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1.
Emerg Med J ; 41(6): 354-360, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38521512

RESUMO

BACKGROUND: Fascia iliaca block (FIB) is an effective technique for analgesia. While FIB using ultrasound is preferred, there is no current standardised training technique or assessment scale. We aimed to create a valid and reliable tool to assess ultrasound-guided FIB. METHOD: This prospective observational study was conducted in the ABS-Lab simulation centre, University of Poitiers, France between 26-29 October and 14-17 December 2021. Psychometric testing included validity analysis and reliability between two independent observers. Content validity was established using the Delphi method. Three rounds of feedback were required to reach consensus. To validate the scale, 26 residents and 24 emergency physicians performed a simulated FIB on SIMLIFE, a simulator using a pulsated, revascularised and reventilated cadaver. Validity was tested using Cronbach's α coefficient for internal consistency. Comparative and Spearman's correlation analysis was performed to determine whether the scale discriminated by learner experience with FIB and professional status. Reliability was analysed using the intraclass correlation (ICC) coefficient and a correlation score using linear regression (R2). RESULTS: The final 30-item scale had 8 parts scoring 30 points: patient positioning, preparation of aseptic and tools, anatomical and ultrasound identification, local anaesthesia, needle insertion, injection, final ultrasound control and signs of local anaesthetic systemic toxicity. Psychometric characteristics were as follows: Cronbach's α was 0.83, ICC was 0.96 and R2 was 0.91. The performance score was significantly higher for learners with FIB experience compared with those without experience: 26.5 (22.0; 29.0) vs 22.5 (16.0; 26.0), respectively (p=0.02). There was a significant difference between emergency residents' and emergency physicians' scores: 20.5 (17.0; 25.0) vs 27.0 (26.0; 29.0), respectively (p=0.0001). The performance was correlated with clinical experience (Rho=0.858, p<0.0001). CONCLUSION: This assessment scale was found to be valid, reliable and able to identify different levels of experience with ultrasound-guided FIB.


Assuntos
Competência Clínica , Fáscia , Bloqueio Nervoso , Ultrassonografia de Intervenção , Humanos , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos , Ultrassonografia de Intervenção/normas , Reprodutibilidade dos Testes , Bloqueio Nervoso/métodos , Bloqueio Nervoso/normas , Fáscia/diagnóstico por imagem , Adulto , Competência Clínica/normas , Masculino , Feminino , França , Treinamento por Simulação/métodos , Psicometria/métodos , Psicometria/instrumentação , Técnica Delphi
2.
Surg Innov ; : 15533506241292698, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39411873

RESUMO

BACKGROUND: In surgical simulation, evaluation tools are necessary to allow the overall and specific level of each gesture to be assessed for learners, to allow active feedback and follow-up. The aim of this study was to create and validate a scale for the assessment of competences for neck dissection (ND) and total laryngectomy (TL) in head and neck surgical oncology simulation specific for revascularized cadavers' models. METHODS: Two independent scales were created for ND and TL based on a two-round Delphi method. The scales were used during ND and TL simulation sessions on SimLife® (Symedis, Poitiers, France) model. Surgical steps were scored by 2 independent observers. To assess its ease of use, a questionnaire was answered by senior surgeons (SS) at the end of the sessions. RESULTS: Fifteen items were included in the final version for ND scale and 20 for TL scale. The results of 14 lateral ND and 8 TL were included. The mean score was higher for SS (69 ± 6.4; 87.5 ± 8.5) than for residents (36.5 ± 11; 57.5 ± 13.2) for ND (P = 0.0006) and TL (P = 0.028) respectively. Six SS strongly agreed that this tool had a positive impact on resident training with stepwise feedback and accurately represented their competences. CONCLUSION: We developed a pedagogic tool built to assess surgical competence for head and neck surgical oncology on revascularized cadaver models. This tool has a good construct validity thanks to the expert reviewing with Delphi method and appears to have fine acceptability by the SS.

3.
Infect Immun ; 82(7): 2881-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24778119

RESUMO

Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Quimiocinas/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Helicobacter pylori/imunologia , Estômago/citologia , Antígenos de Bactérias/imunologia , Peptídeos Catiônicos Antimicrobianos/genética , Proteínas de Bactérias/imunologia , Células Cultivadas , Quimiocinas/genética , Ilhas Genômicas , Helicobacter pylori/metabolismo , Humanos
4.
J Robot Surg ; 18(1): 322, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141249

RESUMO

Cost, logistics, and availability of robotic simulation opportunities suppose a real challenge for robotic surgery training. We aimed to test a new methodology for introduction to robotic surgery pre-congress courses. Two different "introduction to robotic surgery" pre-congress courses were developed. A new methodology using a sleeve/bypass, a ventral TAPP and an inguinal TAPP silicone models was implemented. After the session, the trainees answered a questionnaire to evaluate the course and the methodology using 1-5 Likert scales. A total of 21 participants participated in the courses and (72.2%) had no experience in robotic surgery. All trainees rated the course as good or excellent. There was a strong agreement between participants regarding the adequacy of the silicone models for this type of simulation/course. Trainees agree that the course gave them more confidence to perform a real robotic procedure, increased their interest in robotic surgery and made them feel ready to start their robotic surgery pathway. Congresses are a frequent way of contact between surgeons and robotic systems, mostly in the form of technical demonstrations or pre-congress courses. Our methodology showed that it is possible to allow for this contact in a low-cost way. This kind of courses is well received by congress delegates and have a positive educational impact. Despite of being "Discovery" courses, they have a positive impact on the congress, on the acquisition of robotic surgery skills and increase the interest in robotic surgery.


Assuntos
Competência Clínica , Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Robóticos/educação , Procedimentos Cirúrgicos Robóticos/métodos , Humanos , Inquéritos e Questionários , Treinamento por Simulação/métodos
5.
Otolaryngol Head Neck Surg ; 170(3): 972-976, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38111133

RESUMO

The SimLife® model consists in a human cadaver dynamized by pulsatile vascularization. The objective was to evaluate the face, contents, and constructs validity of the SimLife® model in head and neck surgical oncology simulation. Head and neck surgical oncology simulation sessions on SimLife® models were organized with lateral neck dissection and total laryngectomy. Face and contents validity were addressed by questionnaires. Constructs validity was assessed by objective structured assessment of technical skills (OSATS) score. High realism was demonstrated for consistency of tissues (7.1 ± 1.4), color of arteries and veins (7.3 ± 1.9, 8.5 ± 1.1, respectively), and vein consistency (8.5 ± 1.2). The mean OSATS score was 19.7 ± 5.4 for residents and 32.7 ± 1.9 for senior surgeon (P = .0022). SimLife® is a hyperrealistic model for head and neck surgical oncology simulation and it might become a core component of the surgical resident curriculum.


Assuntos
Internato e Residência , Treinamento por Simulação , Oncologia Cirúrgica , Humanos , Pescoço , Cabeça , Currículo , Competência Clínica
6.
Microb Drug Resist ; 26(6): 677-680, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31750765

RESUMO

Helicobacter pylori and non-H. pylori Helicobacter (NHPH) are associated with gastritis, ulcer, and gastric neoplasia. Because of the impossibility to culture them, diagnosis remains based on microscopic examination and molecular analysis of biopsies. Owing to the lack of data concerning antibiotic resistance of NHPH, infected patients are usually treated using antibiotics, including clarithromycin. Herein, we describe, for the first time a human infection by Helicobacter suis harboring a mutation associated to clarithromycin resistance in H. pylori. Eradication was successful with a metronidazole-based treatment. This observation highlights the benefit to use genotypic detection of resistance to improve therapeutic management of NHPH infections.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Resistência Microbiana a Medicamentos/genética , Helicobacter heilmannii/efeitos dos fármacos , Helicobacter heilmannii/genética , Helicobacter pylori/genética , Adulto , Feminino , Infecções por Helicobacter/tratamento farmacológico , Humanos , Metronidazol/uso terapêutico , Mutação
7.
J Clin Med ; 9(9)2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32878081

RESUMO

This study aims to determine the gastric distribution, density, and diversity of Helicobacter pylori infection. Subtotal resection of the stomachs of three H. pylori-infected and asymptomatic obese patients were collected after a sleeve gastrectomy. Distribution and density of H. pylori were determined using culture and RT-PCR on multiple gastric sites (88, 176, and 101 biopsies per patient). Diversity of H. pylori strains was studied using antibiotic susceptibility testing, random amplified polymorphism DNA (RAPD) typing and cagA gene detection on single-colony isolates (44, 96, and 49 isolates per patient). H. pylori was detected in nearly all analyzed sites (354/365 biopsies, 97%). Antral density was higher in one patient only. The three stomachs were almost exclusively infected by an antibiotic-susceptible strain. One clarithromycin-resistant isolate in one biopsy was detected in two stomachs (1/44 and 1/49 isolates), while in the third one, eight (8/96 isolates) metronidazole-resistant isolates were detected. DNA typing showed infection with cagA-negative strains for one patient, cagA-positive strains for a second patient and the third patient was infected with two different strains of distinct cagA genotypes. Infection with H. pylori is shown to spread to the whole surface of the stomach, but a possibility of minor sub-population of antibiotic-resistant clones, undetectable in routine practice.

8.
Surg Radiol Anat ; 31(8): 585-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19266140

RESUMO

BACKGROUND: Development of the digestive tract during the human fetal period has been the subject of many studies, but there are no works that study the ontogeny of both the right colon and the peritoneum. METHODS: Based on the dissections of adult male cadavers and human fetuses, the aim of this anatomical study was to demonstrate the rules of the morpho-functional group, consisting of the right colon and its peritoneum surface, in human ontogeny. RESULTS: The morphology of the right colon results from a rotational motion, inducting the migration of the cecum in the right iliac fossa and formation of the hepatic flexure. This intestinal migration is based on the axis of rotation of the spreading area of the colon at the ventral side of the lower pole of the right kidney, which becomes visible after the 17th week. CONCLUSION: Our different observations plead in favor of the peritoneal fusion theory. A few variations of this fusion can explain all the disorders in the position of the cecum-appendix that are encountered in current surgery, as well as the possibility of internal hernias.


Assuntos
Colo/embriologia , Feto/embriologia , Peritônio/embriologia , Adulto , Feminino , Humanos , Masculino
9.
Ophthalmic Res ; 40(3-4): 181-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18421236

RESUMO

PURPOSE: We aimed to describe the clinical and angiographic changes in an experimental model of autoimmune uveoretinitis and vasculitis in primates. METHODS: Six cynomolgus monkeys received a single subcutaneous immunization with 100 microg of human S antigen with complete Freund's adjuvant. RESULTS: All the animals had a bilateral long-term disease occurring usually in 1 eye approximately 4 weeks after immunization, the second eye being involved 1-5 weeks later. A cyclic course of the disease could be demonstrated by repeated fundus fluorescein angiograms. The initial and principal manifestation consisted in retinal vascular sheathing affecting veins and venules. The more severe forms showed areas of posterior uveoretinitis, dense vitritis and anterior uveitis. CONCLUSION: A single systemic injection of pure human retinal S antigen could induce a chronic and recurrent ocular disease similar to human retinal vasculitis.


Assuntos
Modelos Animais de Doenças , Retina/patologia , Vasculite Retiniana/diagnóstico , Veia Retiniana/patologia , Retinite/diagnóstico , Uveíte/diagnóstico , Corpo Vítreo/patologia , Adjuvantes Imunológicos , Animais , Arrestina , Progressão da Doença , Angiofluoresceinografia , Seguimentos , Adjuvante de Freund , Fundo de Olho , Imunização/efeitos adversos , Fotocoagulação a Laser , Macaca fascicularis , Microscopia Acústica , Recidiva , Retina/diagnóstico por imagem , Vasculite Retiniana/induzido quimicamente , Vasculite Retiniana/cirurgia , Retinite/induzido quimicamente , Retinite/cirurgia , Índice de Gravidade de Doença , Uveíte/induzido quimicamente , Uveíte/cirurgia , Corpo Vítreo/diagnóstico por imagem
10.
Surg Laparosc Endosc Percutan Tech ; 17(6): 495-9, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18097307

RESUMO

PURPOSE: This study compares open Hartmann's procedure reversal (OHPR) and laparoscopic Hartmann's procedure reversal (LHPR) in patients first treated for peritonitis (Henchey III or IV). METHODS: Fourteen patients who underwent LHPR during a 2-year period were compared with 20 patients who had previously undergone an open procedure at the same institution. RESULTS: Conversion rate was 14.28%. Operating time was shorter for the laparoscopic group [143 (90 to 240) vs. 180 (90 to 350) min, P<0.05]. Hospital length of stay was shorter for the laparoscopic group [9.5 (4 to 18) vs. 11 (6 to 39)]. Use of patient-controlled analgesia was not significantly shorter in the laparoscopic group [3 (0 to 4) vs. 3.5 (0 to 8)]. Morbidities observed in the LHPR group include a parietal abscess and an anastomotic stenosis without surgical treatment. The OHPR group had 6 complications: 1 anastomotic leak and 5 incisional hernias. CONCLUSIONS: LHPR with a conversion rate of 14.28% seems to be a method with shorter operating time and less morbidity compared with OHPR.


Assuntos
Anastomose Cirúrgica/métodos , Colostomia , Laparoscopia/estatística & dados numéricos , Peritonite/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Período Intraoperatório/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Reoperação , Fatores de Tempo , Resultado do Tratamento
11.
Biochem Pharmacol ; 66(11): 2241-50, 2003 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-14609748

RESUMO

Ischemia-reperfusion injury (IRI) is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria plays a central role in this process. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in HEH after 24 hr and particularly 48- and 72-hr cold storage than in CEL and UW. TMZ improved the preservation quality when added to the different solutions tested, particularly after 48- and 72-hr cold storage. Interstitial fibrosis and tubular atrophy were reduced in HEH with TMZ. CD4(+) T-cell infiltration was also modulated by the preservation conditions. Peripheral-type benzodiazepine receptor (PBR) positive cells infiltration was also modulated by preservation conditions. TMZ was efficient to reduce IRI when added in the various preservation solutions. These results suggest that protection of the mitochondrial function should be a major target to limit IRI. In addition, this study outlines the role of CD4(+) T cells and PBR expression in inflammatory responses after IRI.


Assuntos
Temperatura Baixa , Sistemas de Liberação de Medicamentos/métodos , Isquemia/tratamento farmacológico , Nefrite/tratamento farmacológico , Néfrons/irrigação sanguínea , Néfrons/efeitos dos fármacos , Trimetazidina/uso terapêutico , Animais , Isquemia/metabolismo , Isquemia/prevenção & controle , Testes de Função Renal , Medula Renal/irrigação sanguínea , Medula Renal/efeitos dos fármacos , Medula Renal/fisiopatologia , Nefrite/metabolismo , Nefrite/fisiopatologia , Néfrons/metabolismo , Néfrons/fisiopatologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Suínos , Transplante Autólogo
12.
Rev Prat ; 53(15): 1639-44, 2003 Oct 15.
Artigo em Francês | MEDLINE | ID: mdl-14689907

RESUMO

Abdomen can be compared in broad outline with an irregular cylinder, limited at the top by the diaphragm and below by the pond. The walls of this cylinder are musculo-aponevrotic and present "zones of weakness" seats of the hernias of the abdominal wall. We propose a topographic anatomical approach of abdominal hernias.


Assuntos
Parede Abdominal/patologia , Hérnia Ventral/fisiopatologia , Parede Abdominal/anatomia & histologia , Hérnia Inguinal/fisiopatologia , Hérnia Ventral/congênito , Humanos , Fatores de Risco
14.
Transplantation ; 89(8): 937-44, 2010 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-20134394

RESUMO

BACKGROUND: Interleukin (IL)-15 is a chemotactic factor to T cells. It induces proliferation and promotes survival of activated T cells. IL-15 receptor blockade in mouse cardiac and islet allotransplant models has led to long-term engraftment and a regulatory T-cell environment. This study investigated the efficacy of IL-15 receptor blockade using Mut-IL-15/Fc in an outbred non-human primate model of renal allotransplantation. METHODS: Male cynomolgus macaque donor-recipient pairs were selected based on ABO typing, major histocompatibility complex class I typing, and carboxy-fluorescein diacetate succinimidyl ester-based mixed lymphocyte responses. Once animals were assigned to one of six treatment groups, they underwent renal transplantation and bilateral native nephrectomy. Serum creatinine level was monitored twice weekly and as indicated, and protocol biopsies were performed. Rejection was defined as a increase in serum creatinine to 1.5 mg/dL or higher and was confirmed histologically. Complete blood counts and flow cytometric analyses were performed periodically posttransplant; pharmacokinetic parameters of Mut-IL-15/Fc were assessed. RESULTS: Compared with control animals, Mut-IL-15/Fc-treated animals did not demonstrate increased graft survival despite adequate serum levels of Mut-IL-15/Fc. Flow cytometric analysis of white blood cell subgroups demonstrated a decrease in CD8 T-cell and natural killer cell numbers, although this did not reach statistical significance. Interestingly, two animals receiving Mut-IL-15/Fc developed infectious complications, but no infection was seen in control animals. Renal pathology varied widely. CONCLUSIONS: Peritransplant IL-15 receptor blockade does not prolong allograft survival in non-human primate renal transplantation; however, it reduces the number of CD8 T cells and natural killer cells in the peripheral blood.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/farmacologia , Imunossupressores/farmacologia , Transplante de Rim , Receptores de Interleucina-15/antagonistas & inibidores , Animais , Soro Antilinfocitário/farmacologia , Biomarcadores/sangue , Biópsia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Creatinina/sangue , Quimioterapia Combinada , Citometria de Fluxo , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/farmacocinética , Transplante de Rim/efeitos adversos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Macaca fascicularis , Masculino , Camundongos , Modelos Animais , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacologia , Receptores de Interleucina-15/imunologia , Fatores de Tempo , Transplante Homólogo
15.
J Pharmacol Exp Ther ; 302(3): 861-70, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12183641

RESUMO

Ischemia-reperfusion injury (IRI) after transplantation is a major cause of delayed graft function, which has a negative impact on early and late graft function and improve acute rejection. We have previously shown that polyethylene glycol (PEG) and particularly PEG 20M has a protective effect against cold ischemia and reperfusion injury in an isolated perfused pig and rat kidney model. We extended those observations to investigate the role of PEG using different doses (30g or 50g/l) added (ICPEG30 or ICPEG50) or not (IC) to a simplified preservation solution to reduce IRI after prolonged cold storage (48-h) of pig kidneys when compared with Euro-Collins and University of Wisconsin solutions. The study of renal function and medulla injury was performed with biochemical methods and proton NMR spectroscopy. Histological and inflammatory cell studies were performed after reperfusion (30-40 min) and on days 7 and 14 and weeks 4, 8, and 12. Peripheral-type benzodiazepine receptor (PBR), a mitochondrial protein involved in cholesterol homeostasis, was also studied. The results demonstrated that ICPEG30 improved renal function and reduced medulla injury. ICPEG30 also improved tubular function and strongly protect mitochondrial integrity. Post-IRI inflammation was strongly reduced in this group, particularly lymphocytes TCD4(+), PBR expression was influenced by IRI in the early period and during the development of chronic dysfunction. This study clearly shows that PEG has a beneficial effect in renal preservation and suggests a role of PBR as a marker IRI and repair processes.


Assuntos
Medula Renal/patologia , Polietilenoglicóis/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Animais , Temperatura Baixa , Selectina E/biossíntese , Selectina E/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Genes MHC da Classe II/genética , Imuno-Histoquímica , Testes de Função Renal , Medula Renal/metabolismo , Transplante de Rim/fisiologia , Espectroscopia de Ressonância Magnética , Nefrectomia , Oxirredução , Ratos , Suínos , Molécula 1 de Adesão de Célula Vascular/biossíntese , Molécula 1 de Adesão de Célula Vascular/genética
16.
Pharmacology ; 71(1): 25-37, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15051920

RESUMO

In organ transplantation, ischemia-reperfusion injury (IRI) has been implicated in delayed graft function (DGF) as well as in short- and long-term complications. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in CEL, UW and particularly HEH in combination with TMZ, particularly after 48 and 72 h. Mitochondria integrity was improved in TMZ-preserved groups. This study indicates that TMZ is efficiently protective against IRI even after prolonged preservation and in different preservation solutions.


Assuntos
Criopreservação , Mitocôndrias/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Trimetazidina/farmacologia , Adenosina/farmacologia , Alopurinol/farmacologia , Animais , Biomarcadores , Dissacarídeos/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Eletrólitos/farmacologia , Glutamatos/farmacologia , Glutationa/farmacologia , Histidina/farmacologia , Insulina/farmacologia , Testes de Função Renal/métodos , Transplante de Rim/métodos , Transplante de Rim/mortalidade , Manitol/farmacologia , Mitocôndrias/fisiologia , Mitocôndrias/ultraestrutura , Preservação de Órgãos/métodos , Soluções para Preservação de Órgãos/farmacologia , Rafinose/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Suínos , Fatores de Tempo , Transplante Autólogo/métodos , Transplante Autólogo/mortalidade
17.
Am J Transplant ; 4(4): 495-504, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15023141

RESUMO

Ischemia-reperfusion injury (IRI) represents an allo-independent risk factor which favors chronic allograft nephropathy (CAN). Here we analyzed the influence of preservation solutions on the function of autotransplanted pig kidneys over 1-16 weeks after surgery. Kidneys were cold-flushed and cold-stored for 24 or 48 h either in University of Wisconsin (UW), modified-UW Hôpital Edouard Herriot, polyethylene glycol 20 kDa (PEG)-supplemented preservation solutions with low K+ (ECPEG) or high K+ (ICPEG) content. Animals autotransplanted with kidneys cold-stored for 24 h in ECPEG exhibited the greatest levels of creatinine clearance (Ccr: 161 +/- 12 mL/min, n=10) and the lowest levels of proteinuria (0.5 +/- 0.03 mg/mL) 16 weeks after surgery as compared with pigs autotransplanted with kidneys cold-stored in the other solutions tested (Ccr ranging from 80 and 140 mL/min). Similar differences, but with lower Ccr levels, were achieved after a prolonged period of cold-storage(48 h). ECPEG better preserved the kidneys from monocytes/macrophages and CD4+ T cells infiltrations, VCAM-1 and MHC class II overexpressions and occurrence of renal interstitial fibrosis (2%) as compared with the other preservation solutions (5%-20%). Adding the anti-ischemic drug trimetazidine (TMZ) to the preservation solutions, particularly ECPEG, further improved the quality of the week-16 post-transplanted kidneys (Ccr: 182 +/- 12 mL/min, n=10). These findings demonstrated that adding PEG to extracellular-like (with low K+ content) preservation solutions in combination with TMZ significantly improved the long-term outcome of kidney grafts in this model of autotransplanted pig kidney.


Assuntos
Transplante de Rim/métodos , Polietilenoglicóis/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Trimetazidina/farmacologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Temperatura Baixa , Fibrose/metabolismo , Taxa de Filtração Glomerular/efeitos dos fármacos , Sobrevivência de Enxerto , Imuno-Histoquímica , Rim/metabolismo , Rim/patologia , Preservação de Órgãos/métodos , Soluções para Preservação de Órgãos , Potássio/química , Potássio/metabolismo , Traumatismo por Reperfusão/terapia , Solventes/farmacologia , Suínos , Linfócitos T/metabolismo , Fatores de Tempo
18.
Nephrol Dial Transplant ; 19(7): 1742-51, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15128878

RESUMO

BACKGROUND: The renal medulla is particularly sensitive to oxidant stress and to ischaemia-reperfusion injury (IRI). In organ transplantation, delayed graft function is an important problem and cold ischaemia is thought to be the most important factor in short- and long-term complications. Our aim was to study cold-induced damage in proximal tubular segments and renal medulla osmolite excretion during use of various preservation solutions, and to clarify the role of trimetazidine (TMZ) in limiting renal dysfunction. METHODS: Using an autotransplanted pig kidney model, we assessed renal tubule function, medullary osmolite excretion and renal damage between day 1 and week 2 after 24 or 48 h cold storage in University of Wisconsin solution (UW), Celsior and ECPEG (two new high Na(+) preservation solutions) or the Hopital Edouard Herriot solution (HEH; a high Na(+) version of UW). In additional groups, TMZ was added to these preservation solutions for 24 and 48 h cold storage. RESULTS: Renal function was reduced under these preservation conditions. Tubular injury was associated with aminoaciduria and with a limited Na(+) reabsorbtion. Medullary damage led to the early appearance of trimethylamine-N-oxide and dimethylamine in urine. However, renal damage was modulated by preservation conditions. In addition, TMZ added to each of the solutions efficiently protected against IRI even after prolonged preservation. CONCLUSION: TMZ efficiently protected kidneys against damage when added to the HEH and particularly ECPEG solutions, even after 24 h cold storage. These findings point to a role for drugs that target mitochondria, and demonstrate that TMZ may provide a valuable therapeutic tool against IRI and could be included in therapeutic protocols.


Assuntos
Medula Renal/irrigação sanguínea , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos/efeitos adversos , Polietilenoglicóis/farmacologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Cloreto de Sódio/farmacologia , Trimetazidina/farmacologia , Animais , Temperatura Baixa , Rim/patologia , Rim/fisiologia , Suínos , Fatores de Tempo
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