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[PMID]:29465551
[Au] Autor:Wang KL; Ma SF; Pang LY; Zhang MN; Hu LY; Liu MJ; Zou LP
[Ad] Endereço:Department of Pediatrics, Chinese PLA General Hospital, Beijing, China.
[Ti] Título:Sirolimus alternative to blood transfusion as a life saver in blue rubber bleb nevus syndrome: A case report.
[So] Source:Medicine (Baltimore);97(8):e9453, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterized by multiple venous malformations. The gastrointestinal bleeding and secondary iron deficiency anemia are the most common complications. There are currently no effective treatments for BRBNS. Here, we report a case of successful treatment with a small dose of sirolimus of a BRBN patient with a de novo gene mutation. PATIENT CONCERNS: A 12-year-old female was admitted to our hospital with multiple hemangiomas for 12 years. The patient often displayed melena; she recently received transfusion of 2 units of red blood cells once every 2 weeks. Multiple fist-sized hemangiomas were piled up on both sides and back of the neck, and were also noted on the arms, legs, chest, back, and on the tip of the tongue. The laboratory findings demonstrated severe anemia. Blood sample sequencing detected a heterozygous de novo mutation c.2545C > Tin the TEK gene. DIAGNOSES: Based on these findings, final diagnosis of Blue rubber bleb nevus syndrome (BRBNS) was made. INTERVENTIONS: After the diagnosis, low-dose sirolimus was orally administered. OUTCOMES: The patient's hemoglobin was increased after treatment with sirolimus for 1 month. Since the initial treatment with sirolimus, she had not received any blood transfusions. The skin and mucosal hemangioma decreased significantly, and new digestive tract hemorrhage, muscle hematoma, or adverse drug reactions were not observed. LESSONS: we report a case of a mutation in exon 15 of the TEK gene leading to BRBN. It was successfully treated with a small dose of sirolimus as an alternative to blood transfusion in order to save the of BRBN patient's life.
[Mh] Termos MeSH primário: Neoplasias Gastrointestinais/tratamento farmacológico
Imunossupressores/administração & dosagem
Nevo Azul/tratamento farmacológico
Sirolimo/administração & dosagem
Neoplasias Cutâneas/tratamento farmacológico
[Mh] Termos MeSH secundário: Transfusão de Sangue
Criança
Feminino
Neoplasias Gastrointestinais/diagnóstico
Neoplasias Gastrointestinais/genética
Seres Humanos
Mutação
Nevo Azul/diagnóstico
Nevo Azul/genética
Neoplasias Cutâneas/diagnóstico
Neoplasias Cutâneas/genética
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunosuppressive Agents); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180222
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009453


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[PMID]:29442004
[Au] Autor:Wang Y; Li X; He Z; Chen W; Lu J
[Ti] Título:Rapamycin attenuates palmitate-induced lipid aggregation by up-regulating sirt-1 signaling in AML12 hepatocytes.
[So] Source:Pharmazie;71(12):733-737, 2016 12 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Rapamycin (Rap), a specific inhibitor of the mTOR signaling, has been shown to affect lipid metabolism in vitro and in vivo. Sirt-1, an NAD+ dependent deacetylase, regulates a variety of cellular processes, including aging, lifespan extension and glucose and lipid metabolism. Herein, we applied a cellular steatosis model to investigate whether rapamycin's role in lipid metabolism is sirt 1-associated. Cells were exposed to palmitate stimulation for 48 h with or without rapamycin treatment. Lipid droplets in AML12 cells were observed by oil red O staining, and the intracellular lipid content was measured. We found that rapamycin treatment, at a relatively low concentration, significantly attenuated lipid aggregation, whereas knockdown of sirt-1 by siRNA abrogated rapamycin's effect on ameliorating lipid accumulation. Moreover, rapamycin exposure increased the expression levels of sirt-1 and AMPK, and enhanced sirt-1 deacetylase activity in steatotic AML12 hepatocytes. This is the first report demonstrating that rapamycin ameliorates lipid accumulation through upregulating sirt-1 signaling supporting the hypothesis that rapamycin may positively influence sirt-1 signaling in maintaining metabolic homeostasis.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/farmacologia
Hepatócitos/efeitos dos fármacos
Hepatócitos/metabolismo
Metabolismo dos Lipídeos/efeitos dos fármacos
Palmitatos/antagonistas & inibidores
Sirolimo/farmacologia
Sirtuína 1/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Camundongos
Proteínas Quinases Ativadas por Mitógeno/biossíntese
Palmitatos/farmacologia
RNA Interferente Pequeno/farmacologia
Transdução de Sinais/efeitos dos fármacos
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Palmitates); 0 (RNA, Small Interfering); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.5.1.- (Sirt1 protein, mouse); EC 3.5.1.- (Sirtuin 1); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6695


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[PMID]:28469097
[Au] Autor:Yi YH; Yang Z; Han YW; Huai J
[Ad] Endereço:Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
[Ti] Título:Effects of Rapamycin on Clinical Manifestations and Blood Lipid Parameters in Different Preeclampsia-like Mouse Models.
[So] Source:Chin Med J (Engl);130(9):1033-1041, 2017 May 05.
[Is] ISSN:0366-6999
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The pathogenesis of some types of preeclampsia is related to fatty acid oxidation disorders. Rapamycin can regulate fatty acid metabolism. This study aimed to investigate the effects of rapamycin on the clinical manifestations and blood lipid parameters in different preeclampsia-like mouse models. METHODS: Two preeclampsia-like mouse models and a control group were established: L-NA (injected with Nω-nitro-L-arginine methyl ester), LPS (injected with lipopolysaccharide), and the control group with normal saline (NS). The mouse models were established at preimplantation (PI), early- and late-pregnancy (EP, LP) according to the time of pregnancy. The administration of rapamycin (RA; L-NA+RA, LPS+RA, and NS+RA) or vehicle as controls (C; L-NA+C, LPS+C, NS+C) were followed on the 2nd day after the mouse models' establishment. Each subgroup consisted of eight pregnant mice. The mean arterial pressure (MAP), 24-h urinary protein, blood lipid, fetus, and placental weight were measured. The histopathological changes and lipid deposition of the liver and placenta were observed. Student's t-test was used for comparing two groups. Repeated measures analysis of variance was used for blood pressure analysis. Qualitative data were compared by Chi-square test. RESULTS: The MAP and 24-h urinary protein in the PI, EP, and LP subgroups of the L-NA+C and LPS+C groups were significantly higher compared with the respective variables in the NS+C group (P < 0.05). The preeclampsia-like mouse models were established successfully. There was no significant difference in the MAP between the PI, EP, and LP subgroups of the L-NA+RA and L-NA+C groups and the LPS+RA and LPS+C groups. The 24-h urine protein levels in the PI and EP subgroups of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C groups (1037 ± 63 vs. 2127 ± 593 µg; 976 ± 42 vs. 1238 ± 72 µg; bothP < 0.05), also this effect appeared similar in the PI and EP subgroups of the LPS+RA and LPS+C groups (1022 ± 246 vs. 2141 ± 432 µg; 951 ± 41 vs. 1308 ± 30 µg; bothP < 0.05). The levels of serum-free fatty acid (FFA) in the PI and EP subgroups of the L-NA+RA groups were significantly lower compared with the respective levels in the L-NA+C group (2.49 ± 0.44 vs. 3.30 ± 0.18 mEq/L; 2.23 ± 0.29 vs. 2.84 ± 0.14 mEq/L; bothP < 0.05). The levels of triglycerides (TG) and total cholesterol in the PI subgroup of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C (1.51 ± 0.16 vs. 2.41 ± 0.37 mmol/L; 2.11 ± 0.17 vs. 2.47 ± 0.26 mmol/L; bothP < 0.05), whereas high-density lipoprotein serum concentration was significantly higher (1.22 ± 0.19 vs. 0.87 ± 0.15 mmol/L;P < 0.05) and low-density lipoprotein serum concentration did not exhibit a significant difference. There were no significant differences in the FFA of the PI, EP, and LP subgroups between the LPS+RA and the LPS+C groups. The levels of TG in the PI subgroup of the LPS+RA group were significantly lower compared with the respective levels in the LPS+C group (0.97 ± 0.05 vs. 1.22 ± 0.08 mmol/L;P < 0.05). CONCLUSION: Rapamycin can improve clinical manifestations and blood lipid profile in part of the preeclampsia-like mouse models.
[Mh] Termos MeSH primário: Lipídeos/sangue
Pré-Eclâmpsia/sangue
Pré-Eclâmpsia/tratamento farmacológico
Sirolimo/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Pressão Sanguínea/efeitos dos fármacos
Distribuição de Qui-Quadrado
Colesterol/sangue
Modelos Animais de Doenças
Feminino
Metabolismo dos Lipídeos/efeitos dos fármacos
Lipoproteínas HDL/sangue
Lipoproteínas LDL/sangue
Camundongos
Camundongos Endogâmicos C57BL
Placenta/efeitos dos fármacos
Placenta/metabolismo
Gravidez
Resultado da Gravidez
Triglicerídeos/administração & dosagem
Triglicerídeos/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipids); 0 (Lipoproteins, HDL); 0 (Lipoproteins, LDL); 0 (Triglycerides); 97C5T2UQ7J (Cholesterol); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.4103/0366-6999.204924


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[PMID]:29208258
[Au] Autor:Martirossian A; Shah S; Carrete L; Valle J; Valentine V
[Ad] Endereço:Department of Internal Medicine (AM, LC), University of Texas Medical Branch, Galveston, Texas; Department of Internal Medicine, Division of Pulmonary Critical Care & Sleep Medicine (SS, JV), University of Texas Medical Branch, Galveston, Texas; Department of Internal Medicine, Division of Pulmo
[Ti] Título:Durability of Sirolimus for Lymphangioleiomyomatosis.
[So] Source:Am J Med Sci;354(6):603-607, 2017 12.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lymphangioleiomyomatosis (LAM), a rare, multisystem disorder primarily affecting women of reproductive age, is characterized by cystic-appearing lung lesions, progressive loss of lung function, chylous effusions and renal angiomyolipomas. Sirolimus, an mammalian target of rapamycin inhibitor, has been shown to stabilize lung function, reduce symptoms and resolve chylous effusions in the short term for patients with LAM. Herein, we report a premenopausal female with LAM who experienced complete and durable resolution of her chylothoraces with significant and sustained improvement in lung function on sirolimus.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/uso terapêutico
Neoplasias Pulmonares/tratamento farmacológico
Linfangioleiomiomatose/tratamento farmacológico
Sirolimo/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Neoplasias Pulmonares/complicações
Neoplasias Pulmonares/diagnóstico por imagem
Linfangioleiomiomatose/complicações
Linfangioleiomiomatose/diagnóstico por imagem
Imagem por Ressonância Magnética
Derrame Pleural/etiologia
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE


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[PMID]:29241733
[Au] Autor:Zhang B; Cui Y; Wang L; Zhao L; Hou C; Zeng Q; Zhang Z; Yu J; Zhao Y; Nie J; Chen X; Wang A; Liu H
[Ad] Endereço:School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.
[Ti] Título:Autophagy regulates high concentrations of iodide-induced apoptosis in SH-SY5Y cells.
[So] Source:Toxicol Lett;284:129-135, 2018 Mar 01.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:To date, there are many people residing in areas with high levels of iodide in water. Our previous epidemiological study showed that exposure to high iodine in drinking water significantly reduced the intelligence of children although the mechanisms remain unclear. To explore whether high concentrations of iodide may cause cytotoxic effect and the role of autophagy in the high iodide-induced apoptosis, human neuroblastoma cells (SH-SY5Y cells) were exposed to high concentrations of iodide. Morphological phenotypes, cell viability, Hoechst 33258 staining, the expression levels of apoptosis and autophagy-related proteins were detected. A possible effect of an inhibitor (3-methyladenine, 3-MA) or an inducer (rapamycin) of autophagy on high iodide-induced apoptosis also was examined. Results indicated that high iodide changed cellular morphology, decreased cell viability and increased the protein's expression level of apoptosis and autophagy. In addition, high iodide-induced apoptosis was enhanced by inhibition of autophagy and inhibited by activation of autophagy in SH-SY5Y cells. Collectively, high concentrations of iodide are toxic to SH-SY5Y cells, as well as induce apoptosis and autophagy. Furthermore, autophagy plays a regulatory role in high concentrations of iodide-induced apoptosis in SH-SY5Y cells.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Autofagia/efeitos dos fármacos
Iodetos/toxicidade
[Mh] Termos MeSH secundário: Contagem de Células
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Microscopia de Fluorescência
Sirolimo/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Iodides); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


  6 / 16176 MEDLINE  
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[PMID]:29177545
[Au] Autor:Gu Y; Zhou Y; Shi X; Xin Y; Shan Y; Chen C; Cao T; Fang W; Li X
[Ad] Endereço:Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou, 310058, China.
[Ti] Título:Porcine teschovirus 2 induces an incomplete autophagic response in PK-15 cells.
[So] Source:Arch Virol;163(3):623-632, 2018 Mar.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Autophagy is a homeostatic process that has been shown to be vital in the innate immune defense against pathogens. However, little is known about the regulatory role of autophagy in porcine teschovirus 2 (PTV-2) replication. In this study, we found that PTV-2 infection induces a strong increase in GFP-LC3 punctae and endogenous LC3 lipidation. However, PTV-2 infection did not enhance autophagic protein degradation. When cellular autophagy was pharmacologically inhibited by wortmannin or 3-methyladenine, PTV-2 replication increased. The increase in virus yield via autophagy inhibition was further confirmed by silencing atg5, which is required for autophagy. Furthermore, PTV-2 replication was suppressed when autophagy was activated by rapamycin. Together, the results suggest that PTV-2 infection activates incomplete autophagy and that autophagy then inhibits further PTV-2 replication.
[Mh] Termos MeSH primário: Proteína 5 Relacionada à Autofagia/antagonistas & inibidores
Autofagia/efeitos dos fármacos
Células Epiteliais/virologia
Interações Hospedeiro-Patógeno
Teschovirus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adenina/análogos & derivados
Adenina/farmacologia
Androstadienos/farmacologia
Animais
Autofagia/genética
Proteína 5 Relacionada à Autofagia/genética
Proteína 5 Relacionada à Autofagia/metabolismo
Linhagem Celular
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/metabolismo
Regulação da Expressão Gênica
Genes Reporter
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Rim
Proteínas Associadas aos Microtúbulos/genética
Proteínas Associadas aos Microtúbulos/metabolismo
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Transdução de Sinais
Sirolimo/farmacologia
Suínos
Teschovirus/genética
Teschovirus/crescimento & desenvolvimento
Teschovirus/metabolismo
Replicação Viral/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstadienes); 0 (Autophagy-Related Protein 5); 0 (Microtubule-Associated Proteins); 0 (RNA, Small Interfering); 147336-22-9 (Green Fluorescent Proteins); 5142-23-4 (3-methyladenine); JAC85A2161 (Adenine); W36ZG6FT64 (Sirolimus); XVA4O219QW (wortmannin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3652-2


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[PMID]:29390423
[Au] Autor:Amodeo I; Colnaghi M; Raffaeli G; Cavallaro G; Ciralli F; Gangi S; Leva E; Pignataro L; Borzani I; Pugni L; Mosca F
[Ad] Endereço:Neonatal Intensive Care Unit.
[Ti] Título:The use of sirolimus in the treatment of giant cystic lymphangioma: Four case reports and update of medical therapy.
[So] Source:Medicine (Baltimore);96(51):e8871, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Lymphatic malformations (LMs) are rare and benign anomalies resulting from the defective embryological development of the primordial lymphatic structures. Due to their permeative growth throughout all tissue layers, treatment is often challenging. Small asymptomatic lesions can be conservatively managed, while symptomatic lesions require active management. Surgery has been historically considered the treatment of choice, but today less invasive therapeutic options are preferred (sclerotherapy, laser therapy, oral medications). However, there are not uniform therapeutic protocols. Sirolimus is an oral medication that has been reported to be effective in the recent literature. Here we present the case of 4 newborns with giant multicystic lymphangioma treated with oral sirolimus after surgical resection had failed. PATIENT CONCERNS: At birth the LMs were clinically appreciated as giant masses involving different organs and structures. DIAGNOSES: All patients had a prenatal diagnosis of giant multicystic lymphangioma confirmed at histological and cytological analysis. INTERVENTIONS: Patients were treated with oral sirolimus after unsuccessful surgical resection. OUTCOMES: In all patients, sirolimus determined an overall reduction of the mass and a global involution from the macro- to the microcystic composition. Sirolimus was safe and poor disadvantages had been observed. The main and isolated adverse effect at laboratory analysis was progressive dyslipidemia, with increasing levels of total cholesterol and triglycerides. LESSONS: To date, our experience with sirolimus in the management of LMs is favorable. We recommend the use of sirolimus after unsuccessful surgical excision have been tried or when the surgical approach is not feasible. A multidisciplinary follow-up is needed to monitor disease evolution.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/uso terapêutico
Linfangioma Cístico/diagnóstico
Sirolimo/uso terapêutico
[Mh] Termos MeSH secundário: Administração Oral
Antibióticos Antineoplásicos/administração & dosagem
Diagnóstico Diferencial
Feminino
Seres Humanos
Recém-Nascido
Linfangioma Cístico/diagnóstico por imagem
Linfangioma Cístico/tratamento farmacológico
Imagem por Ressonância Magnética
Masculino
Sirolimo/administração & dosagem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008871


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[PMID]:28461109
[Au] Autor:Amrouche K; Jamin C
[Ad] Endereço:UMR 1227, Lymphocytes B et Autoimmunité, Université de Brest, INSERM, Brest, France; LabEx IGO "Immunotherapy, Graft, Oncology", Brest, France.
[Ti] Título:Influence of drug molecules on regulatory B cells.
[So] Source:Clin Immunol;184:1-10, 2017 11.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:By their suppressive functions, regulatory B (Breg) cells are considered as key elements in the control and development of various disease states. Many signals can induce Bregs in vivo and in vitro and often from heterogeneous populations. Several specific signals delivered in a timely immunological context contribute to the establishment of Bregs. These are endogenous and physiological signals or stimuli, widely discussed in the literature participating in the establishment of an effective immune response. However, exogenous signals, much less clearly identified can also be considered as Bregs inducers. These extrinsic signals are capable of directly or indirectly influencing the suppressive capacity of Bregs, but also their expansion and functional restoration in its absence. Faced with the excitement generated by the development of processes favoring the expansion of Bregs in mice for therapeutic purposes, the challenge today is to extrapolate such approaches in humans. This perspective may already be in effect.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Linfócitos B Reguladores/efeitos dos fármacos
Imunossupressores/farmacologia
Vitaminas/farmacologia
[Mh] Termos MeSH secundário: Corticosteroides/farmacologia
Animais
Anticorpos Monoclonais Humanizados/farmacologia
Fator Ativador de Células B/imunologia
Linfócitos B Reguladores/imunologia
Antígenos CD40/imunologia
Citocinas/imunologia
Seres Humanos
Metotrexato/farmacologia
Ácido Micofenólico/farmacologia
Pirróis/farmacologia
Quinazolinas/farmacologia
Receptores de Antígenos de Linfócitos B/imunologia
Semaforinas/farmacologia
Sirolimo/farmacologia
Receptores Toll-Like/imunologia
Tretinoína/farmacologia
Vitamina D/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents); 0 (B-Cell Activating Factor); 0 (CD40 Antigens); 0 (Cytokines); 0 (Immunosuppressive Agents); 0 (Pyrroles); 0 (Quinazolines); 0 (Receptors, Antigen, B-Cell); 0 (Semaphorins); 0 (Toll-Like Receptors); 0 (Vitamins); 1406-16-2 (Vitamin D); 5688UTC01R (Tretinoin); 7I279E1NZ8 (sotrastaurin); HU9DX48N0T (Mycophenolic Acid); I031V2H011 (tocilizumab); W36ZG6FT64 (Sirolimus); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  9 / 16176 MEDLINE  
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[PMID]:29269724
[Au] Autor:Rashid-Farokhi F; Afshar H
[Ad] Endereço:Chronic Kidney Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
[Ti] Título:Lymphedema of the Transplanted Kidney and Abdominal Wall with Ipsilateral Pleural Effusion Following Kidney Biopsy in a Patient Treated with Sirolimus: A Case Report and Review of the Literature.
[So] Source:Am J Case Rep;18:1370-1376, 2017 Dec 22.
[Is] ISSN:1941-5923
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor, which is used in immunosuppressive treatment regimens in organ transplant recipients. Although mTOR inhibitors are well tolerated, their adverse effects have been reported. Sirolimus treatment in transplant recipients has been reported to be associated with lymphedema of the skin and subcutaneous tissues, and with pleural effusion, but edema of internal organs and organomegaly have not been previously reported. A case is presented lymphedema of the transplanted kidney and abdominal wall with ipsilateral pleural effusion following kidney biopsy in a patient treated with sirolimus. CASE REPORT A 32-year-old woman with a history of end-stage renal disease of unknown etiology had undergone right renal transplantation from an unrelated living donor, eight years previously. She was referred to our hospital with dyspnea, localized abdominal pain, and swelling of the transplanted kidney. The symptoms appeared following a kidney biopsy and the replacement of cyclosporin with sirolimus four months previously. On examination, she had localized swelling of the abdominal wall overlying the transplanted kidney, and a right pleural effusion. Hydronephrosis and nephrotic syndrome were excluded as causes of kidney enlargement. Following the withdrawal of sirolimus therapy her symptoms resolved within three months. CONCLUSIONS A case is described of lymphedema of the transplanted kidney and abdominal wall with ipsilateral pleural effusion following kidney biopsy attributed to her change in anti-rejection therapy to sirolimus. This case report should raise awareness of this unusual complication of sirolimus anti-rejection therapy and its possible effects on the lymphatic system.
[Mh] Termos MeSH primário: Parede Abdominal/diagnóstico por imagem
Imunossupressores/efeitos adversos
Transplante de Rim
Linfedema/induzido quimicamente
Derrame Pleural/induzido quimicamente
Sirolimo/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Biópsia
Feminino
Seres Humanos
Rim/patologia
Linfedema/diagnóstico por imagem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Immunosuppressive Agents); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE


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[PMID]:29232371
[Au] Autor:Brakemeier S; Vogt L; Adams L; Zukunft B; Diederichs G; Hamm B; Budde K; Makowski MR
[Ad] Endereço:Department of Nephrology and Medical Intensive Care, Charité, Berlin, Germany.
[Ti] Título:Treatment effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC).
[So] Source:PLoS One;12(12):e0189132, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML) have a high lifetime risk of acute bleeding. MTOR-inhibitors are a promising novel treatment for TSC-AML, however adequate response to therapy can be difficult to assess. Early changes in MRI signal may serve as a novel early indicator for a satisfactory response to mTOR-inhibitor therapy of AML. MATERIALS AND METHODS: Thirty-eight patients with the definite diagnosis of tuberous sclerosis receiving everolimus therapy and n = 19 patients without specific therapy were included. 1.5 Tesla MRI was performed including sequences with a selective fat suppression. Patients were investigated prior to the initiation of therapy (baseline) and after <3 months (n = 21 patients), 3 to 6 months (n = 32) and 18 to 24 months (n = 28). Signal and size changes of renal AMLs were assessed at all different timepoints. Signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and size of angiomyolipomas were evaluated. RESULTS: Signal changes in 273 AMLs were evaluated. A significant and strong decrease of the CNR of AMLs following the initiation of therapy was measured in the fat-suppressed MR sequence at all time points, compared to the baseline: From 7.41±6.98 to 3.84±6.25 (p ≤ 0.05p = 0.002), 3.36±6.93 (p<0.0001), and 2.50±6.68 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively. Also, a significant, however less pronounced, reduction of angiomyolipoma size in the different groups was measured (from baseline 2022.2±2657.7 mm2 to 1854.4±1670.9 mm2 (p = 0.009), 1875.5±3190.1 mm2 (p<0.001), and 1365.8 ± 1628.8 mm2 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively). No significant changes in CNR (p>0.05) and size (p>0.05) were measured in the control group. CONCLUSION: mTOR inhibitor therapy in TSC patients results in an early and pronounced fatty transformation of AMLs on MRI. Fatty transformation could represent a novel early indicator of response to therapy in this patient collective.
[Mh] Termos MeSH primário: Angiomiolipoma/complicações
Neoplasias Renais/complicações
Sirolimo/uso terapêutico
Serina-Treonina Quinases TOR/antagonistas & inibidores
Esclerose Tuberosa/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Angiomiolipoma/diagnóstico por imagem
Feminino
Seres Humanos
Neoplasias Renais/diagnóstico por imagem
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Razão Sinal-Ruído
Esclerose Tuberosa/complicações
Esclerose Tuberosa/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189132



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