RESUMO
OBJECTIVE/BACKGROUND: In light of the methods generally used to assess the risk of venous thromboembolism (VTE), major vascular operations should be regarded as high risk procedures. Nevertheless, no principles for implementing and maintaining thromboprophylaxis have so far been developed. The aim of this study was to determine the frequency and nature of VTE occurrence in patients routinely applying pharmacological thromboprophylaxis following implantation of an aorto-bifemoral prosthesis. METHODS: The prospective non-randomized study included 105 patients with aortoiliac obstruction and 119 patients with abdominal aortic aneurysm (AAA) treated surgically. During hospitalization pharmacological thromboprophylactic procedures were observed. A duplex test was performed on the day before surgery, on the day of discharge, and 30 days after the patients had left the hospital. RESULTS: VTE was detected in 18.1% of the patients with aortoiliac obstruction (9.5% of patients during hospitalization and 8.6% of patients after discharge). VTE was diagnosed in 21.0% of patients with AAA (15.1% of patients during hospitalization and 5.9% of patients after discharge). The incidence of VTE was comparable in both groups, both during hospitalization (p = .51) and in the 30 day period following the end of hospitalization (p = .48). It is advisable that before hospital discharge routine duplex ultrasonography tests should be conducted on the venous systems of all patients who have undergone major vascular operations. CONCLUSIONS: It is likewise advisable to consider whether thromboprophylaxis for vascular patients should be extended beyond their discharge from hospital.
Assuntos
Anticoagulantes/administração & dosagem , Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Arteriopatias Oclusivas/cirurgia , Implante de Prótese Vascular/efeitos adversos , Fibrinolíticos/administração & dosagem , Artéria Ilíaca/cirurgia , Tromboembolia Venosa/prevenção & controle , Idoso , Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico , Arteriopatias Oclusivas/diagnóstico , Esquema de Medicação , Inibidores do Fator Xa/administração & dosagem , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Incidência , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Polônia/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologiaRESUMO
AIM: Ovarian cancer (OC) is associated with a high risk of venous thromboembolism (VTE) in both, pre- and postoperative period. The aim of the study was to analyse the efficacy and the safety of an early prophylaxis with dalteparin in patients with OC qualified to surgery. METHODS: The prospective, non-randomized study was performed in the group of OC patients qualified to surgical treatment. The study group (SG) consisted of 37 patients with OC in whom thromboprophylaxis was started at the moment of qualification to the surgery (mean 16,1 days ± 11,32 SD before procedure). The control group (CG) consisted of 61 patients with OC qualified to surgery in whom thromboprophylaxis was started 12 hour before surgical treatment. The duration of postoperative prophylaxis was 4 weeks in both groups. Dalteparin 5000 U/day was used in both groups. The primary end points were occurrence of VTE and major bleeding. The patients underwent color Doppler US and D-dimer (DD) assessment at the moment of qualification for surgery, 1 day before and 7, 14, 28 days and 3 months after procedure. RESULTS: The total duration of thromboprophylaxis was 45.3 ± 10.7 days in SG and 27.9 ± 3.7 days in CG (P < 0.0001). The deep venous thrombosis rate was 2,7% in SG and 16.4% in CG (P = 0.042). Neither pulmonary embolism, nor major bleeding were observed. Median preoperative DD concentration in all patients was 1700 ng/ml and was significantly higher in patients who developed postoperative DVT when compared to those who did not, 2556.8 and 1691.0 ng/mL respectively (P = 0.0009). CONCLUSION: Prolonged preoperative thromboprophylaxis with dalteparin in patients with ovarian cancer qualified to the surgical treatment is safe, decreases the risk of thromboembolic complications. To determine indication, dosage and timing of such thromboprophylaxis in this group of patients further studies are required.
Assuntos
Anticoagulantes/administração & dosagem , Dalteparina/administração & dosagem , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Neoplasias Ovarianas/cirurgia , Tromboembolia Venosa/prevenção & controle , Adulto , Anticoagulantes/efeitos adversos , Biomarcadores/sangue , Dalteparina/efeitos adversos , Esquema de Medicação , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemorragia/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologiaRESUMO
OBJECTIVE: To show that adequate therapy for lymphoedema is able to restore ability to work. MATERIALS AND METHODS: The population of patients with primary lymphoedema registered in the university clinical centre diagnosed with primary or secondary lymphoedema and presumed by the national social institution as completely unable to work was selected for the retrospective analysis and divided into two groups. Group 1 consisted of 25 patients treated with a complex decongestive therapy programme daily for 3-6 weeks. The study population comprised 19 women and six men from 14 to 61 years of age (mean 31.5). In all 25 patients, complete inability to work was certified by the social institution before the treatment started. Group 2 consisted of 47 patients, 14 men and 33 women, aged from 26 to 71 years (mean 39 years) treated by so-called standard methods, who resigned from the proposed intensive treatment. In all 47 patients, complete inability to work was declared by the social institution before the treatment. Ability to work and oedema reduction were assessed by the treating physician. RESULTS: The intensive phase of treatment succeeded in 3870-15,330 mL oedema reduction in Group 1. After the end of therapy, 21 patients were able to work or study without any limitation and patients returned to their regular professional activity. Among four others, two were on welfare for at least 10 years, for another one welfare was their only income and one person was receiving a social pension. In none of the patients from group 2 was any significant oedema reduction observed. Every patient from group 2 maintained the social pension due to ineffective treatment. CONCLUSIONS: Complex decongestive therapy is a very efficient form of treatment in advanced primary and secondary lymphoedema. It allows returning to work after a short period of temporary disability without the necessity of a social pension.
Assuntos
Dispositivos de Compressão Pneumática Intermitente , Linfedema/terapia , Modalidades de Fisioterapia , Adolescente , Adulto , Idoso , Bandagens Compressivas , Drenagem , Feminino , Humanos , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To evaluate the relationship between the biomechanical properties and the structure of elastic components in different veins used for vascular reconstruction. DESIGN: In vitro experimental study. MATERIAL AND METHODS: Groups of 30 samples of incompetent saphenous veins (rSV), competent saphenous veins (cSV) and femoral veins (FVs) were compared following immunohistochemical staining for the presence of collagen types I, III and IV and elastin. The percentage area of transverse section of veins occupied by each type of collagen and elastin was measured using a computer-image-analysis system connected to a microscope. For all three groups of veins, the storage modulus, E', and the loss modulus, E'', were measured with a mechanical analyser, DMA-242, and changes in the function of temperature and frequency, and duration of exposure to the applied force were determined. RESULTS: The rSV showed the highest percentage share of collagen I and the lowest percentage share of collagen IV. These samples also showed the greatest expression of elastin and the highest elastin to collagen ratio. The rSV were also found to have the highest E' and E'', and during the long-term exposure achieved maximum stiffness in the least time as compared to cSV and FV. CONCLUSION: The histological structure directly influences the biomechanical properties of venous wall with rSV showing least compliance and cSV the greatest compliance.
Assuntos
Veia Femoral/transplante , Colágenos Fibrilares/metabolismo , Veia Safena/transplante , Adulto , Idoso , Fenômenos Biomecânicos , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Colágeno Tipo IV/metabolismo , Elasticidade , Elastina/metabolismo , Feminino , Veia Femoral/metabolismo , Veia Femoral/patologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica , Veia Safena/metabolismo , Veia Safena/patologiaRESUMO
OBJECTIVE: The aim of study was to assess how the ultrastructure of the wall of aortic aneurysms, sac and neck influences aortic wall distensibility and proximal dilatation 2 years after open repair. METHODS: Biopsies for electron microscopy were taken from aneurysmal sac and neck of 30 patients. Patients were assessed by computed tomography (CT) and ultrasound for aneurysm diameter and distensibility (M-mode ultrasonography). RESULTS: Postoperative CT of the aortic stump distinguished two groups. Group I (n = 11) with little enlargement, median 1 mm (1-3 mm) and group II (n = 19) with significant aortic enlargement, median 5.2 mm (4-12 mm). In group II, changes in elastic fibres in the aneurysm neck were comparable to, but as extreme as in the aneurysm sac. For group I, the distensibility of the aneurysmal sac was significantly lower than in the neck or at the renal arteries. For group II, the distensibility in both the neck and sac was significantly lower than at the juxtarenal segment (p = 0.01). The biopsies of group II patients showed the extensive degeneration of normal architecture, which was associated with altered wall distensibility in both the aneurysmal neck and sac. CONCLUSIONS: Disorganisation and destruction of normal aortic architecture at the ultrastructural level are associated with decreasing aortic distensibility. Low aortic neck distensibility is associated with proximal aortic dilatation at 2 years postoperatively.
Assuntos
Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/ultraestrutura , Aneurisma da Aorta Abdominal/fisiopatologia , Elasticidade , Endotélio Vascular/patologia , Endotélio Vascular/ultraestrutura , Humanos , Masculino , Pessoa de Meia-Idade , Grau de Desobstrução Vascular/fisiologiaRESUMO
BACKGROUND: Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution. METHODS: Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (microg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected. RESULTS: LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/microL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-alfa, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2+/-5.9; LPS 0.01, 38.9+/-11.6; LPS 0.1, 43.0+/-5.9; LPS 1.0, 46.6+/-11.3; Control, 14.5+/-9.8; p<0.0005 for all LPS vs. Control). CONCLUSIONS: The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV. LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-alfa, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.
Assuntos
Soluções para Diálise/metabolismo , Diálise Peritoneal , Peritonite/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Análise de Variância , Animais , Citocinas/metabolismo , Lipopolissacarídeos , Masculino , Peritônio/metabolismo , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
Recent studies suggest that peritoneal CD4(+) T lymphocytes may control recruitment of polymorphonuclear leukocytes (PMN) during peritonitis by an interleukin-17 (IL-17)-dependent mechanism. IL-17 and granulocyte colony-stimulating factor (G-CSF) have been proposed to form an axis that regulates PMN transmigration. Here we report on the role of G-CSF released by human peritoneal mesothelial cells (HPMCs) in IL-17A-mediated peritoneal PMN accumulation. In vitro exposure of HPMCs to IL-17A resulted in a time- and dose-dependent release of G-CSF. This effect was related to the induction of G-CSF mRNA and mediated through the nuclear factor-kappaB (NF-kappaB) pathway. The novel observation was that IL-17A-stimulated NF-kappaB activation in HPMCs followed a biphasic profile, with an early induction (45 min), followed by the return to basal levels (90 min), and a delayed induction (3 h). Tumor necrosis factor alpha synergistically amplified IL-17A-induced G-CSF production by enhanced NF-kappaB activation and through stabilization of G-CSF mRNA. Intraperitoneal (i.p.) administration of IL-17A in Balb/c mice resulted in increased local levels of G-CSF and selective PMN accumulation. Administration of anti-G-CSF blocking antibody before IL-17A injection significantly reduced the IL-17A-triggered PMN infiltration. This effect occurred despite increased i.p. levels of PMN-specific chemokines KC and macrophage inflammatory protein-2 seen in animals treated with anti-G-CSF antibody. These data demonstrate that the mesothelium-derived G-CSF plays an important role in IL-17A-induced PMN recruitment into the peritoneum.
Assuntos
Movimento Celular/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/metabolismo , Interleucina-17/farmacologia , Neutrófilos/citologia , Peritônio/citologia , Peritônio/metabolismo , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Epitélio , Regulação da Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/fisiologia , Neutrófilos/efeitos dos fármacos , Peritônio/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVE: The purpose of this study was to analyze the influence of cryopreservation on changes in diameter and compliance of allografts. METHODS: Sixty aortic allografts implanted in situ in rats were analyzed. The animals were divided into four groups that received fresh or cryopreserved isogenic (Lewis to Lewis) grafts, or fresh or cryopreserved allogenic (Lewis to DA) grafts, respectively. The diameter and compliance of the grafts were then visually evaluated with the digital video camera recorder after 15, 30, 60, 90 and 120 days. RESULTS: Gradual increase in diameter and decrease in compliance in case of all allogenic and cryopreserved isogenic grafts were observed. The observed changes in cryopreserved grafts were smaller when compared with fresh grafts, however, the differences did not reach statistical significance. CONCLUSION: Cryo preservation does not protect allografts from stiffening and dilatation.
Assuntos
Aorta Abdominal/patologia , Complacência (Medida de Distensibilidade) , Criopreservação , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/transplante , Núcleo Celular/metabolismo , Proliferação de Células , Fibroblastos/metabolismo , Macrófagos/metabolismo , Masculino , Modelos Animais , Miócitos de Músculo Liso/metabolismo , Ratos , Linfócitos T/metabolismo , Transplante Homólogo , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Túnica Média/metabolismo , Túnica Média/patologiaRESUMO
BACKGROUND: Hyaluronan (HA) is a major component of interstitial tissue that participates in fluid homeostasis, response to inflammation, and wound healing. Previous studies have shown that intraperitoneal administration of HA can affect peritoneal fluid transport during short peritoneal dialysis exchanges in anesthetized rats. We sought to investigate the effect of high molecular weight HA on peritoneal permeability in conscious rats during dialysis exchanges up to 8 hours in duration. In addition, we sought to investigate the absorption of HA from the peritoneal cavity, its accumulation in peritoneal tissues, and its metabolism in normal and uremic rats. METHODS: Experiments were performed on male Wistar rats infused with 30 mL peritoneal dialysis solution (Dianeal, Baxter Healthcare; Castelbar, Ireland) containing 10 mg/dL HA or with Dianeal alone (control). Peritoneal fluid removal (net ultrafiltration), permeability to glucose, creatinine, and total proteins, and tissue and blood levels of HA were determined in separate groups of rats at 1,2, 4, 6, and 8 hours after intraperitoneal infusion. Hyaluronan appearance and disappearance from plasma were also studied for 24 hours in separate groups of normal and uremic rats. RESULTS: Net ultrafiltration was significantly greater (27%) in rats infused with HA at 4, 6, and 8 hours (p < 0.01) compared to controls. Transperitoneal equilibration of protein was reduced by 27% (p < 0.001) at 4 hours and by 30% (p < 0.01) at 8 hours. During the 8-hour exchange, peritoneal clearance of creatinine increased by 27% (p < 0.01), whereas the clearance of total protein decreased by 27% (p < 0.005). After 8 hours, 25.7% +/- 3.1% of the administered HA was absorbed from the peritoneal cavity, peritoneal tissue HA concentration was increased by 117% (p < 0.001), and plasma HA levels increased by 435% (p < 0.001). Plasma HA levels returned to normal within 24 hours after intraperitoneal administration in both healthy and uremic rats. CONCLUSIONS: Hyaluronan added to dialysis fluid is absorbed from the peritoneal cavity and accumulates in peritoneal tissues. Hyaluronan supplementation produces changes in peritoneal permeability, leading to higher net ultrafiltration and peritoneal creatinine clearance, whereas total protein clearance decreases. The HA that is absorbed from the peritoneal cavity appears to be rapidly metabolized in both healthy and uremic rats.
Assuntos
Líquido Ascítico/metabolismo , Ácido Hialurônico/farmacologia , Diálise Peritoneal , Peritônio/metabolismo , Absorção , Animais , Creatinina/metabolismo , Soluções para Diálise/administração & dosagem , Glucose/metabolismo , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/farmacocinética , Infusões Parenterais , Masculino , Peritônio/efeitos dos fármacos , Permeabilidade , Proteínas/metabolismo , Ratos , Ratos Wistar , Uremia/metabolismoRESUMO
BACKGROUND: Peritoneal dialysis causes the functional and morphological changes in the peritoneum that result from the bioincompatibility of dialysis solutions. We present a model of chronic peritoneal dialysis in the rat that can be used for testing the biocompatibility of dialysis fluids. Methods and Results. Long-term exposure of the peritoneum to dialysis solutions can be performed in rats with implanted peritoneal catheters. Sampling of the dialysate allows the evaluation of intraperitoneal inflammation by examining cell differential and dialysate cytokine levels. Peritoneal permeability can be evaluated at designed time intervals with the peritoneal equilibration test (PET). At the end of dialysis, peritoneal histology is studied with light and electron microscopy. CONCLUSIONS: Such a multidirectional approach is an effective way to test biocompatibility of dialysis solutions.
Assuntos
Materiais Biocompatíveis/farmacologia , Soluções para Diálise/farmacologia , Diálise Peritoneal , Peritônio/efeitos dos fármacos , Animais , Cateteres de Demora , Soluções para Diálise/efeitos adversos , Masculino , Microscopia Eletrônica , Peritônio/metabolismo , Peritônio/patologia , Peritonite/induzido quimicamente , Peritonite/patologia , Permeabilidade , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: Heparin has anti-inflammatory effects and is often added to the peritoneal dialysis fluid to prevent fibrin formation. Conjugation of heparin to the surface of biomaterials has been shown to improve its biocompatibility. In this study, we describe for the first time an experimental chronic peritoneal dialysis model with repeated dwell studies in non-uraemic rats and evaluate the effect of addition of heparin to glucose-based peritoneal dialysis fluid on peritoneal fluid and solute transport. METHODS: Wistar male rats, weighing 340+/-15 g, with implanted peritoneal catheters were infused during 1 month, twice per day with 20 ml of Dianeal 1.36%+antibiotics (AB; n = 10) or Dianeal 1.36%+antibiotics+heparin 2500 U/l (HAB; n = 9). After 10 (DS 1) and 30 days (DS 2), a dwell study was performed in rats with free access to drinking water, by infusing 30 ml of Dianeal 3.86%. Dialysate samples were obtained at 0, 2, 30, 60, 120 and 240 min. Blood samples were drawn before and at the end of the dwell. Radiolabelled serum albumin was used as macromolecular volume marker. RESULTS: Peritoneal volumes during DS 1 were significantly greater for the HAB group as compared with the AB group. No differences in ultrafiltration were found during DS 2 for HAB vs AB. However, peritoneal volumes were significantly higher for DS 2 compared with DS 1 in the AB group. The amount of glucose absorbed over time did not differ between the solutions, while fluid absorption tended to be lower in the HAB group. CONCLUSIONS: Heparin may improve peritoneal fluid transport possibly due to better healing and reduced peritoneal inflammation as shown in this novel animal model of chronic peritoneal dialysis with repeated dwell studies.
Assuntos
Anti-Inflamatórios/administração & dosagem , Heparina/administração & dosagem , Diálise Peritoneal , Peritônio/metabolismo , Absorção/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Líquido Ascítico/metabolismo , Transporte Biológico/efeitos dos fármacos , Soluções para Diálise/farmacologia , Glucose/farmacocinética , Heparina/uso terapêutico , Injeções Intraperitoneais , Masculino , Ratos , Ratos Wistar , Soluções , Fatores de TempoRESUMO
BACKGROUND: We evaluated the effect of icodextrin on peritoneal permeability and inflammation in an experimental chronic peritoneal dialysis (PD) model with repeated dwell studies (DSs) in non uremic rats. METHODS: Male Wistar rats with implanted peritoneal catheters were infused twice daily for 3 weeks with 20 mL Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) (n = 11) or icodextrin 7.5% (n = 12). After 10 days (DS1) and 21 days (DS2), a 4-hour DS using 30 mL icodextrin solution was performed in conscious animals. Radioiodinated serum albumin (RISA) was used as a macromolecular volume marker. Blood samples were drawn before the start of the dwell and at its end. RESULTS: We observed a steady increase in intraperitoneal volume (IPV) versus dwell time (0-240 minutes) during DS1 and DS2 in both groups. No significant differences in peritoneal permeability to solutes were observed between the groups. However, in both groups, IPV volume was significantly higher during DS2 after the 4-hour dwell time [IPV icodextrin: 34.4 +/- 1.4 mL (DS1), 35.4 +/- 1.1 mL (DS2), p < 0.002; IPV Dianeal: 34.2 +/- 0.9 mL (DS1), 35.2 +/- 0.7 mL (DS2), p < 0.01]. CONCLUSION: Changes of peritoneal permeability seen during in vivo experimental models of chronic peritoneal dialysis in rats with repeated dwell studies are comparable to results obtained in humans on continuous ambulatory peritoneal dialysis (CAPD).
Assuntos
Soluções para Diálise/farmacologia , Glucanos/farmacologia , Glucose/farmacologia , Diálise Peritoneal , Peritônio/metabolismo , Animais , Transporte Biológico , Icodextrina , Masculino , Permeabilidade , Compostos Radiofarmacêuticos , Ratos , Ratos Wistar , Soroalbumina RadioiodadaRESUMO
BACKGROUND: Glucose is still used as an osmotic solute in peritoneal dialysis fluids, despite evidence of its local (peritoneal) and systemic toxicities. However a constant search is underway for a new, more biocompatible osmotic solute for peritoneal dialysis fluids. OBJECTIVE: The present study evaluated N-acetylglucosamine (NAG) in a concentration of 220 mmol/L as an alternative to glucose for the osmotic solute in peritoneal dialysis fluid, during chronic peritoneal dialysis in rats. METHODS: For 8 weeks, male Wistar rats were infused with glucose-based or NAG-based dialysis fluid. Intraperitoneal inflammation and peritoneal permeability and morphology were evaluated in all rats during the study. RESULTS: Repeated intraperitoneal infusion of the NAG-based dialysis fluid resulted in a weaker intra-abdominal inflammatory reaction as compared with the reaction in rats infused with glucose-based dialysis solution. At the end of the study, the concentration of hyaluronan in the peritoneal interstitium obtained from NAG-treated rats was higher than that found in the interstitium taken from animals exposed to dialysis fluid containing glucose. Also, peritoneal permeability to total protein was lower in NAG-treated rats. CONCLUSION: As an alternative to glucose, NAG used for the osmotic solute in peritoneal dialysis solution decreases the intraperitoneal inflammatory reaction induced by the process of peritoneal dialysis and, indirectly (owing to the increased hyaluronan content in the peritoneal interstitium), diminishes peritoneal permeability to protein.
Assuntos
Acetilglucosamina , Soluções para Diálise/química , Glucose , Diálise Peritoneal , Animais , Contagem de Células , Quimiocina CCL2/análise , Macrófagos , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/análiseRESUMO
IL-17 is a newly discovered cytokine implicated in the regulation of hemopoiesis and inflammation. Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyte infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene alpha (GROalpha). Pretreatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROalpha mRNA and protein. Combination of IL-17 together with TNF-alpha resulted in an increased stability of GROalpha mRNA and synergistic release of GROalpha protein. Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo. IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.
Assuntos
Quimiocinas CXC/metabolismo , Fatores Quimiotáticos/metabolismo , Substâncias de Crescimento/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular , Interleucina-17/fisiologia , Infiltração de Neutrófilos/imunologia , Peritônio/citologia , Peritônio/imunologia , Animais , Células Cultivadas , Quimiocina CXCL1 , Fatores Quimiotáticos/biossíntese , Fatores Quimiotáticos/genética , Fatores Quimiotáticos/imunologia , Cicloeximida/farmacologia , Dactinomicina/farmacologia , Epitélio/imunologia , Epitélio/metabolismo , Substâncias de Crescimento/biossíntese , Substâncias de Crescimento/genética , Substâncias de Crescimento/imunologia , Humanos , Soros Imunes/administração & dosagem , Injeções Intraperitoneais , Interleucina-17/administração & dosagem , Interleucina-17/antagonistas & inibidores , Interleucina-17/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peritônio/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/imunologia , RNA Mensageiro/metabolismo , Receptores de Interleucina/biossíntese , Receptores de Interleucina-17 , Proteínas Recombinantes/biossíntese , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/imunologia , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
BACKGROUND: Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. METHODS: Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. RESULTS: After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P < 0.003; 33% lower for total protein, P < 0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P < 0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 +/- 22.8 +/- 9.5%, P < 0.01) and lower levels of the cytokines, tumor necrosis factor-alpha (11.2 +/- 14.7 vs. 42.3 +/- 35.3 pg/mL, P < 0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 +/- 86.5 vs. 402.4 +/- 258.3 pg/mL, P < 0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P < 0.01) than tissue from control animals. CONCLUSIONS: The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.
Assuntos
Soluções para Diálise , Ácido Hialurônico/administração & dosagem , Peritônio/metabolismo , Peritonite/metabolismo , Animais , Biomarcadores , Citocinas/análise , Soluções para Diálise/química , Ácido Hialurônico/metabolismo , Ácido Hialurônico/farmacologia , Masculino , Diálise Peritoneal , Peritônio/efeitos dos fármacos , Peritônio/patologia , Permeabilidade/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
OBJECTIVE: To compare effects of N-acetylglucosamine (NAG)-based and glucose-based dialysis fluids on the function of peritoneal leukocytes in conditions of peritoneal dialysis. DESIGN: In vitro experiments on ex vivo isolated rat peritoneal leukocytes. MATERIALS: Peritoneal leukocytes were isolated from rats on chronic peritoneal dialysis. On alternate days, fluid exchanges were performed with NAG-based or glucose-based dialysis solutions. After a 4-hour dwell, dialysate was drained and peritoneal leukocytes were incubated in vitro +/- lipopolysaccharide (LPS). Production of nitrites (index of NO synthesis), tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and interferon gamma (IFN-gamma) by unstimulated or stimulated peritoneal leukocytes originating from NAG-based or glucose-based fluid was measured. RESULTS: Dialysate cell count was lower during exchanges with NAG-based fluid (2113+/-615 cells/microL) as compared to glucose-based fluid (3643+/-1108 cells/microL; p < 0.01). Differential cell count was similar in both studied groups. Unstimulated peritoneal leukocytes from NAG-based dialysate produced more NO (nitrites) (0.65+/-0.07 micromol per 10(6) cells) than did cells from glucose-based dialysate (0.26+/-0.09 micromol per 106 cells, p < 0.01). Stimulated peritoneal leukocytes from NAG-based dialysate produced more cytokines than did cells from glucose-based dialysate: TNFalpha, 135.2+/-37.0 pg versus 70.2+/-21.8 pg per 10(6) cells respectively, p < 0.01; IL-1beta, 143.2+/-60.9 pg versus 99.1+/-22.4 pg per 10(6) cells respectively, p < 0.05; IFN-gamma, 16.2+/-12.5 pg versus 6.0+/-1.8 pg per 10(6) cells respectively, p < 0.01. CONCLUSIONS: We demonstrated that rat peritoneal leukocytes exposed in vivo to NAG-based dialysis fluid have better ability to produce inflammatory mediators than do peritoneal leukocytes from the same donor, but exposed in vivo to glucose-based dialysis solution.
Assuntos
Acetilglucosamina/farmacologia , Leucócitos/efeitos dos fármacos , Cavidade Peritoneal/citologia , Diálise Peritoneal , Animais , Contagem de Células , Células Cultivadas , Soluções para Diálise/farmacologia , Glucose/farmacologia , Interferon gama/biossíntese , Interleucina-1/biossíntese , Contagem de Leucócitos , Leucócitos/metabolismo , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/biossínteseRESUMO
OBJECTIVE: To assess the in vivo peritoneal inflammatory reaction in rats dialyzed with neutral, bicarbonate-lactate-buffered dialysis fluid. METHODS: Chronic peritoneal dialysis was performed for 4 weeks in Wistar rats with two solutions: (1) 40 mmol/L lactate-buffered fluid, pH 5.2, with a glucose concentration of 2.27 g/dL (Lac); and, (2) 15 mmol/L lactate and 25 mmol/L bicarbonate-buffered fluid, pH 7.0-7.5, with a glucose concentration of 2.27 g/dL (Bic-Lac). After 4 weeks, two peritoneal equilibration tests (PET 1 and PET 2) were performed in all animals with each respective solution. PET 1 was done with test solutions alone, whereas, on a subsequent day, PET 2 was performed with test solutions supplemented with endotoxin [lipopolysaccharide (LPS)] to induce peritonitis. RESULTS: During PET 1 no consistent differences were detected in peritoneal permeability between the Lac and Bic-Lac groups. Total dialysate cell count in the Bic-Lac animals was lower than in rats treated with Lac fluid: that is, at 8 hours, the respective counts were 1858+/-524 cells/microL versus 2785+/-1162 cells/microL (p < 0.01). Dialysate from animals dialyzed with Bic-Lac contained more macrophages (at 4 hours: 53.6%+/-35.8% versus 35.8%+/-8.8%, p < 0.001) and fewer neutrophils (at 4 hours: 3.6%+/-1.8% versus 15.4%+/-6.1%, p < 0.001) as compared to those dialyzed with the Lac solution. Concentration of nitrites in 8-hour dwell dialysate samples from Bic-Lac rats was lower than that in the Lac group (0.98+/-0.28 micromol/mL versus 2.32+/-0.87 micromol/mL, p < 0.002), but cytokine levels in the dialysates were comparable. During PET 2, the increase in peritoneal permeability resulting from the LPS-induced inflammatory response was similar for both test solutions. Dialysate cell count was higher in the Lac group versus the Bic-Lac group (at 8 hours: 8789+/-4862 cells/microL versus 3961+/-581 cells/microL, p < 0.001), contained more neutrophils (at 8 hours: 80.0%+/-11.3% versus 54.8%+/-4.4%, p < 0.001) and fewer macrophages (at 8 hours: 6.8%+/-5.6% versus 21.2%+/-3.3%, p < 0.05). During peritonitis, we found a higher overall dialysate concentration of both tumor necrosis factor (TNFalpha: +53%, p < 0.05) and of interferon gamma (IFN-gamma: +303%, p < 0.02), in the Bic-Lac group than in the Lac group. CONCLUSIONS: A lower dialysate cell count, higher percentage of macrophages, and lower percentage of neutrophils in dialysate suggest that Bic-Lac fluid induces a diminished nonspecific inflammatory response of the peritoneal cavity during dialysis. However, after in vivo stimulation, peritoneal cells from animals dialyzed with Bic-Lac solution possess an augmented ability to produce inflammatory cytokines.
Assuntos
Bicarbonatos/farmacologia , Soluções para Diálise/química , Soluções para Diálise/farmacologia , Ácido Láctico/farmacologia , Diálise Peritoneal , Peritônio/metabolismo , Peritonite/metabolismo , Animais , Contagem de Células , Creatinina/metabolismo , Citocinas/metabolismo , Glucose/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Macrófagos/citologia , Masculino , Neutrófilos/citologia , Nitritos/metabolismo , Peritônio/citologia , Peritonite/etiologia , Permeabilidade , Proteínas/metabolismo , Ratos , Ratos WistarRESUMO
In order to help sick persons with making an aware decision to undergo a surgical treatment it is necessary to instruct them in every possible aspect of the proposed therapy. Aiming at adjusting the range and form of information to individual case of each patient, we have tried to estimate his/her general medical awareness and the extent of the acquirement of information received. On the ground of analysis of the results, it was found that 20-50% of patients had no basic knowledge of their illness at the moment of their admission to the hospital. Although 67% of the patients were satisfied with the questionnaire and preoperative explanation, every other patient had no understanding of the essence of the medical action planned. At the same time, about 50% of the patients declared a possibility of withdrawing their consent to surgical treatment, if given more comprehensive information about possible complications.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Consentimento Livre e Esclarecido , Educação de Pacientes como Assunto/estatística & dados numéricos , Cuidados Pré-Operatórios , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Satisfação do Paciente , Polônia , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/psicologia , Avaliação de Programas e Projetos de Saúde , Inquéritos e QuestionáriosRESUMO
Anephric rats were maintained on continuous ambulatory peritoneal dialysis (CAPD). Peritoneal permeability was assessed during a standard 4-hour peritoneal equilibration test (PET) performed with Dianeal 3.86% (Baxter Healthcare, Deerfield, Illinois, U.S.A.). The effect of uremia on peritoneal permeability was evaluated in an experimental protocol in which each animal served as its own control. In each rat, PET1 (control) was performed before removal of kidneys and PET2 (uremia) was performed four days after removal of kidneys. Net ultrafiltration during a 4-hour exchange with Dianeal 3.86% was higher during PET1 (3.8 +/- 2.3 mL) than during PET2 (-1.3 +/- 3.3 mL), p < 0.05. Peritoneal permeability to urea and glucose was similar in both series. Transperitoneal equilibration of creatinine concentration was faster in uremic animals: D/P at 4 hours was 0.94 +/- 0.06 during PET2 versus 0.77 +/- 0.08 during PET1, p < 0.001. The opposite difference was seen for total protein: D/Px 1000 after a 4-hour dwell was 51.4 +/- 19.8 during PET2 versus 70.3 +/- 12.9 during PET1, p < 0.05. Our results show that uremia modifies the permeability of the peritoneum to both water and solutes.