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1.
Pain Physician ; 26(4): E383-E387, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37535785

RESUMO

BACKGROUND: Anesthetic spread of ultrasound-guided paraspinal blocks is still unknown. OBJECTIVES: To compare the drug diffusion qualities of intertransverse process block (ITPB) and erector spinae plane block (ESPB) in clinical practice. STUDY DESIGN: Prospective computed tomography (CT)-3-dimensional (3D) reconstruction image study. SETTING: Operation room in hospital. METHODS: Twenty patients undergoing thoracoscopic pulmonary wedge resection or segmentectomy were enrolled. These procedures require localization of pulmonary nodules using CT-guided needle puncture immediately before surgery. The patients were divided into 2 groups, each consisting of 10 patients. Group I underwent ITPB, while group E underwent ESPB. These interventions were performed 30 minutes before surgery using 20 mL of 0.25% bupivacaine with 2 mL iohexol. Sensory loss of the thoracic dermatomes was assessed using cold stimulation before general anesthesia. Patients' CT localization images were used for 3D reconstruction after surgery, and the diffusion of the drug in each cross-section of the CT images was evaluated. RESULTS: Three-dimensional imaging of the drug showed that in group E, drug diffusion was improved in the cephalocaudal area compared to group I (10 vs 4.5 segments). Drug diffusion in group I was improved anteriorly and laterally ([10/10, 100%] in the paravertebral and intercostal spaces) and reached the front of the vertebral body along the thoracic fascia in certain segments (6/10, 60%). In group E, very few segments of the drug reached the paravertebral (2/10, 20%) and intercostal (3/10, 30%) spaces. All patients in group I had clear signs of loss of cold sensation on the lateral and anterior chest walls, with an average of 4 thoracic dermatomes. In group E, 3 patients had definite lateral and anterior chest wall cold stimulation signs, the thoracic dermatome was discontinuous, and the effect was only present between 1-2 segments. The blocking effect of the paraspinal zone was excellent (100%) in both groups. LIMITATIONS: However, this study has some limitations. First, the sample size was small, and clinical trials with larger samples are required to further verify the effects of ITPB and ESPB. Second, the same local anesthetic drug concentration and volume were used for both techniques in this study, and the effect of volume or concentration on drug diffusion was not further explored. CONCLUSIONS: Compared with ESPB, ITPB yielded increased stability in lateral and anterior chest wall block with improved anterior and intercostal spread, but reduced cephalocaudal spread.


Assuntos
Imageamento Tridimensional , Bloqueio Nervoso , Humanos , Cirurgia Torácica Vídeoassistida , Bloqueio Nervoso/métodos , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos , Punção Espinal , Anestésicos Locais/farmacologia , Dor Pós-Operatória , Músculos Paraespinais
2.
Front Immunol ; 14: 1223567, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37475867

RESUMO

Background: Renal transplantation in HLA-presensitized recipients entails an increased risk of antibody-mediated rejection (AMR) and graft loss. There is currently no accepted standard treatment protocol that can help transplant surgeons safely perform deceased donor (DD) kidney transplantation in presensitized patients without pretransplant desensitization. Methods: Fifty-one panel-reactive antibody (PRA)-positive recipients and 62 PRA-negative retransplant recipients (control) who received DD renal transplantation were included. Patients in the presensitized group (donor-specific antibody [DSA]-positive, n=25; DSA-negative, n=26) without desensitization received a modified perioperative treatment starting on day 0 or -1 with rituximab, thymoglobulin, and low daily doses of intravenous immunoglobulin (IVIG, 10-20 g/d, for 14 days). Plasmapheresis was performed once before surgery in DSA-positive recipients. Results: The median follow-up time was 51 months in the presensitized group and 41 months in the control group. The incidence of early acute rejection (AR) and AMR (including mixed rejection) was 35.3% and 13.7% in the presensitized group, respectively, significantly higher than in the control group (14.5% and 1.6%, respectively). Within the presensitized group, the DSA-positive subgroup had more AMR than the DSA-negative subgroup (24.0% vs. 3.8%), but the incidence of T cell-mediated rejection was comparable (20.0% vs. 23.4%). In the presensitized group, all rejections were successfully reversed, and graft function remained stable during follow-up. The 1-year and 3-year survival rates of the grafts and recipients in this group were 98.0%. Conclusion: With a modified IVIG-based perioperative regimen, excellent intermediate-term graft and recipient survival outcomes can be achieved in presensitized patients who received DD kidney transplantation without prior desensitization.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Anticorpos , Protocolos Clínicos
3.
Biomed Res Int ; 2023: 7629782, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778059

RESUMO

Background: Renal ischemia-reperfusion injury (RIRI) plays an important role in the poor prognosis of patients with renal transplants. However, the potential targets and mechanism of IRI are still unclear. Method: Differential gene expression (DEG) analysis and weighted correlation network analysis (WGCNA) were performed on the GSE27274 dataset. Pathway enrichment analysis on the DEGs was performed. To identify the hub DEGs, we constructed a protein-protein interaction (PPI) network. Finally, the hub genes were verified, and candidate drugs were screened from the DsigDB database. Results: A hundred DEGs and four hub genes (Atf3, Psmb6, Psmb8, and Psmb10) were screened out. Pathway enrichment analysis revealed that 100 DEGs were mainly enriched in apoptosis and the TNF signaling pathway. The four hub genes were verified in animal models and another dataset (GSE148420). Thereafter, a PPI network was used to identify the four hub genes (Atf3, Psmb6, Psmb8, and Psmb10). Finally, eight candidate drugs were identified as potential drugs. Conclusion: Three hub genes (Psmb6, Psmb8, and Psmb10) were associated with RIRI and could be potential novel biomarkers for RIRI.


Assuntos
Redes Reguladoras de Genes , Traumatismo por Reperfusão , Animais , Biomarcadores Tumorais/genética , Biologia Computacional , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/genética , Traumatismo por Reperfusão/genética , Humanos
4.
Immunity ; 56(2): 369-385.e6, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36720219

RESUMO

In allogeneic hematopoietic stem cell transplantation, donor αß T cells attack recipient tissues, causing graft-versus-host disease (GVHD), a major cause of morbidity and mortality. A central question has been how GVHD is sustained despite T cell exhaustion from chronic antigen stimulation. The current model for GVHD holds that disease is maintained through the continued recruitment of alloreactive effectors from blood into affected tissues. Here, we show, using multiple approaches including parabiosis of mice with GVHD, that GVHD is instead primarily maintained locally within diseased tissues. By tracking 1,203 alloreactive T cell clones, we fitted a mathematical model predicting that within each tissue a small number of progenitor T cells maintain a larger effector pool. Consistent with this, we identified a tissue-resident TCF-1+ subpopulation that preferentially engrafted, expanded, and differentiated into effectors upon adoptive transfer. These results suggest that therapies targeting affected tissues and progenitor T cells within them would be effective.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Camundongos , Animais , Linfócitos T , Transplante Homólogo/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos
5.
PLoS One ; 17(11): e0272542, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36417422

RESUMO

Clear cell renal cell carcinoma (ccRCC) is an immunogenic tumor, and investigating the immunorelated genes is essential. To investigate the immunoprognostic genes of ccRCC, we analyzed the data assimilated from a public database (The Cancer Genome Atlas (TCGA) database and the gene expression omnibus (GEO) database) using bioinformatics. Then, an immunoprognosis model was constructed to identify four hub genes with moderate predictive values for the prognosis of ccRCC patients. These four genes were associated with the prognosis of ccRCC patients based on Oncomine and Gena Expression Profiling Interactive Analysis (GEPIA) databases. The correlation analysis between the immune infiltrate, immune checkpoints, and immunotherapy and this immunoprognosis model showed that immune infiltration could predict the immunotherapy effects. We also conducted a quantitative real-time polymerase chain reaction analysis and found that the expressions of three hub genes were associated with tumor progression (P<0.1). In conclusion, four genes that may serve as potential biomarkers in ccRCC were identified with respect to prognosis.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/metabolismo , Prognóstico , Biologia Computacional/métodos , Neoplasias Renais/genética , Neoplasias Renais/terapia , Neoplasias Renais/metabolismo , Imunoterapia
6.
Front Med (Lausanne) ; 9: 838738, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308516

RESUMO

ABO blood group antibodies have not been generated or are at low titer during early infancy. Therefore, in theory, ABO-incompatible kidney transplantation (ABOi KT) may be successfully achieved in small infants without any pre-transplant treatment. We report here the first ABO-incompatible deceased donor kidney transplantation (ABOi DDKT) in an infant. The recipient infant was ABO blood group O, and the donor group A. The recipient was diagnosed with a Wilms tumor gene 1 (WT1) mutation and had received peritoneal dialysis for 4 months prior to transplant. At 7 months and 27 days of age, the infant underwent bilateral native nephrectomy and single-kidney transplantation from a 3-year-old brain-dead donor. No pre- or post-transplantation antibody removal treatment was performed, since the recipient's anti-iso-hemagglutinin-A Ig-M/G antibody titers were both low (1:2) before transplantation and have remained at low levels or undetectable to date. At 11 months post-transplant, the recipient is at home, thriving, with normal development and graft function. This outcome suggests that ABOi DDKT without antibody removal preparatory treatment is feasible in small infants, providing a new option for kidney transplantation in this age range.

7.
Eur J Anaesthesiol ; 38(4): 366-373, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492871

RESUMO

BACKGROUND: Ultrasound-guided posterior lumbar plexus block is widely used for hip fracture surgery but it requires a change of position, which may be painful. OBJECTIVES: Our primary objective was to describe a new technique, the anterior iliopsoas muscle space block, which can be performed in the supine position, and to test the hypothesis that its analgesia for hip surgery was similar to that of the traditional posterior lumbar plexus block. DESIGN: Randomised, double-blind study. SETTING: Shanghai 6th People's Hospital, China, from February to August 2019. PATIENTS: Forty-eight patients scheduled for unilateral hip fracture surgery were included in the study. The exclusion criteria were infection at the puncture site, history of hip surgery, pre-existing neurological deficits of the lower extremity, contraindications for regional anaesthesia, allergy to local anaesthetics, coagulopathy, abuse of medicine or alcohol, or daily consumption of analgesics. INTERVENTIONS: Patients were randomised to receive a lateral sacral plexus block with either an anterior iliopsoas muscle space block or a posterior lumbar plexus block, using 0.33% ropivacaine (30 ml each). MAIN OUTCOME MEASURES: The main outcome was verbal numerical scale (VNS) pain intensity 1 h after surgery in the postanesthesia care unit, and the secondary outcome was the dose of intra-operative fentanyl. The differences in VNS scores and fentanyl use between the groups were analysed. RESULTS: Based on previous work, we considered a difference (confidence interval [CI]) of 1.6 on the VNS to be significant. The median [IQR] pain scores in postanesthesia care unit were similar in the anterior 0 [0 to 3] and posterior groups 1.5 [0 to 3]. The median scores for intra-operative fentanyl use were similar in the anterior 20 [10 to 42.5] µg and posterior groups 15 [0 to 50] µg (P = 0.34). The difference in the median pain score at-rest was NS: anterior group 0.5 [0 to 5], posterior group 0 [0 to 2], median difference -0.5 (95% CI -2 to 0). The median post to preblock difference in VNS was higher in the anterior -0.5 [-2 to 0] than in the posterior group 0 [-1.25 to 0], median difference 0.5 (95% CI 0 to 1). The median block onset time was longer in the anterior 11 [6 to 14.25] min than in the posterior group 6 [4.75 to 8] min (P = 0.002), median difference -5 (95% CI -7 to -1). CONCLUSION: The anterior iliopsoas muscle space block had the same effect as the posterior lumbar plexus block on peri-operative analgesia for hip surgery, but with a longer onset time. Therefore, anterior iliopsoas muscle space block can be recommended as a routine technique for hip and lower limb procedures. TRIAL REGISTRATION: http://www.chictr.org.cn identifier: ChiCTR1900021214.


Assuntos
Bloqueio Nervoso , Idoso , Anestésicos Locais , China , Humanos , Plexo Lombossacral/diagnóstico por imagem , Músculos , Bloqueio Nervoso/efeitos adversos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Ultrassonografia de Intervenção
8.
J Mol Cell Cardiol ; 154: 80-91, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33378686

RESUMO

Obesity-driven cardiac lipid accumulation can progress to lipotoxic cardiomyopathy. Soluble epoxide hydrolase (sEH) is the major enzyme that metabolizes epoxyeicosatrienoic acids (EETs), which have biological activity of regulating lipid metabolism. The current study explores the unknown role of sEH deficiency in lipotoxic cardiomyopathy and its underlying mechanism. Wild-type and Ephx2 knock out (sEH KO) C57BL/6 J mice were fed with high-fat diet (HFD) for 24 weeks to induce lipotoxic cardiomyopathy animal models. Palmitic acid (PA) was utilized to induce lipotoxicity to cardiomyocytes for in vitro study. We found sEH KO, independent of plasma lipid and blood pressures, significantly attenuated HFD-induced myocardial lipid accumulation and cardiac dysfunction in vivo. HFD-induced lipotoxic cardiomyopathy and dysfunction of adenosine 5'-monophosphate-activated protein kinase-mammalian target of rapamycin complex (AMPK-mTORC) signaling mediated lipid autophagy in heart were restored by sEH KO. In primary neonatal mouse cardiomyocytes, both sEH KO and sEH substrate EETs plus sEH inhibitor AUDA treatments attenuated PA-induced lipid accumulation. These effects were blocked by inhibition of AMPK or autophagy. The outcomes were supported by the results that sEH KO and EETs plus AUDA rescued HFD- and PA-induced impairment of autophagy upstream signaling of AMPK-mTORC, respectively. These findings revealed that sEH deficiency played an important role in attenuating myocardial lipid accumulation and provided new insights into treating lipotoxic cardiomyopathy. Regulation of autophagy via AMPK-mTORC signaling pathway is one of the underlying mechanisms.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Epóxido Hidrolases/deficiência , Miocárdio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Biomarcadores , Cardiomiopatias/fisiopatologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Metabolismo dos Lipídeos , Camundongos , Camundongos Knockout
9.
Signal Transduct Target Ther ; 5(1): 194, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32934199

RESUMO

Modulation of alloimmune responses is critical to improving transplant outcome and promoting long-term graft survival. To determine mechanisms by which a nonhematopoietic erythropoietin (EPO) derivative, carbamylated EPO (CEPO), regulates innate and adaptive immune cells and affects renal allograft survival, we utilized a rat model of fully MHC-mismatched kidney transplantation. CEPO administration markedly extended the survival time of kidney allografts compared with the transplant alone control group. This therapeutic effect was inhibited when the recipients were given LY294002, a selective inhibitor of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway or anti-EPO receptor (EPOR) antibody, in addition to CEPO. In vitro, CEPO inhibited the differentiation and function of dendritic cells and modulated their production of pro-inflammatory and anti-inflammatory cytokines, along with activating the PI3K/AKT signaling pathway and increasing EPOR mRNA and protein expression by these innate immune cells. Moreover, after CD4+ T cells were exposed to CEPO the Th1/Th2 ratio decreased and the regulatory T cell (Treg)/Th17 ratio increased. These effects were abolished by LY294002 or anti-EPOR antibody, suggesting that CEPO regulates immune responses and promotes kidney allograft survival by activating the PI3K/AKT signaling pathway in an EPOR-dependent manner. The immunomodulatory and specific signaling pathway effects of CEPO identified in this study suggest a potential therapeutic approach to promoting kidney transplant survival.


Assuntos
Eritropoetina/análogos & derivados , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Rim , Rim/imunologia , Transdução de Sinais/efeitos dos fármacos , Aloenxertos , Animais , Eritropoetina/farmacologia , Sobrevivência de Enxerto/imunologia , Masculino , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Ratos , Ratos Endogâmicos Lew , Transdução de Sinais/imunologia
10.
Science ; 368(6495): 1122-1127, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32381589

RESUMO

Immunological memory specific to previously encountered antigens is a cardinal feature of adaptive lymphoid cells. However, it is unknown whether innate myeloid cells retain memory of prior antigenic stimulation and respond to it more vigorously on subsequent encounters. In this work, we show that murine monocytes and macrophages acquire memory specific to major histocompatibility complex I (MHC-I) antigens, and we identify A-type paired immunoglobulin-like receptors (PIR-As) as the MHC-I receptors necessary for the memory response. We demonstrate that deleting PIR-A in the recipient or blocking PIR-A binding to donor MHC-I molecules blocks memory and attenuates kidney and heart allograft rejection. Thus, innate myeloid cells acquire alloantigen-specific memory that can be targeted to improve transplant outcomes.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Imunidade Inata , Memória Imunológica , Macrófagos/imunologia , Monócitos/imunologia , Receptores Imunológicos/fisiologia , Animais , Deleção de Genes , Rejeição de Enxerto/genética , Transplante de Coração , Transplante de Rim , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Receptores Imunológicos/genética
11.
Am J Emerg Med ; 38(6): 1137-1140, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31685304

RESUMO

BACKGROUND: To determine the level of inspiratory pressure minimizing the risk of gastric insufflation while providing adequate pulmonary ventilation. METHODS: In this prospective, randomized, double-blind study, patients were allocated to one of the two groups (P10, P15) defined by the inspiratory pressure applied during controlled-pressure ventilation: 10 and 15 cm H2O. Anesthesia was induced using propofol and sufentanil; no neuromuscular-blocking agent was administered. Once loss of eyelash reflex occurred, facemask ventilation was started for a 2-min period. The cross-sectional antral area was measured using ultrasonography before and after facemask ventilation. Respiratory parameters were recorded. RESULTS: Forty patients were analyzed. Mean tidal volume was about 7 ml/kg in group P10, and was >11 ml/kg in group P15 in the same period. As indicated by ultrasonography test, the antral area in P15 group was markedly incresed compared with P10 group. CONCLUSION: Inspiratory pressure of 10 cm H2O allowed for reduced occurrence of gastric insufflation with proper lung ventilation during induction of anesthesia with sufentanil and propofol in nonparalyzed and nonobese patients.


Assuntos
Anestesia Geral/métodos , Insuflação/efeitos adversos , Complicações Intraoperatórias/prevenção & controle , Máscaras Laríngeas/normas , Respiração Artificial/instrumentação , Estômago/lesões , Pressão do Ar , Estudos Transversais , Método Duplo-Cego , Feminino , Humanos , Complicações Intraoperatórias/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estômago/diagnóstico por imagem , Volume de Ventilação Pulmonar , Ultrassonografia
12.
J Transl Med ; 16(1): 52, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29514693

RESUMO

BACKGROUND: Kidneys from deceased donors are being used to meet the growing need for grafts. However, delayed graft function (DGF) and acute rejection incidences are high, leading to adverse effects on graft outcomes. Optimal induction intervention should include both renal structure injury repair and immune response suppression. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative, and immune-modulatory properties are considered a candidate to prevent DGF and acute rejection in renal transplantation. Thus, this prospective multicenter paired study aimed to assess the clinical value of allogeneic MSCs as induction therapy to prevent both DGF and acute rejection in deceased donor renal transplantation. METHODS: Forty-two renal allograft recipients were recruited and divided into trial and control groups. The trial group (21 cases) received 2 × 106/kg human umbilical-cord-derived MSCs (UC-MSCs) via the peripheral vein before renal transplantation, and 5 × 106 cells via the renal artery during the surgical procedure. All recipients received standard induction therapy. Incidences of DGF and biopsy-proven acute rejection were recorded postoperatively and severe postoperative complications were assessed. Graft and recipient survivals were also evaluated. RESULTS: Treatment with UC-MSCs achieved comparable graft and recipient survivals with non-MSC treatment (P = 0.97 and 0.15, respectively). No increase in postoperative complications, including DGF and acute rejection, were observed (incidence of DGF: 9.5% in the MSC group versus 33.3% in the non-MSC group, P = 0.13; Incidence of acute rejection: 14.3% versus 4.8%, P = 0.61). Equal postoperative estimated glomerular filtration rates were found between the two groups (P = 0.88). All patients tolerated the MSCs infusion without adverse clinical effects. Additionally, a multiprobe fluorescence in situ hybridization assay revealed that UC-MSCs administered via the renal artery were absent from the recipient's biopsy sample. CONCLUSIONS: Umbilical-cord-derived MSCs can be used as clinically feasible and safe induction therapy. Adequate timing and frequency of UC-MSCs administration may have a significant effect on graft and recipient outcomes. Trial registration NCT02490020 . Registered on June 29 2015.


Assuntos
Transplante de Rim , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Adulto , Estudos de Viabilidade , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Estimativa de Kaplan-Meier , Masculino , Projetos Piloto , Complicações Pós-Operatórias/etiologia , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento , Cordão Umbilical/citologia
13.
Int J Mol Med ; 41(1): 25-32, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115389

RESUMO

Ischemia/reperfusion injury (IRI) commonly occurs in renal transplantation. Erythropoietin (EPO) exerts a protective effect in IRI. To investigate the underlying molecular mechanism, rat models of renal IRI were established and treated with EPO and/or lentivirus­mediated EPO-siRNA, the signal transducer and activator of transcription 6 (STAT6) inhibitor AS1517499, the JNK inhibitor SP600125, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, and the nuclear factor (NF)-κB inhibitor lactacystin. Histological examination revealed that EPO protected the kidney from IRI, through decreasing the extent of tissue congestion and inflammatory cell infiltration; however, EPO siRNA did not exert the same protective effect. In addition, the EPO level was inversely associated with renal IRI. EPO downregulated the expression of interferon-γ, interleukin (IL)-4, creatinine and caspase-3, and upregulated the expression of IL-10, thymic stromal lymphopoietin, STAT6, p-JNK and p-p38, while the opposite effects were observed with the administration of EPO-siRNA and the specific respective inhibitors. Further results revealed that MAPK (p-JNK and p-p38) acted upstream of NF-κB, and that NF-κB signaling regulated the expression of caspase-1 and -3, which may be responsible for the cytotoxicity associated with IRI. Taken together, the results of the present study demonstrated that EPO exerted a protective effect in renal IRI via the STAT6/MAPK/NF-κB pathway. This protective effect of EPO may improve reperfusion tolerance in ischemic kidneys and benefit transplant recipients.


Assuntos
Eritropoetina/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Fator de Transcrição STAT6/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Acetilcisteína/administração & dosagem , Acetilcisteína/análogos & derivados , Animais , Antracenos/administração & dosagem , Apoptose/efeitos dos fármacos , Apoptose/genética , Eritropoetina/genética , Regulação da Expressão Gênica/genética , Humanos , Imidazóis/administração & dosagem , Interferon gama/genética , Rim/metabolismo , Rim/patologia , Transplante de Rim/efeitos adversos , Lentivirus/genética , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/genética , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Piridinas/administração & dosagem , Pirimidinas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Ratos , Traumatismo por Reperfusão/patologia , Fator de Transcrição STAT6/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(12): 1655-1659, 2016 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-27998860

RESUMO

OBJECTIVE: To explore the anesthetic effect and safety of ultrasound-guided thoracic paravertebral blockade in video-assisted thoracoscopic sympathectomy for treatment of palmar hyperhidrosis. METHODS: A total of 120 patients undergoing video-assisted thoracoscopic sympathectomy for moderate or severe hyperhidrosis were randomized to receive ultrasound-guided thoracic paravertebral blockade (group A, n=60) or general anesthesia with tracheal intubation (group B, n=60). In both groups routine monitoring and radial artery catheterization were used. The patients in group A were given oxygen inhalation via a nasal tube after thoracic paravertebral blockade, and those in group B had intratracheal intubation. Blood gas analyses were conducted 5 min before and 5 min after the operation and the clinical outcomes and complications were recorded in each group. RESULTS: All the patients completed the operations safely and none of the patients with thoracic paravertebral blockade required conversion to general anesthesia. Significant differences were recorded between groups A and B in anesthetic preparation time (6.26∓2.09 vs 46.32∓15.76 min), awakening time (6.26∓2.09 vs 46.32∓15.76 min), and mean hospitalization expense (6355.54∓426.00 vs 8932.25∓725.98 RMB Yuan). Compared with those in group B, the patients in group A showed a significantly lower rate of postoperative throat discomfort (0% vs 100%), a shorter monitoring time (2 h vs 12 h), and faster recovery time for food intake (2 h vs 6 h). The parameters of artery blood gas analysis both before and after the operation were similar between the two groups, but the postoperative variations differed significantly between the two groups in pH value and PaCO2 but not in PaO2. CONCLUSION: Ultrasound-guided thoracic paravertebral blockade is safe and effective in video-assisted thoracoscopic sympathectomy for palmar hyperhidrosis and is associated with less complications and better postoperative recovery.


Assuntos
Hiperidrose/cirurgia , Bloqueio Nervoso/métodos , Simpatectomia , Cirurgia Torácica Vídeoassistida , Anestésicos , Humanos , Período Pós-Operatório , Resultado do Tratamento , Ultrassonografia
15.
Mol Immunol ; 79: 22-31, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27689750

RESUMO

Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance. In this study, BN rat recipients were pre-injected with donor renal alloantigen-treated recipient iDCs before kidney transplantation. The renal allograft exhibited a lighter renal rejection response, prolonged graft survival time, and an increasing content of CD4+CD25+Foxp3+ regulatory T cells (Tregs). Additionally, up-regulated secretion of Th2 cytokines were found in recipient sera post-transplantation. Transfection of si-IDO1 RNA into renal-antigen-treated recipient iDCs reversed these changes, which suggested that IDO channel signaling may be involved in iDC-induced allograft immunotolerance. These results suggested that iDC-induced and IDO-mediated allograft immunotolerance might be a potentially feasible tactic to prolong allograft survival, in addition to immunosuppressive drugs.


Assuntos
Células Dendríticas/imunologia , Tolerância Imunológica/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Transplante de Rim , Imunologia de Transplantes/imunologia , Aloenxertos/imunologia , Animais , Western Blotting , Células Dendríticas/enzimologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Sobrevivência de Enxerto , Células-Tronco Hematopoéticas/enzimologia , Células-Tronco Hematopoéticas/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Teste de Cultura Mista de Linfócitos , Masculino , Ratos , Linfócitos T Reguladores/imunologia
17.
J Trauma Acute Care Surg ; 73(4): 869-73, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22836002

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the effect of percutaneous cardiopulmonary support (PCPS) for fatal fat embolism. METHODS: Twelve piglets were randomly assigned into either a conventional treatment group (CT group, n = 6) or a PCPS group (n = 6) after receiving 0.3 mL/kg of fat intravenously. The piglets in the CT group received conventional treatments including mechanical ventilation with 100% oxygen, steroid, fluids, anticoagulant, and positive inotropic agents. In addition to conventional treatments, the piglets in the PCPS group received PCPS after fat injection. Mean arterial pressure, central venous pressure, pressure of end tidal carbon dioxide, oxygen saturation, partial pressure of oxygen in arterial blood, arterial carbon dioxide pressure or tension, plasmic lactic acid, and free fatty acid were monitored. The survival rate and the consumption of positive inotropic agents were also recorded. RESULTS: The survival rate of piglets 10 hours after fat injection was much higher in the PCPS group than that in the CT group (100% vs. 0%, p < 0.01). The dosages of positive inotropic agents in the PCPS group were much lower than that in the CT group (p < 0.01). Oxygen saturation, partial pressure of oxygen in arterial blood, and arterial carbon dioxide pressure or tension were significantly improved in the PCPS group in the first 3 hours after fat injection when compared with those in the CT group (p < 0.05 or 0.01), but there were no statistical differences between the two groups in mean arterial pressure, central venous pressure, free fatty acid, and lactic acid at the period. CONCLUSION: PCPS can increase the survival rate of piglets with fatal fat embolism by providing effective cardiopulmonary support. This study suggests that PCPS might be an effective treatment for a patient with severe fat embolism if conventional treatments have not worked.


Assuntos
Reanimação Cardiopulmonar/métodos , Cateterismo Periférico , Embolia Gordurosa/terapia , Animais , Modelos Animais de Doenças , Embolia Gordurosa/etiologia , Índice de Gravidade de Doença , Suínos , Resultado do Tratamento , Ferimentos e Lesões/complicações
18.
Chin Med J (Engl) ; 124(17): 2723-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22040431

RESUMO

BACKGROUND: Thymokidney has been reported as an approach for a vascularized thymus for transplantation to induce donor specific tolerance. A completely thymectomized model which ensures that the obtained thymus is not injured has not been developed yet and it would be useful for evaluating autologous thymokidney function in rats. METHODS: Adult Sprague-Dawley male rats weighing 150 - 300 g (n = 30) underwent non-invasive intubation with the assistance of an improved self-made wedge-shaped cannula made from a 2-ml plastic syringe and transillumination from the anterior tracheal area by an operation spotlight. The rats then received a thoracotomy while their breathing was supported by a small animal ventilator, and both lobes of the thymus were entirely extirpated under a 10× microscope. The postoperative survival rate of the rats was recorded, and changes in the T-cell reservoir from 9 of 30 rats within 21 days after surgery were monitored using flow cytometry. The complete thymectomy rate was confirmed by autopsy and histological examination on 21 days post-operation. RESULTS: The postoperative survival rate of rats was 100%. The exsected thymus was free of injury and the rate of complete thymectomy was 100%. CONCLUSIONS: This model has a stable survival rate and complete thymectomy is able to be achieved. The obtained thymus tissue is free of injury and can be used for transplantation.


Assuntos
Intubação Intratraqueal/métodos , Timectomia/métodos , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Toracotomia/métodos , Timo/cirurgia
19.
Clin Transplant ; 24(5): 599-609, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19925472

RESUMO

BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) in renal transplant recipients is an important cause of renal transplant dysfunction. Our aim was to determine the kinetics of BKV load within one yr after kidney transplantation under the impact of intensive monitoring and reduction in maintenance immunosuppression, the incidence of BKVAN, and the outcome of BKVAN treatment. METHODS: Urine and peripheral blood (PB) were taken from 90 renal transplant recipients for BKV cytological testing and real-time PCR for BKV DNA at one, three, six, nine, and 12 months after transplantation and treatment. Graft biopsies and urinary sediments of recipients with BKVAN were taken to monitor viral particles by conventional transmission electron microscopy (TEM). RESULTS: By one post-transplant year, urinary decoy cells (median, 8/10 HPF), BKV viruria (median, 2.60 × 10(5) copies/mL), viremia (median, 9.65 × 10(3) copies/mL), and BKVAN occurred in 42.2%, 45.6%, 22.2%, and 5.6% of patients, respectively. The incidence of BK infection was lower in patients who received cyclosporine A (CsA) (28.9%) compared to tacrolimus (FK506) (57.7%) (p = 0.007). An increased hazard of BK infection was associated with the use of FK506 (HR 2.6, p = 0.009) relative to CsA. After reduction in immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction, or graft loss. BKVAN was diagnosed in five patients (5.6%). The treatment of immunosuppression reduction was effective (i.e., decreased the viral load and number of decoy cells, and improved graft function) in our five patients with BKVAN. Quantitative count of decoy cells (e.g., >10 per 10 HPF) as a marker of viremia and BKVAN had increased positive predictive values of 85.7% and 57.1%, respectively. CONCLUSIONS: Choice of FK506 as immunosuppressive agent is an independent risk factor affecting BKV infection. Monitoring and pre-emptive of immunosuppression reduction were associated with resolution of viremia and showed effective in BKVAN recipients at the early stage without acute rejection or graft loss. Quantitative count of urine cytology is a very convenient, useful, and sensitive method for evaluating BKV infection in renal transplant recipients.


Assuntos
Vírus BK/fisiologia , Nefropatias/etiologia , Transplante de Rim , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Replicação Viral , Adulto , China , DNA Viral , Feminino , Rejeição de Enxerto , Humanos , Tolerância Imunológica , Imunossupressores/uso terapêutico , Incidência , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/genética , Estudos Prospectivos , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/genética , Viremia/complicações , Viremia/genética , Viremia/virologia
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