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1.
Clin Rheumatol ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907850

RESUMO

BACKGROUND: To systematically describe clinical characteristics and investigate factors associated with COVID-19-related infection, hospital admission, and IgG4-related disease relapse in IgG4-RD patients. METHODS: Physician-reported IgG4-RD patients were included in this retrospective study. Using multivariable logistic regression analysis to determine factors for primary outcome (COVID-19-related IgG4-RD relapse) and secondary outcome (COVID-19-related infection and hospital admission). Covariates included age, sex, body mass index, smoking status, comorbidities, IgG4-RD clinical features, and treatment strategies. RESULTS: Among 649 patients, 530 had a diagnosis of COVID-19, 25 had COVID-19-related hospital admission, and 69 had COVID-19-related IgG4-RD relapse. Independent factors associated with COVID-19 infection were age (OR, 0.98; 95% CI, 0.96-1.00), body mass index (1.10, 1.03-1.18), and tofacitinib (0.34, 0.14-0.79). Further analysis indicated that age (1.10, 1.03-1.16), coronary heart disease (24.38, 3.33-178.33), COVID-19-related dyspnea (7.11, 1.85-27.34), pulmonary infection (73.63, 16.22-4615.34), and methotrexate (17.15, 1.93-157.79) were associated with a higher risk of COVID-19-related hospital admission. Importantly, age (0.93, 0.89-0.98), male sex (0.16, 0.03-0.80), ever/current smoking (19.23, 3.78-97.80), COVID-19-related headache (2.98, 1.09-8.17) and psychiatric symptoms (3.12, 1.07-9.10), disease activity before COVID-19 (1.89, 1.02-3.51), number of involved organs (1.38, 1.08-1.76), glucocorticoid dosage (1.08, 1.03-1.13), and methotrexate (5.56, 1.40-22.08) were strong factors for COVID-19-related IgG4-RD relapse. CONCLUSIONS: Our data add to evidence that smoking and disease-specific factors (disease activity, number of involved organs, and specific medications) were risk factors of COVID-19-related IgG4-RD relapse. The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate and increasing glucocorticoid dosages in the COVID-19 era. Key Points • COVID-19-related infection or hospital admission were associated with known general factors (age, body mass index, specific comorbidities and methotrexate) among IgG4-RD patients. • Smoking and disease-specific factors (disease activity, number of involved organs and specific medications) were associated with higher odds of COVID-19-related IgG4-RD relapse. • The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate or increasing glucocorticoid dosages.

2.
Clin Rheumatol ; 43(6): 2027-2034, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38625643

RESUMO

OBJECTIVES: Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. METHODS: We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. RESULTS: In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24 h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. CONCLUSIONS: Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.


Assuntos
Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Gota , Inflamação , Macrófagos , Perforina , Ácido Úrico , Animais , Linfócitos T CD8-Positivos/imunologia , Camundongos , Macrófagos/metabolismo , Macrófagos/imunologia , Perforina/metabolismo , Gota/imunologia , Gota/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Citotóxicas Formadoras de Poros
3.
Immunology ; 168(3): 554-568, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36273262

RESUMO

The development of many systemic autoimmune diseases, including systemic lupus erythematosus, is associated with overactivation of the type I interferon (IFN) pathway, lymphopenia and increased follicular helper T (Tfh)-cell differentiation. However, the cellular and molecular mechanisms underlying these immunological perturbations remain incompletely understood. Here, we show that the mechanistic target of rapamycin complex 2 (mTORC2) promotes Tfh differentiation and disrupts Treg homeostasis. Inactivation of mTORC2 in total T cells, but not in Tregs, greatly ameliorated the immunopathology in a systemic autoimmunity mouse model. This was associated with reduced Tfh differentiation, B-cell activation, and reduced T-cell glucose metabolism. Finally, we show that type I IFN can synergize with TCR ligation to activate mTORC2 in T cells, which partially contributes to T-cell lymphopenia. These data indicate that mTORC2 may act as downstream of type I IFN, TCR and costimulatory receptor ICOS, to promote glucose metabolism, Tfh differentiation, and T-cell lymphopenia, but not to suppress Treg function in systemic autoimmunity. Our results suggest that mTORC2 might be a rational target for systemic autoimmunity treatment.


Assuntos
Autoimunidade , Lúpus Eritematoso Sistêmico , Camundongos , Animais , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Linfócitos T Auxiliares-Indutores , Diferenciação Celular , Receptores de Antígenos de Linfócitos T/metabolismo , Glucose/metabolismo
4.
Cell Rep ; 31(6): 107621, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32402289

RESUMO

Follicular helper T cells (Tfhs) are essential for germinal center (GC) B cell maturation and antibody development. However, the intrinsic mechanisms that regulate Tfh differentiation are largely unknown. Here, we demonstrate that the frequencies of Tfhs and GC B cells, as well as interleukin-21 (IL-21) and anti-ovalbumin (OVA) antibodies, are markedly decreased in forkhead box O3 (Foxo3) knockout mice immunized with OVA. Using mixed bone marrow chimeras and lymphocyte-repopulated Rag1-/- mice proves that wild-type (WT), but not Foxo3-deficient T cells provoke GC B cell maturation and antibody production. Deficiency of Foxo3 inhibits inducible T cell co-stimulator (ICOS)-induced Tfh differentiation. Chromatin immunoprecipitation assay results suggest that Foxo3 is able to bind to the IL-21 promoter and regulate IL-21 secretion. In conclusion, our study unveils a critical role of Foxo3 in the regulation of Tfh differentiation and IL-21 production. Modulating Foxo3 activity may be beneficial for enhancing or preventing antibody-mediated immune responses.


Assuntos
Proteína Forkhead Box O3/imunologia , Células T Auxiliares Foliculares/imunologia , Animais , Diferenciação Celular/imunologia , Proteína Forkhead Box O3/deficiência , Imunidade Humoral , Proteína Coestimuladora de Linfócitos T Induzíveis/antagonistas & inibidores , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Subunidade alfa de Receptor de Interleucina-21/genética , Subunidade alfa de Receptor de Interleucina-21/imunologia , Masculino , Camundongos , Camundongos Knockout , Regiões Promotoras Genéticas , Células T Auxiliares Foliculares/citologia
5.
Clin Rheumatol ; 38(5): 1425-1431, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30645753

RESUMO

OBJECTIVES: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM). In this study, we examined the level and origin of serum-soluble TRAIL (sTRAIL) in patients with PM and DM and analyzed its association with disease activity and clinical features. METHOD: 11 PM patients, 33 DM patients, and 20 healthy controls were enrolled in this study. Clinical features were recorded when admitted, and disease activity was evaluated by myositis disease activity assessment visual analogue scale (MYOACT). TRAIL expression in muscle tissues was detected by immunohistochemistry. Serum sTRAIL levels were measured by enzyme-linked immunosorbent assay. The expression of membrane TRAIL (mTRAIL) and its receptors, including DR4 and DR5, on circulating T cells was analyzed by flow cytometry. RESULTS: TRAIL was expressed in infiltrated inflammatory cells in muscle tissues from patients. The serum sTRAIL level was markedly increased in patients and was positively correlated with the disease activity. Serum sTRAIL was decreased after therapy in patients and was specifically higher in patients with dysphagia, but lower in patients with autoantibody Jo-1 positive. The frequency of mTRAIL and its receptors on circulating T cells from patients were significantly elevated than that from healthy controls. CONCLUSIONS: The serum sTRAIL could be a biomarker for evaluating the disease activity of PM and DM, and targeting the generation of TRAIL in T cells might be a potential approach in the treatment of PM and DM.


Assuntos
Dermatomiosite/sangue , Polimiosite/sangue , Linfócitos T/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , China , Dermatomiosite/patologia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimiosite/patologia , Adulto Jovem
6.
Mol Med Rep ; 16(5): 6306-6312, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28849043

RESUMO

Acute pancreatitis (AP) is a common non­bacterial disease compromising pancreatic tissues. Adipocyte­derived leptin is closely associated with the severity and clinical outcome of pancreatitis. The potential protective effects of exogenous leptin administration on a rat model of severe AP (SAP) remain to be elucidated, and were examined in the present study. Male Wistar rats were divided into a sham operation group (SO), SAP model group (SAP) and leptin group (LEP). Each group was divided into three sub­groups by observation time (24, 48 and 72 h). The SAP models were prepared by retrograde injection of 6% sodium taurocholate into the pancreatic­bile duct. Following model establishment, exogenous leptin was intraperitoneally injected into mice at 50 mg/kg in the LEP group. Subsequently, serum amylase, lipase and glucose levels at particular time­points were analyzed using a fully­automatic biochemical analyzer, and serum levels of tumor necrosis factor (TNF)­α and interleukin (IL)­10 were detected using an enzyme­linked immunosorbent assay. The pathological changes in pancreatic tissues were observed using hematoxylin and eosin staining, and the pancreatic expression of the long form of the leptin receptor (OB­Rb) was detected and evaluated using Nest­polymerase chain reaction analysis. The mortality rates of the model rats were compared between the groups. Following the administration of exogenous leptin, the serum level of amylase in the LEP group was significantly decreased at 48 h, compared with that in the SAP group, with serum lipase levels decreased at 48 and 72 h, and blood glucose levels decreased at 72 h. Regarding the serum inflammatory factors, the level of TNF­α in the LEP group was significantly lower, compared with that in the SAP group at 24 h; whereas no significant difference was observed in the serum level of IL­10 between the two groups. Regarding the pathological changes in the pancreas, the tissues in the LEP group showed significantly alleviated pancreatic inflammation. In addition, the pancreatic expression of OB­Rb in the LEP group was significantly higher, compared with that in the SAP group at 24 and 48 h. No significant difference in 3­day mortality rates were observed between the SAP group and the LEP group. Taken together, exogenous leptin administration regulated inflammatory factors and the expression of OB­Rb at the early stage of AP, which exerted protective effects by through the immunological and endocrinal pathways.


Assuntos
Leptina/farmacologia , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Substâncias Protetoras/farmacologia , Ácido Taurocólico/farmacologia , Doença Aguda , Amilases/sangue , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-10/metabolismo , Lipase/sangue , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pancreatite/metabolismo , Ratos , Ratos Wistar , Receptores para Leptina/metabolismo , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
7.
World J Emerg Med ; 7(2): 130-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27313808

RESUMO

BACKGROUND: Diarrhea is frequently seen in developed and developing countries, and severe diarrhea is characterized by the high risk of death. Thus, it is very important to assess the severity of diarrhea early. We conducted a multi-center study to identify risk factors for the severity of diarrhea in adult patients and formulate an adult diarrhea state score (ADSS) for out-patient clinicians. METHODS: A total of 219 adult patients with acute diarrhea were divided into two groups: 132 patients with mild diarrhea and 87 with severe diarrhea. Logistic regression was used to determine risk factors for the severity of diarrhea. The risk factors were assessed and an ADSS was formulated. Receiver operating characteristic (ROC) analysis was made to evaluate the diagnostic accuracy of ADSS, and the Kappa test was used to confirm the diagnostic reliability. RESULTS: Five risk factors for evaluating the severity of diarrhea in adults included age (P<0.05), axillary temperature (P<0.01), mean arterial pressure (P<0.01), white blood cell count (WBC; P<0.01), and WBC in stool (P<0.01). The area under the ROC curve for ADSS was 0.958 when the cut off value was 4 (a sensitivity of 0.909; a specificity of 0.874), and the Kappa value was 0.781 (P<0.05). CONCLUSION: The risk factors associated with the pathogenic condition of diarrhea were identified, quantified and formulated into an ADSS, which has high diagnostic accuracy and reliability for the early identification of patients with severe acute diarrhea.

8.
Pancreas ; 44(2): 266-72, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25426615

RESUMO

OBJECTIVE: Angiotensin-converting enzyme 2 (ACE2), its product angiotensin-(1-7), and its receptor Mas have been shown to moderate the adverse effects of the ACE-angiotensin II-AT1 axis in many diseases. The aim of this study was to determine whether the ACE2-Ang-(1-7)-Mas axis could have similar effects in a cell culture model of pancreatic damage. METHODS: AR42J cells were stimulated with 10 nmol/L cerulein to simulate acute pancreatitis. ACE2, Ang-(1-7), Mas receptor, and PI3K/AKT pathway were measured by quantitative real-time polymerase chain reaction and Western blot analysis. RESULTS: ACE2 and Mas receptor protein levels in AR42J cells were significantly increased (P < 0.05) between 30 minutes and 6 hours postdisease induction compared with the control group. Mas receptor gene expression was significantly increased (P < 0.05) at 2 hours postdisease induction, and Ang-(1-7) was increased at 6 hours. Treatment with Ang-(1-7) in AR42J cells increased IL-10, decreased IL-6 and IL-8, and reduced the damage to pancreatic cells. Levels of IL-6 and IL-8 in AR42J cell culture were increased significantly after treatment with A779. Moreover, Ang-(1-7) increased the concentration of PI3K/AKT pathway and eNOSin AR42J cells. CONCLUSIONS: ACE2-angiotensin-(1-7)-Mas axis significantly inhibits pancreatitis in response to decreased inflammatory factors by the activation of endothelial nitric oxide synthase and NO signaling pathways.


Assuntos
Angiotensina I/farmacologia , Anti-Inflamatórios/farmacologia , Pâncreas Exócrino/efeitos dos fármacos , Pancreatite/prevenção & controle , Fragmentos de Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Linhagem Celular , Ceruletídeo/toxicidade , Citoproteção , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Pâncreas Exócrino/enzimologia , Pâncreas Exócrino/patologia , Pancreatite/enzimologia , Pancreatite/patologia , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/genética , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
9.
Intern Med ; 53(16): 1869-72, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25130127

RESUMO

Adult-onset Still's disease (AOSD) is a multisystemic inflammatory disorder, but pulmonary involvement is rare. We herein describe the case of a woman diagnosed with AOSD; treatment resolved her symptoms, but nine days later she was admitted with pyrexia and a productive cough. A chest X-ray revealed diffuse pulmonary nodules and patchy shadows. A high-resolution chest computed tomography scan confirmed diffuse infiltration in the pulmonary parenchyma, signs of alveolar nodules, distribution along the lobule center, several areas of tree-in-bud patterns, and bilateral pleural effusion. The patient was treated with high doses of corticosteroids, which rapidly reduced the size of her diffuse pulmonary nodules and dramatically improved her pleural effusion.


Assuntos
Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/etiologia , Derrame Pleural/etiologia , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/diagnóstico , Corticosteroides/uso terapêutico , Feminino , Febre/diagnóstico por imagem , Febre/tratamento farmacológico , Febre/etiologia , Humanos , Pulmão/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/tratamento farmacológico , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/tratamento farmacológico , Radiografia , Doença de Still de Início Tardio/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
10.
J Gastroenterol Hepatol ; 29(6): 1328-37, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24628092

RESUMO

BACKGROUND AND AIM: Ulinastatin is a drug used effectively to alleviate symptoms and improve the pathophysiology of various types of pancreatitis. However, the molecular mechanism responsible for its action remains unknown. Therefore, we further explore the therapeutic effects of ulinastatin and investigate possible molecular pathways modulated by this drug in the development of severe acute pancreatitis (SAP). METHODS: SAP mouse model was created by administering intraperitoneal injections of cerulein and lipopolysaccharide. Pancreatic injury was assessed by performing biochemical and histological assays and by measuring the inflammatory response of the pancreas. Specifically, we examined changes in the expression of components of the rennin-angiotensin system (RAS), including angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-angiotensin type 1 receptor (AT-1R), and ACE2-Ang-(1-7)-Mas receptor. RESULTS: When SAP mouse models were treated with ulinastatin at a dosage of 50,000 U/kg body weight, we found, through biochemical and histopathological analyses, that the pancreatic injury was significantly ameliorated. Administration of ulinastatin to SAP mice led to increased expression of ACE2, Ang-(1-7), and Mas receptor, decreased expression of serum Ang II and pancreatic AT-1R, and no alterations in the expression of pancreatic ACE and Ang II when compared to cerulein-treated control group that did not receive ulinastatin. CONCLUSIONS: This study shows that ulinastatin has differential effects on the two axes of the RAS during SAP. Our results further suggest that upregulation of components of the ACE2-Ang-(1-7)-Mas pathway might be an important mechanism contributing to the therapeutic role of ulinastatin in alleviating pancreatitis-associated symptoms.


Assuntos
Glicoproteínas/administração & dosagem , Terapia de Alvo Molecular , Pancreatite/tratamento farmacológico , Pancreatite/genética , Sistema Renina-Angiotensina/fisiologia , Doença Aguda , Angiotensina I/genética , Angiotensina I/metabolismo , Angiotensina II/genética , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Ceruletídeo , Modelos Animais de Doenças , Expressão Gênica , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Pancreatite/induzido quimicamente , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Estudos Prospectivos , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Renina-Angiotensina/genética , Índice de Gravidade de Doença
11.
Exp Physiol ; 99(4): 651-63, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24414175

RESUMO

Angiotensin-converting enzyme (ACE) and its effector peptide angiotensin II (Ang II) have been implicated in the pathogenesis of pancreatitis. Angiotensin-converting enzyme 2 (ACE2) degrades Ang II to angiotensin-(1-7) [Ang-(1-7)] and has recently been described to have an antagonistic effect on ACE signalling. However, the specific underlying role of ACE2 in the pathogenesis of severe acute pancreatitis (SAP) is unclear. In the present study, the local imbalance of ACE and ACE2, as well as Ang II and Ang-(1-7) expression, was compared in wild-type (WT) and ACE2 knock-out (KO) or ACE2 transgenic (TG) mice subjected to cerulein-induced SAP. Serum amylase, tumour necrosis factor-α, interleukin (IL)-1ß, IL-6 and IL-10 levels and histological morphometry were used to determine the severity of pancreatitis. In WT mice, pancreatic ACE and Ang II and serum Ang II expression increased (P < 0.05), while pancreatic ACE2 and Ang-(1-7) and serum Ang-(1-7) levels were also significantly elevated (P < 0.05) from 2 to 72 h after the onset of SAP. However, the ratio of pancreatic ACE2 to ACE expression was significantly reduced (from 1.46 ± 0.09 to 0.27 ± 0.05, P < 0.001) and paralleled the severity of pancreatitis. The Ace2 KO mice exhibited increased levels of tumour necrosis factor-α, IL-1ß, IL-6, multifocal coagulative necrosis and inflammatory infiltrate, and lower levels of serum IL-10 and pancreatic Ang-(1-7) (4.70 ± 2.13 versus 10.87 ± 2.51, P < 0.001) compared with cerulein-treated WT mice at the same time point. Conversely, Ace2 TG mice with normal ACE expression were more resistant to SAP challenge as evidenced by a decreased inflammatory response, attenuated pathological changes and increased survival rates. These data suggest that the ACE2-ACE imbalance plays an important role in the pathogenesis of SAP and that pancreatic ACE2 is an important factor in determining the severity of SAP.


Assuntos
Ceruletídeo , Pâncreas/enzimologia , Pancreatite/enzimologia , Peptidil Dipeptidase A/metabolismo , Doença Aguda , Amilases/sangue , Angiotensina I/sangue , Angiotensina II/sangue , Enzima de Conversão de Angiotensina 2 , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Genótipo , Mediadores da Inflamação/sangue , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Necrose , Pâncreas/patologia , Pancreatite/genética , Pancreatite/patologia , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/deficiência , Peptidil Dipeptidase A/genética , Fenótipo , Índice de Gravidade de Doença , Fatores de Tempo
12.
Am J Chin Med ; 41(2): 263-80, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23548118

RESUMO

Rheumatoid arthritis (RA) is the most common chronic inflammatory disease with unknown causes and unknown cures in Western medicine. This double-blinded study aimed to investigate the efficacy and safety of a widely used traditional Chinese medicine (Paeoniflorin (PAE) plus cervus and cucumis polypeptide injection (CCPI) using disease-modifying antirheumatic drugs (DMARD) as a control (methotrexate (MTX) plus leflunomide (LEF)). Patients were randomly assigned to one of the three groups: PAE + CCPI, MTX + LEF, and MTX + LEF + CCPI. The primary end point was the American College of Rheumatology 20% improvement response criteria (ACR20). The secondary end point was that of adverse effect frequencies and the speed of onset action. Our results showed that more patients in the CCPI-containing groups responded to the ACR20 during early treatment. After six months, ACR20 showed no significant difference among the three treatments. The maximum improvement in the two DMARD groups was significantly higher than that in the PAE + CCPI group (p < 0.01). CCPI made the onset action of the DMARD therapy 4.6 times faster. PAE + CCPI had significantly lower adverse event incidences than the two DMARD groups. These results indicate that PAE + CCPI appear to be a more acceptable alternative to DMARDs when patients cannot use DMARDs. CCPI appears to be a beneficial add-on to DMARDs that makes the onset of action faster, especially when patients need to relieve RA symptoms as soon as possible. Although not as effective as DMARDs, PAE appears to be a safer option to substitute DMARDs for long-term RA treatment when DMARD toxicity is an issue.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
13.
Pancreatology ; 12(5): 451-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23127535

RESUMO

BACKGROUND/OBJECTIVES: Angiotensin-converting enzyme 2 (ACE2), its product angiotensin-(1-7) and its receptor Mas may counteract the adverse effects of the ACE-angiotensin receptor II-AT(1) axis in many diseases. We examined the expression of these novel components of the rennin-angiotensin system in an experimental mouse model of severe acute pancreatitis (SAP). METHODS: SAP was induced by six intraperitoneal injections of caerulein, and mice were sacrificed at 2, 12, 24, 48 and 72 h post disease-induction (normal control group mice were sacrificed at 2 h post disease-induction). Tissue and blood were collected for biochemical detection, gene and protein expression by qRT-PCR and western blot analysis, enzyme-linked immunosorbent assay and immunohistology detection. RESULTS: Pancreatic ACE2 gene and protein expression, plasma and pancreatic angiotensin-(1-7) levels and Mas receptor gene and protein expression were significantly increased (p < 0.05) following SAP induction compared with the normal control group. CONCLUSIONS: Severe acute pancreatitis is associated with upregulation of the ACE2-angiotensin-(1-7)-Mas axis and promotes increased circulating angiotensin-(1-7). These results support the presence of an ACE2-angiotensin-(1-7)-Mas axis in pancreatitis.


Assuntos
Angiotensina I/sangue , Pancreatite/fisiopatologia , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Sistema Renina-Angiotensina/fisiologia , Doença Aguda , Enzima de Conversão de Angiotensina 2 , Animais , Ceruletídeo , Modelos Animais de Doenças , Masculino , Camundongos , Pâncreas/metabolismo , Pancreatite/induzido quimicamente , Proto-Oncogene Mas , Regulação para Cima
14.
J Eval Clin Pract ; 18(4): 721-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21651679

RESUMO

RATIONALE, AIMS AND OBJECTIVES: Acute fever is the most common early clinical symptom of many critical illnesses with a high mortality rate. It is necessary to identify patients with severe acute fever early and accurately. The aim of this study is to identify risk factors for critically ill outpatients with acute fever and formulate activation criteria of adult fever state score (AFSS) to alert outpatient clinic doctors. METHODS: Retrospectively, 357 adult patients with acute fever were divided into two groups: 180 patients with a severe state and 177 patients with a mild state. Logistic regression was used to determine risk factors for the severe state. Risk factors were weighted and an AFSS was formulated. A receiver operating characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of AFSS, and the kappa test was used to confirm diagnostic reliability. A χ(2) -test for trend was applied to determine the relevance between AFSS and admission rate and in-hospital mortality. A Kruskal-Wallis test was used to examine the relationship between AFSS and length of stay. RESULTS: Risk factors for state included: old age, long fever course, past medical history, abnormal temperature, abnormal respiratory rate, abnormal heart rate, abnormal mean arterial pressure and abnormal peripheral white blood cell count. The area under the ROC curve of AFSS was 0.964 and ≥8 points predicted severe state; the Kappa value was 0.801. With an increase in score, there was an increase in admission rate, mortality rate and length of stay. The forecast performance of AFSS was superior to the modified early warning score. CONCLUSIONS: The AFSS has high diagnostic accuracy and reliability for the early identification of patients with severe acute fever.


Assuntos
Instituições de Assistência Ambulatorial , Comunicação , Febre/etiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Índice de Gravidade de Doença , Adulto Jovem
16.
Trop Doct ; 41(2): 76-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21296846

RESUMO

Human ocular angiostrongyliasis caused by Angiostrongylus cantonensis infection in the eye is a very rare condition. Until now, there has been no comprehensive analysis of this disease. We searched and analysed the references found on the Internet that refer to human ocular angiostrongyliasis and reviewed the aetiology, clinical manifestations, diagnosis, epidemiology and treatment of the condition. Twenty-six references were found reporting 35 patients from 10 countries that were diagnosed with human ocular angiostrongyliasis. People are usually infected by eating raw or undercooked intermediate hosts of the parasite such as snails or contaminated vegetables. The most common symptom was visual loss. Although several treatments have been used, ocular angiostrongyliasis can still result in permanent visual impairment and may even cause blindness. As the eye is the site of infection and direct visualization is possible, ocular examination is crucial for diagnosis. The therapeutic success depended on early and complete surgical removal.


Assuntos
Angiostrongylus cantonensis/isolamento & purificação , Infecções Oculares Parasitárias/diagnóstico , Infecções por Strongylida/diagnóstico , Animais , Infecções Oculares Parasitárias/complicações , Infecções Oculares Parasitárias/cirurgia , Humanos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Infecções por Strongylida/parasitologia , Infecções por Strongylida/cirurgia , Fatores de Tempo , Resultado do Tratamento , Transtornos da Visão/parasitologia
17.
Am J Trop Med Hyg ; 83(6): 1352-5, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21118948

RESUMO

Angiostrongyliasis is a globally distributed parasitic disease. Early and accurate identification of patients with severe infection is required. In this retrospective study, 81 patients with angiostrongyliasis were divided into two groups: 24 patients with severe disease and 57 with mild disease. Logistic regression analysis was used to determine the factors associated with severe disease. Receiver operating characteristic (ROC) analysis, κ tests, and χ(2) tests were performed. The factors analyzed included: headache (P = 0.013), abnormal cerebrospinal fluid pressure (P = 0.013), and abnormal peripheral blood eosinophil count (P = 0.007). The area under the ROC curve for the activation criteria for angiostrongyliasis (ACA) was 0.914, with a score of ≥ 7 points predicting a severe state; the κ value was 0.744. The incidence of severe angiostrongyliasis increased with increasing score. ACA is a useful tool with high accuracy and reliability for predicting the severity of angiostrongyliasis.


Assuntos
Infecções por Strongylida , Corticosteroides/uso terapêutico , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Infecções por Strongylida/classificação , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/patologia
18.
J Eval Clin Pract ; 16(6): 1248-53, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20722883

RESUMO

RATIONALE, AIMS AND OBJECTIVES: Acute fever is the most common clinical symptom for infectious diseases. It is necessary to identify risk factors for infectious patients with acute fever and formulate activation criteria of early warning infectiosity score system (EWIS) to alert outpatient clinic doctors. METHODS: Logistic regression analysis was used to determine risk factors for infectious diseases from the clinical data of 758 patients with acute fever. Risk factors were weighted and an EWIS was formulated. A receiver operator characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of EWIS, and the Kappa test used to confirm diagnostic reliability. A χ(2) -test for trend was applied to determine the relevance between EWIS and incidence of infectious diseases. RESULTS: Risk factors for infections included conjunctival hyperaemia, rash, diarrhoea, increased alanine aminotransferase, splenomegaly and abnormal percentage of peripheral neutrophils (NE%). Risk factors were weighted and tabulated. The areas under the ROC curves of the EWIS was 0.929 and ≥ 4 points predicted infectious diseases, and the Kappa values were 0.750. As the score increased, the incidence of infectious diseases increased. The areas under the ROC curves of the EWIS predicting on single viral and bacterial infectious diseases were 0.961 and 0.896, and the Kappa values were 0.807 and 0.701, respectively. CONCLUSIONS: Risk factors for infections have been identified, quantified and formulated into a table of EWIS that have high diagnostic accuracy and reliability for the early identification of contagious diseases.


Assuntos
Instituições de Assistência Ambulatorial , Doenças Transmissíveis/etiologia , Febre/etiologia , Médicos , Sensibilidade e Especificidade , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Transmissíveis/classificação , Comunicação , Feminino , Febre/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Análise de Regressão , Fatores de Risco , Adulto Jovem
19.
J Parasitol ; 96(2): 377-81, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19874073

RESUMO

An outbreak of 81 cases of angiostrongyliasis cantonensis (AC) occurred in Beijing, China, during June through September 2006. Epidemiological characteristics, clinical signs and symptoms, laboratory tests, imaging, and treatment data from the 81 AC patients were collected and analyzed. All cases had a history of eating raw freshwater snails, and acquired Angiostrongylus cantonensis as a result. The incubation period ranged from 1 to 36 days. The main symptoms were fever, severe headache, neck stiffness, and skin paresthesia. A significant increase in eosinophilia occurred in the peripheral blood of 62 cases and in cerebrospinal fluid of 64 cases; 36 patients presented a linearly enhanced abnormal signal of the leptomeninges site during a cranial MRI examination, indicative of meningitis; 18 cases had a significant nodule shadow and spot flaky ground-glass shadow on chest computerized tomography. All patients were relieved of their illness with a 7-day treatment of albendazole.


Assuntos
Angiostrongylus cantonensis/isolamento & purificação , Surtos de Doenças , Infecções por Strongylida/epidemiologia , Adolescente , Adulto , Animais , Sistema Nervoso Central/patologia , China/epidemiologia , Feminino , Febre , Parasitologia de Alimentos , Água Doce , Cefaleia , Humanos , Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cervicalgia , Parestesia , Prognóstico , Radiografia , Frutos do Mar/parasitologia , Caramujos/parasitologia , Infecções por Strongylida/diagnóstico , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/etiologia , Adulto Jovem
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