuntos
Corticosteroides/administração & dosagem , Imunossupressores/administração & dosagem , Pênfigo/tratamento farmacológico , Corticosteroides/efeitos adversos , Corticosteroides/farmacologia , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Animais , Desenvolvimento de Medicamentos/métodos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Terapia de Alvo Molecular , Pênfigo/imunologia , Pênfigo/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Fatores de Tempo
8.
Expert Opin Drug Saf ; 18(11): 1017-1030, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478398

RESUMO

Introduction: Human cytomegalovirus (HCMV) is a major contributor of morbidity and mortality, and its management is essential for the successful outcome of solid organ and hematopoietic stem cell transplantation. Areas covered: This review discusses the safety profiles of currently available and emerging antiviral drugs and the other strategies for HCMV prevention and treatment after transplantation. Expert opinion: Strategies for management of HCMV rely largely on the use of antiviral agents that inhibit viral DNA polymerase (ganciclovir/valganciclovir, foscarnet, and cidofovir/brincidofovir) and viral terminase complex (letermovir), with different types and degrees of adverse effects. An investigational agent, maribavir, exerts its anti-CMV effect through UL97 inhibition, and its safety profile is under clinical evaluation. In choosing the antiviral medication to use, it is important to consider these safety profiles in addition to overall efficacy. In addition to antiviral drugs, reduction of immunosuppression is often generally needed in the management of HCMV infection, but with a potential risk of allograft rejection or graft-versus-host disease. The use of HCMV-specific or non-specific intravenous immunoglobulins remains debated, while adoptive HCMV-specific T cell therapy remains investigational, and associated with unique set of adverse effects.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Infecções Oportunistas/prevenção & controle , Antivirais/efeitos adversos , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/administração & dosagem , Infecções Oportunistas/virologia , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos
9.
Pan Afr Med J ; 33: 116, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31489094

RESUMO

This study aims to analyze the epidemiological, clinical, therapeutic and evolutionary profile of ocular manifestations in patients with Behçet's disease. We conducted a retrospective, descriptive study of the medical records of 121 patients managed by specialists with expertise in this disease over a period of one year and a half between January 2015 and June 2016. The average age of patients was 35 years, 63.6% of patients were male, ocular involvement was inaugural in 24% of cases. Patients had anterior uveitis (7.4%), posterior uveitis (15.7%), vasculitis (19%), irido-crystalline synechias (17.5%), macular edema (7.4%), optic atrophy (4.1%), papillary edema (2.5%) and peripheral retinal ischemia (1.7%). In our series, 41.3% of patients were under colchicine, 23.1% under oral corticosteroids, 9% under intravenous corticosteroids, 4.9% under topical corticosteroids, 8.2% under immunosuppressive drugs and 5.8% under vitamin K antagonists. After an average follow-up of 1 year, 40% of patients had stable visual acuity while receiving treatment, 23% had a significant decrease in visual acuity and 5% of cases had complete vision loss. Adequate therapy enables quick containment of the infection and decreases the frequency and severity of recurrences, thus leading to an improvement of the visual prognosis in our patients compared with outcomes in some previous case serie.


Assuntos
Síndrome de Behçet/complicações , Oftalmopatias/etiologia , Acuidade Visual , Corticosteroides/administração & dosagem , Adulto , Colchicina/administração & dosagem , Oftalmopatias/epidemiologia , Oftalmopatias/fisiopatologia , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Prognóstico , Recidiva , Estudos Retrospectivos
10.
JAMA ; 322(10): 936-945, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503307

RESUMO

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01829295.


Assuntos
Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Uveíte/tratamento farmacológico , Adulto , Anti-Inflamatórios/administração & dosagem , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Testes de Função Hepática , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Prednisolona/administração & dosagem
11.
Vet Immunol Immunopathol ; 216: 109892, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446206

RESUMO

Cyclosporine and glucocorticoids are powerful immunosuppressive agents used to treat many inflammatory diseases in dogs. Cyclosporine inhibits calcineurin-dependent pathways of T cell activation and resultant T cell cytokine production, and glucocorticoids directly inhibit genes coding for cytokines. Little work has been done comparing the effects of these agents on T cell cytokine production in dogs. Our study measured T cell interleukin-2 (IL-2) and interferon-gamma (IFN-γ) production using flow cytometry and T cell IL-2 and IFN-γ gene expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in activated canine T cells incubated with cyclosporine and dexamethasone in vitro. For flow cytometric assays, diluted whole blood was cultured for 7 h in the presence of cyclosporine (10, 100, 500, and 1000 ng/mL) or dexamethasone (10 ng/mL, 100 ng/mL, 1 µg/mL, and 10 µg/mL). For qRT-PCR, whole blood was cultured for 5 h with the same drugs at the same concentrations, and RNA was then extracted from leukocytes. Flow cytometry and qRT-PCR both demonstrated inhibition of IL-2 and IFN-γ that was concentration-dependent in response to cyclosporine, and was more variable for dexamethasone. Quantitative RT-PCR but not flow cytometry documented significant reduction of IL-2 expression after dexamethasone treatment, while both methods showed concentration-dependent suppression of IFN-γ. Quantitative RT-PCR also revealed additional cytokine suppression at higher cyclosporine concentrations, an effect not found using flow cytometry, and may therefore be the preferred method for cytokine determination in dogs. Suppression of IL-2 and IFN-γ in activated T cells may have potential as an indicator of the efficacy of cyclosporine and glucocorticoids in suppressing canine T cell function in vivo, and may therefore be of value for characterizing the immunosuppression induced by these drugs in clinical patients.


Assuntos
Ciclosporina/farmacologia , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Linfócitos T/efeitos dos fármacos , Animais , Ciclosporina/administração & dosagem , Dexametasona/administração & dosagem , Cães , Relação Dose-Resposta a Droga , Glucocorticoides/farmacologia , Imunidade Celular/efeitos dos fármacos , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Interferon gama/genética , Interleucina-2/genética
12.
Life Sci ; 233: 116750, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31408659

RESUMO

AIM: Rheumatoid arthritis (RA) is the most widespread inflammatory arthropathy, which causes severe disability. It is highly important to ameliorate the side effects caused by different drugs used to treat RA. Therefore, this study assessed the potential role of ß-caryophyllene (BCP) in treating adjuvant-induced arthritis (AIA), increasing the efficacy of methotrexate (MTX) and/or leflunomide (LEF), and ameliorating their side effects. MATERIAL AND METHODS: AIA was induced in rats by injecting complete Freund's adjuvant. The rats were divided into different groups such as sham group; control group; monotherapy groups, including BCP (300 mg/kg), MTX (1 mg/kg), and LEF (10 mg/kg); and combined groups, including MTX + BCP, LEF + BCP, MTX + LEF, and MTX + LEF + BCP groups. KEY FINDINGS: Monotherapy with BCP or MTX or LEF as well as MTX + LEF significantly reduced paw thickness and arthritic index; the histopathological changes in hind paw joints were recovered; and oxidative stress and tumor necrosis factor-alpha (TNF-α) levels in arthritic rats were reduced. The co-administration of BCP and MTX and/or LEF significantly improved the therapeutic efficacy of MTX and/or LEF and significantly reduced the myelosuppressive and hepatotoxic effects of MTX and/or LEF. Taken together, BCP could be used with MTX and/or LEF for the treatment of RA to reduce the side effects of the drugs and increase their efficacy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Artrite Experimental/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Imunossupressores/administração & dosagem , Leflunomida/administração & dosagem , Metotrexato/administração & dosagem , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antimetabólitos Antineoplásicos/efeitos adversos , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Quimioterapia Combinada , Imunossupressores/efeitos adversos , Leflunomida/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Ratos , Ratos Wistar , Sesquiterpenos/administração & dosagem
13.
Transplant Proc ; 51(6): 1758-1762, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399163

RESUMO

BACKGROUND: Although tacrolimus is an effective immunosuppressive drug used for preventing biopsy proven acute rejection (BPAR) in kidney transplanted patients, its nephrotoxicity may compromise renal function and lead to delayed initiation because of its side effects. This study aimed to evaluate the safety of early initiation of tacrolimus in the occurrence of BPAR during the first 90 days post transplant. METHODS: We conducted a retrospective cohort study involving 315 patients who underwent kidney transplantation from 2015 to 2017. Comparisons were performed between 2 groups according to whether the start time of tacrolimus therapy was delayed or not delayed. Cox proportional hazards models were used to examine the association between variables and the occurrence of BPAR. RESULTS: The incidence of BPAR was 14.9% (n = 47) and it was significantly higher in the delayed group (19.4% vs 6.4%; P = .002). Delayed initiation tacrolimus group was significantly associated with the risk of BPAR (hazard ratio: 2.95; P < .036). The overall mortality rate was 2.5% (n = 8) and there was no association between delayed initiation therapy and death (P = .56). CONCLUSION: Our study confirmed that delayed initiation of tacrolimus in patients with delayed graft function is associated with a high risk of BPAR.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Tacrolimo/administração & dosagem , Tempo para o Tratamento , Adulto , Estudos de Coortes , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Incidência , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Int J Nanomedicine ; 14: 5849-5863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440050

RESUMO

Background: Topical application of tacrolimus (FK506) was effective in treating atopic dermatitis (AD); however, the therapeutic efficiency is hampered by its poor penetration into the skin and local side effects of transient irritation symptoms with a burning sensation, a feeling of warmth or heat. Menthol and camphor have been widely used in topical compound formulations for adjunctive pharmacotherapy for antipruritics and analgesics owing to their cool nature, and both present skin penetration enhancing effects. Moreover, they can form a liquid eutectic oil to solubilize hydrophobic drugs. Purpose: Taking advantages of menthol/camphor eutectic (MCE), this work aims to integrate FK506 into MCE to construct a microemulsion system, i.e., FK506 MCE ME, which simultaneously enhances the percutaneous delivery and treatment efficacy, while reduces the side effects of FK506. Methods: The formulation of FK506 MCE ME was optimized and characterized. Different formulations containing FK506 were topically administered to treat 1-chloro-2, 4-dinitrobenzene (DNCB)-induced murine AD. Results: MCE solubilized FK506. FK506 in MCE ME penetrated skin in vitro more than in the commercial ointment, and MCE predominantly exerted the enhancing effects in MCE ME. FK506 MCE ME or FK506 MCE ME gel had greater effects on clinical symptoms, histological analysis, and IgE than did commercial FK506. The anti-pruritic and down-regulation of substance P effects of MCE ME vehicle mitigated the side effects of FK506 application. Conclusion: MCE ME presented the excellent properties of simultaneously enhancing the percutaneous delivery and treatment efficacy, while reducing the side effects of FK506 for AD. Therefore, MCE ME is a promising nanoscale system for FK506 to effectively treating AD with low irritation and high medication adherence. Chemical compounds studied in this article: Tacrolimus (PubChem CID: 445643); menthol (PubChem CID: 1254); camphor (PubChem CID: 2537).


Assuntos
Dermatite Atópica/tratamento farmacológico , Emulsões/química , Óleos/química , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Administração Cutânea , Animais , Cânfora/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dermatite Atópica/induzido quimicamente , Regulação para Baixo/efeitos dos fármacos , Orelha/patologia , Humanos , Imunoglobulina E/sangue , Imunossupressores/administração & dosagem , Masculino , Mentol/química , Camundongos , Camundongos Endogâmicos BALB C , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Baço/efeitos dos fármacos , Substância P/metabolismo , Tacrolimo/administração & dosagem , Tacrolimo/farmacologia , Resultado do Tratamento , Perda Insensível de Água/efeitos dos fármacos
15.
Medicine (Baltimore) ; 98(34): e15415, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441835

RESUMO

BACKGROUND: Multiple sclerosis is the most common demyelinating disease of the central nervous system with serious social and economic burden. Siponimod is a sphingosine-1-phosphate receptor agonist, and clinical trials in the past decade have shown good prospects for the treatment of multiple sclerosis. But there is a lack of comprehensive understanding of the dose-effect relationship and safety in different subtypes of multiple sclerosis at present. METHODS: We will perform a systematic review and meta-analysis of clinical randomized controlled trials to evaluate the efficacy and safety of siponimod in multiple sclerosis. We will search PubMed, EMBASE, Cochrane Library, Clinical Trials, Cochrane Central Register of Controlled Trials (CENTRAL) using a comprehensive strategy. The reference lists of the articles we select for inclusion will be checked to identify additional studies for potential inclusion. Two reviewers will review all literature independently. Upon inclusion of articles, another 2 reviewers will extract available data using a standardized form and assess the potential bias. Review Manager will be used to conduct data synthesis. There is no requirement of ethical approval and informed consent. RESULT: This is the first systematic assessment of siponimod for the treatment of multiple sclerosis. We predict it will provide high-quality synthesis of existing evidence for the efficacy and safety of siponimod for multiple sclerosis and a relatively comprehensive reference for clinical practice and clinical trials about siponimod to be conducted. CONCLUSION: The results of the systematic review and meta-analysis will provide updated evidence for the use of siponimod for multiple sclerosis. REGISTRATION: The systematic review and meta-analysis is registered in the PROSPERO international prospective register of systematic review (PROSPERO#CRD42018112721).


Assuntos
Azetidinas/uso terapêutico , Compostos de Benzil/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Compostos de Benzil/administração & dosagem , Compostos de Benzil/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Esclerose Múltipla/classificação , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
16.
Biomater Sci ; 7(9): 3729-3740, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31403142

RESUMO

Targeted delivery of immunosuppressants to allografts can increase the concentrations of drugs in pathological tissues, improve therapeutic effects and reduce unfavorable side effects. Therefore, we synthesized FK506-loaded microbubbles (FK506-MBs) for site-specific release of FK506 into transplanted hearts by the ultrasound-targeted microbubble destruction (UTMD) technique. The average particle size of FK506-MBs was 1.65 ± 0.32 µm and they had high drug loading and encapsulation efficiency. The in vivo drug concentration in transplanted hearts that were treated with FK506-MBs plus UTMD was about 1.64-fold higher than that in grafts that received free FK506 at the same dosage. The degree of graft rejection in the FK506-MB plus UTMD group was lower than those of other groups. Both infiltration of T cells and secretion of inflammatory cytokines were significantly reduced in the FK506-MB plus UTMD group. More importantly, the mean survival time of the grafts was significantly longer (16.00 ± 0.89 day) than those of the PBS group (6.66 ± 1.36 day) and the FK506 group (12.83 ± 1.17 day). In addition, we also found that the concentration of FK506 in whole blood was lower in the FK506-MB plus UTMD group than that in the FK506 group, which would be beneficial for reducing the side effects. Hence, our results showed that combining FK506-MBs with UTMD was an effective strategy to deliver FK506 to transplanted hearts, which can increase the local drug concentration and enhance its efficacy on rejection. Ultrasound-targeted drug release is safe and radiation-free, with great potential for clinical transformation, and could also be extended to the treatment of other graft rejection cases, such as liver transplantation, kidney transplantation and so on.


Assuntos
Portadores de Fármacos/química , Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração , Imunossupressores/farmacocinética , Miocárdio/metabolismo , Tacrolimo/farmacocinética , Animais , Liberação Controlada de Fármacos , Estudos de Viabilidade , Imunossupressores/administração & dosagem , Masculino , Microbolhas , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Ratos , Tacrolimo/administração & dosagem , Ultrassonografia
17.
Transplant Proc ; 51(6): 1848-1852, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256869

RESUMO

The incidence rate of breast fibroadenomas is higher among female kidney transplant (KT) patients treated using cyclosporine (CsA) for immunosuppression than in the general population. As such, there is an effort to convert immunosuppression from CsA or tacrolimus to sirolimus. Our aim was to assess the reversibility of a breast fibroadenoma after conversion in a small cohort of female KT recipients. This was an open-label, single-arm study including 128 female KT recipients, with a positive finding of a breast fibroadenoma in 15. Lesions were classified according to the Breast Imaging Reporting and Data System (BIRADS). Among these 15, a total of 7 converted from tacrolimus to sirolimus and 8 converted from CsA. We measured the change in BIRADS category and hormone and cytokine levels from baseline to 12 months after conversion. The primary outcome was progression or reversal of existing fibroadenomas at 12 months after conversion. Secondary outcomes were differences in hormone and cytokine levels. Conversion from CsA or tacrolimus to sirolimus had no significant effect on the BIRADS classification. However, conversion to sirolimus did produce a significant decrease in the level of transforming growth factor ß cytokine, this level being closely associated with fibroadenomas. Conversion from a calcineurin inhibitor to sirolimus can block the progression of fibroadenomas. Further research is needed to confirm our results.


Assuntos
Neoplasias da Mama/induzido quimicamente , Inibidores de Calcineurina/efeitos adversos , Fibroadenoma/induzido quimicamente , Imunossupressores/administração & dosagem , Complicações Pós-Operatórias/induzido quimicamente , Sirolimo/administração & dosagem , Adulto , Neoplasias da Mama/epidemiologia , Ciclosporina/efeitos adversos , Substituição de Medicamentos/métodos , Feminino , Fibroadenoma/epidemiologia , Rejeição de Enxerto , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Imunossupressores/efeitos adversos , Incidência , Transplante de Rim/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Tacrolimo/efeitos adversos
19.
Metas enferm ; 22(6): 5-11, jul. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-184042

RESUMO

Objetivo: determinar la evolución de la tasa de vacunación antigripal y antineumocócica (23 valencias) entre los años 2010 y 2014 en pacientes reumáticos en tratamiento con inmunosupresores y evaluar la magnitud de infecciones respiratorias documentadas en el año posterior a la vacunación. Método: estudio descriptivo longitudinal retrospectivo. Se reclutaron por conveniencia 200 pacientes con artritis reumatoide o espondiloartropatías en tratamiento con fármacos antirreumáticos modificadores de la enfermedad (FAME) sintético, FAME biológico o corticoides. Se conformaron dos grupos de 100 pacientes (2010 y 2014) en los que se revisaron historias clínicas para recoger variables demográficas, comorbilidades, hábitos tóxicos, diagnóstico reumatológico y años de evolución de este, tratamiento, administración de la vacuna antigripal y antineumocócica 23v y número de infecciones respiratorias en el año posterior. Resultados: en la muestra un 66% fue mujer, la edad media fue de 66 años y 12 de evolución de la enfermedad. El 43,5% había recibido vacunación antigripal y el 30% vacunación neumocócica 23v. El 21,5% presentó infección respiratoria en el tiempo de seguimiento. Hubo una mayor tasa de vacunación antigripal y antineumocócica en 2014 frente a 2010 (49 y 29% vs. 38% y 21%, respectivamente), siendo solo estadísticamente significativo el aumento en la cobertura antineumocócica. Los pacientes mayores de 65 años y alguna comorbilidad o hábito tóxico son más vacunados (p< 0,05). No hubo diferencias en las vacunaciones ni en el número de infecciones respiratorias, ni en función del diagnóstico reumatológico, ni del tratamiento recibido por el paciente. Conclusiones: la tasa de vacunación mejoró en 2014 respecto a 2010. No obstante, el profesional enfermero ha de intervenir en mejorar la tasa de vacunación en estos pacientes


Objective: to determine the evolution in the rate of influenza and pneumococcal (23-valent) vaccination between the years 2010 and 2014 in rheumatic patients on treatment with immunosuppressants, and to evaluate the extent of documented respiratory infections within the year after vaccination. Method: a retrospective cross-sectional descriptive study. Two hundred (200) patients were recruited by convenience sampling, with rheumatoid arthritis or spondyloarthropathy, on treatment with synthetic disease modifying antirheumatic drugs (DMARDs), biologic DMARDs or corticosteroids. Two arms of 100 patients were formed (2010 and 2014), and clinical records were reviewed in order to collect demographical variables, comorbidities, toxic habits, rheumatology diagnosis and years of disease evolution, treatment, administration of the influenza and the pneumococcal 23 vaccine, and number of respiratory infections during the following year. Results: in the sample, 66% were women, their mean age was 66 years, with 12 years of disease evolution; 43.5% had received influenza vaccination, and 30% pneumococcal 23v vaccination; 21.5% presented respiratory infection within the time of follow-up. There was a higher rate of influenza and pneumococcal vaccination in 2014 vs. 2010 (49 and 29% vs. 38% and 21%, respectively); only the increase in pneumococcal coverage was statistically significant. Patients >65-year-old and with some comorbidity or toxic habit were more vaccinated (p< 0.05). There were no differences in vaccinations or in the number of respiratory infections based on the rheumatology diagnosis or the treatment received by the patient. Conclusions: the vaccination rate improved in 2014 vs. 2010. However, the nursing professional must be involved in the improvement of the vaccination rate for these patients


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Vacinas contra Influenza/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia , Imunossupressores/administração & dosagem , Cobertura Vacinal , Estudos Transversais , Estudos Longitudinais , Estudos Retrospectivos , Prednisona
20.
BMC Infect Dis ; 19(1): 664, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349802

RESUMO

BACKGROUND: Several studies have identified predictors of severe infections in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). However, the development of oral candidiasis (OC) as a predictor of subsequent severe infections has not been evaluated. The aim of this study was to assess the association between OC and subsequent severe infection requiring hospitalization during immunosuppressive therapy in AAV. METHODS: This single-center retrospective cohort study included 71 consecutive patients with newly diagnosed AAV from Aichi Medical University Hospital, Japan, starting immunosuppressive therapy between March 2013 and December 2018. The relationships between OC and subsequent severe infections were assessed using multivariate Cox proportional hazards models, adjusted for clinically relevant factors. RESULTS: During the follow-up period (median, 23 months; interquartile range, 11-51 months), 25 severe infectious episodes occurred in 19 patients (26.8%) and OC occurred in 17 patients (23.9%). A log-rank test showed that the OC group was significantly associated with severe infection (P <  0.001). Multivariate Cox proportional hazards models identified lower serum albumin (per 1 g/dl adjusted hazard ratio (HR)  = 0.38, 95% confidence interval (CI): 0.15-0.85; P  =  0.018), use of methylprednisolone pulse (adjusted HR  =  5.44, 95% CI: 1.54-20.0; P  =  0.010), and OC (adjusted HR  = 5.31, 95% CI: 1.86-15.8; P  =  0.002) as significant predictors of severe infection. Furthermore, a significant effect modification of the use of methylprednisolone pulse on OC was observed (P <  0.001). CONCLUSIONS: OC is one of the predictors of subsequent severe infections. The results suggest the importance of prolonging infection surveillance, especially for patients who developed OC under strong immunosuppressive therapy.


Assuntos
Candidíase Bucal/etiologia , Imunossupressores/efeitos adversos , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Feminino , Seguimentos , Humanos , Imunossupressão , Imunossupressores/administração & dosagem , Japão , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos
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