RESUMEN
OBJECTIVE: Aim: To determine the effect of the developed complex treatment of patients with peritonitis on the dynamics of humoral factors of nonspecific reactivity in the course of the disease. PATIENTS AND METHODS: Materials and Methods: The study included 124 patients with toxic and terminal stages of peritonitis, who were divided into 3 groups. Group I (main) included 39 patients whose complex treatment included cytochrome C. Group II (main) included 41 patients whose complex treatment included cytochrome C and a solution containing levocarnitine and arginine hydrochloride. The comparison group comprised 44 patients who did not receive the specified drugs. The patients underwent determination of the levels of fibronectin, ceruloplasmin, and procalcitonin in the serum during the course of the disease. RESULTS: Results: In patients of the I and II main groups, the use of the proposed treatment contributed to the optimization of the production of acute phase proteins: a decrease in procalcitonin production during the study, optimization of ceruloplasmin and fibronectin production, especially in the II main group. In patients of the comparison group, decompensation in the production of humoral inflammatory factors was determined, associated with a significant increase in fibronectin production, a decrease in ceruloplasmin content, and an increase in procalcitonin throughout the entire period. CONCLUSION: Conclusions: The use of cytochrome C and a solution containing levocarnitine and arginine hydrochloride in the complex treatment of patients with disseminated peritonitis helps to optimize the production of acute phase proteins, which leads to a decrease in inflammation and the preservation of factors of nonspecific humoral activity at a subcompensated level.
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Proteínas de Fase Aguda , Ceruloplasmina , Peritonitis , Polipéptido alfa Relacionado con Calcitonina , Humanos , Peritonitis/tratamiento farmacológico , Peritonitis/sangre , Femenino , Masculino , Persona de Mediana Edad , Ceruloplasmina/metabolismo , Proteínas de Fase Aguda/metabolismo , Polipéptido alfa Relacionado con Calcitonina/sangre , Fibronectinas/sangre , Citocromos c/sangre , Citocromos c/metabolismo , Periodo Posoperatorio , Arginina/sangre , Adulto , AncianoRESUMEN
Peritonitis is a common and life-threatening inflammatory disease. Myeloid cells are elevated in the peripheral blood and contribute to peritonitis, but their circulating dynamics are not clear. In vivo flow cytometry (IVFC) is a noninvasive technique for monitoring the dynamics of circulating cells in live animals. It has been extensively used to detect circulating tumor cells, but rarely for monitoring immune cells. Here, we describe a method adapting an intravital microscope for IVFC so that we can monitor LysM-EGFP-labeled circulating myeloid cells in a tumor necrosis factor (TNF) α-induced peritonitis mouse model. Using this IVFC method, we quantified the blood flow velocity and cell concentration in circulation. We observed a significant increase in LysM-EGFP+ cells in circulation after TNFα intraperitoneal (i.p.) injection, which reached a plateau in ~20 min. Conventional cytometry analysis showed that most LysM-EGFP+ cells were neutrophils. Increasing blood neutrophils were accompanied by neutrophil recruitment to the peritoneal cavity and neutrophil emigration from the bone marrow. We then monitored neutrophil CD64 expression in vivo and found a significant increase in TNFα-induced peritonitis. We also found that CD18 blockade doubled the circulating neutrophil number in TNFα-induced peritonitis, suggesting that CD18 is critical for neutrophil recruitment in peritonitis. Overall, we demonstrate that IVFC techniques are useful for studying the circulating dynamics of immune cells during inflammatory diseases.
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Citometría de Flujo , Células Mieloides , Peritonitis , Factor de Necrosis Tumoral alfa , Animales , Peritonitis/inducido químicamente , Peritonitis/sangre , Citometría de Flujo/métodos , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Células Mieloides/metabolismo , Neutrófilos/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Proteínas Fluorescentes Verdes/metabolismo , Proteínas Fluorescentes Verdes/genéticaRESUMEN
Background and Objectives: Spontaneous bacterial peritonitis (SBP) is a life-threatening disease that requires early diagnosis and treatment. It is known that a positive culture result for SBP, which is a common reason for admission to the emergency department, is related to the severity and prognosis of the disease. However, as it is not possible to determine the culture result in the early stage of the disease, different methods are required to predict prognosis in the emergency department. This study was conducted to evaluate the success of the SII, SIRI, NLR and PLR in predicting culture results, intensive care needs and mortality in patients with SBP admitted to the emergency department. Materials and Methods: This study was a retrospective, observational study. Patients with SBP who applied to the emergency department were included in this study. Pregnant women, patients with a malignancy, patients with another infection and patients with liver failure were excluded from this study. Data were analyzed in terms of culture results, the need for intensive care and mortality development. Analyses were performed using SPSS version 26. Results are presented with a 95% confidence interval. A p value less than 0.05 was considered statistically significant. Participant data were analyzed using the independent samples t-test or the Mann-Whitney U test based on normality, and ROC analyses were conducted to assess test accuracies and determine cut-off values. Results: A total of 275 patients were included in this study. Although the culture results of 183 patients were positive, 92 were negative. The SII, NLR and PLR were found to be significantly higher in culture-positive patients (p < 0.001, p = 0.013 and p = 0.002, respectively). The SII and NLR were found to be significantly higher in patients with high mortality (p < 0.001 and p = 0.017, respectively). Conclusions: This study showed that the SII, NLR and PLR may be useful in predicting culture positivity and prognosis in SBP patients in the emergency department.
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Servicio de Urgencia en Hospital , Linfocitos , Neutrófilos , Peritonitis , Humanos , Femenino , Estudios Retrospectivos , Masculino , Peritonitis/microbiología , Peritonitis/sangre , Peritonitis/inmunología , Persona de Mediana Edad , Pronóstico , Adulto , Anciano , Plaquetas , Valor Predictivo de las Pruebas , Infecciones Bacterianas/sangre , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/mortalidad , Curva ROC , Inflamación/sangreRESUMEN
PURPOSE: Peritoneal infection, due to anastomotic leakage, after resection for colorectal cancer have been shown to associate with increased cancer recurrence and mortality, as well as cardiovascsular morbidity. Alterations in circulating protein levels could help shed light on the underlying mechanisms, prompting this exploratory study of 64 patients operated for colorectal cancer with anastomosis. METHODS: Thirty-two cases who suffered a postoperative peritoneal infection were matched with 32 controls who had a complication-free postoperative stay. Proteins in serum samples at their first postoperative visit and at one year after surgery were analysed using proximity extension assays and enzyme-linked immunosorbent assays. Multivariate projection methods, adjusted for multiple testing, were used to compare levels between groups, and enrichment and network analyses were performed. RESULTS: Seventy-seven proteins, out of 270 tested, were differentially expressed at a median sampling time of 41 days postoperatively. These proteins were all normalised one year after surgery. Many of the differentially expressed top hub proteins have known involvement in cancer progression, survival, invasiveness and metastasis. Over-represented pathways were related to cardiomyopathy, cell-adhesion, extracellular matrix, phosphatidylinositol-3-kinase/Akt (PI3K-Akt) and transforming growth factor beta (TGF-ß) signaling. CONCLUSION: These affected proteins and pathways could provide clues as to why patients with peritoneal infection might suffer increased cancer recurrence, mortality and cardiovascular morbidity.
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Neoplasias Colorrectales , Humanos , Masculino , Femenino , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Anciano , Persona de Mediana Edad , Peritonitis/sangre , Peritonitis/cirugía , Peritonitis/etiología , Estudios de Casos y Controles , Fuga Anastomótica/sangre , Fuga Anastomótica/etiología , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Colectomía/efectos adversosRESUMEN
BACKGROUND: In the livestock industry, Foreign Body Syndrome is a devastating disease condition. Feeding management, lacking of food discrimination, and eating chopped food increase the risk of swallowing sharp foreign bodies in bovine species. In addition to the honeycomb cells shape of the reticulum, the contractions of the reticular wall, gravid uterine pressure, and parturition efforts, foreign bodies can penetrate the reticular wall, causing cascade of problems including traumatic reticulitis, traumatic reticuloperitonitis, and traumatic pericarditis. The present study was carried out to evaluate the diagnostic significance of cardiac troponin I rapid test cassette and other cardiac biomarkers including serum cardiac troponin I (cTn I), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase enzyme (AST), in confirmed cases of traumatic pericarditis (TP) and/or traumatic reticuleoperitonitis (TRP) in cattle and buffaloes. METHODS: A total number of 30 animals (22 cattle and 8 buffaloes) with different signs such as anorexia, jugular distension, brisket edema, and signs of pain (reluctance to move, arching back, and abduction of the forelimbs) were included in the present study. Based on case history, clinical signs, ferroscopic, pericardiocentesis, radiographic and ultrasonographic examinations, TP were confirmed in cattle (n = 10) and buffaloes (n = 8) while TRP were confirmed only in cattle (n = 12). Additionally, 20 clinically healthy animals (n = 10 cattle and 10 buffaloes) were used as a control group. Blood samples were collected for determination of blood level of Tn-I, and activity of CK-MB, LDH, and AST. RESULTS: The obtained results revealed a highly significant increase in serum cTn I in diseased cattle with TP and TRP (P = 0.00), while buffaloes with TP showed no significant changes in serum cTn I (P = 0.111). Both diseased cattle and buffaloes showed increased serum activities of CK-MB, AST, and LDH enzyme. On the other hand, cardiac troponin I rapid test cassette failed to detect cTn I in diseased animals. CONCLUSION: The study concluded that the cardiac troponin I rapid test cassette did not have a diagnostic significance and could not be used as a point-of-care under field condition for diagnosis of TP and TRP in large ruminants. However, the serum troponin I level is helpful in diagnosis of TP and TRP in cattle. Although cardiac biomarkers have some diagnostic values in TP and TRP, the traditional diagnostic methods (clinical, radiography and ultrasonography examinations) are crucial for thorough evaluation of TP/TRP cases in bovine.
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Biomarcadores , Búfalos , Enfermedades de los Bovinos , Forma MB de la Creatina-Quinasa , Pericarditis , Reticulum , Troponina I , Animales , Pericarditis/veterinaria , Pericarditis/diagnóstico , Pericarditis/sangre , Bovinos , Biomarcadores/sangre , Troponina I/sangre , Enfermedades de los Bovinos/diagnóstico , Enfermedades de los Bovinos/sangre , Forma MB de la Creatina-Quinasa/sangre , Femenino , Peritonitis/veterinaria , Peritonitis/diagnóstico , Peritonitis/sangre , L-Lactato Deshidrogenasa/sangre , Aspartato Aminotransferasas/sangre , Masculino , Cuerpos Extraños/veterinaria , Cuerpos Extraños/complicaciones , Cuerpos Extraños/diagnósticoRESUMEN
BACKGROUND: Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP. METHODS: A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure. RESULTS: Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure. CONCLUSIONS: This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.
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Fallo Renal Crónico , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Diálisis Peritoneal , Peritonitis , Humanos , Péptido Natriurético Encefálico/sangre , Masculino , Femenino , Diálisis Peritoneal/efectos adversos , Fragmentos de Péptidos/sangre , Persona de Mediana Edad , Peritonitis/etiología , Peritonitis/sangre , Estudios Retrospectivos , Factores de Riesgo , Fallo Renal Crónico/terapia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Insuficiencia del Tratamiento , Anciano , Adulto , Biomarcadores/sangreRESUMEN
ABSTRACT: Background : This study aimed to evaluate the effect of polymyxin B hemoperfusion (PMX-HP) in patients with peritonitis-induced septic shock who still required high-dose vasopressors after surgical source control. Methods : This retrospective study included adult patients admitted to the surgical intensive care unit (ICU) at Seoul National University Hospital between July 2014 and February 2021 who underwent major abdominal surgery to control the source of sepsis. Patients were divided into two groups based on whether PMX-HP was applied after surgery or not. The primary and secondary endpoints were the vasopressor reduction effect, and in-ICU mortality, respectively. Propensity score matching was performed to compare the vasopressor reduction effect. Results : A total of 338 patients met the inclusion criteria, of which 23 patients underwent PMX-HP postoperatively, whereas 315 patients did not during the study period. Serum norepinephrine concentration decreased over time regardless of whether PMX-HP was applied. However, it decreased more rapidly in the PMX-HP(+) group than in the PMX-HP(-) group. There were no significant differences in demographics including age, sex, body mass index, and most underlying comorbidities between the two groups. Risk factors for in-ICU mortality were identified by comparing patient characteristics and perioperative factors between the two groups using multivariate analysis. Conclusion : For patients with peritonitis-induced septic shock, PMX-HP rapidly reduces the requirement of vasopressors immediately after surgery but does not reduce in-ICU mortality. This effect could potentially accelerate recovery from shock, reduce sequelae from vasopressors, and ultimately improve quality of life after discharge.
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Hemoperfusión , Peritonitis , Polimixina B , Puntaje de Propensión , Choque Séptico , Vasoconstrictores , Humanos , Polimixina B/uso terapéutico , Choque Séptico/sangre , Choque Séptico/tratamiento farmacológico , Choque Séptico/terapia , Masculino , Femenino , Hemoperfusión/métodos , Peritonitis/tratamiento farmacológico , Peritonitis/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Vasoconstrictores/uso terapéutico , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: This study aims to investigate the potential correlation between baseline red cell distribution width (RDW) to albumin ratio (RAR) levels and treatment failure in peritoneal dialysis-associated peritonitis (PDAP) patients. METHODS: A retrospective single-center study was conducted on 286 PDAP patients. Logistic regression and generalized estimation equation (GEE) analyses were employed to assess the relationship between RAR and treatment failure. RESULTS: RAR emerged as a robust predictor of treatment failure in PDAP patients. Elevated RAR levels were associated with an increased risk of treatment failure, exhibiting a linear relationship. Even after adjusting for demographic and clinical variables, this association remained statistically significant. ROC analysis revealed that RAR outperformed RDW and albumin individually in predicting PDAP prognosis. CONCLUSION: This study highlights RAR as a superior prognostic marker for treatment failure in PDAP patients, offering new insights into risk assessment and management strategies for this challenging condition.
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Índices de Eritrocitos , Diálisis Peritoneal , Peritonitis , Albúmina Sérica , Insuficiencia del Tratamiento , Humanos , Femenino , Masculino , Estudios Retrospectivos , Peritonitis/etiología , Peritonitis/sangre , Persona de Mediana Edad , Diálisis Peritoneal/métodos , Diálisis Peritoneal/efectos adversos , Pronóstico , Albúmina Sérica/metabolismo , Albúmina Sérica/análisis , Anciano , Medición de Riesgo/métodos , Valor Predictivo de las Pruebas , Adulto , Biomarcadores/sangreRESUMEN
Objective: To observe the level and detection of ascites CD100 on the activity of CD4(+) and CD8(+) T lymphocytes in vitro in the peripheral blood of patients with liver cirrhosis combined with spontaneous bacterial peritonitis. Methods: Peripheral blood and ascites were collected from 77 cases of liver cirrhosis (49 patients with liver cirrhosis combined with simple ascites and 28 patients with liver cirrhosis combined with SBP), and peripheral blood was collected from 22 controls. Soluble CD100 (sCD100) in peripheral blood and ascites was detected by an enzyme-linked immunosorbent assay. Flow cytometry was used to detect membrane-bound CD100 (mCD100) on the surface of CD4(+) and CD8(+)T lymphocytes. CD4(+) and CD8(+)T lymphocytes in ascites were sorted. CD4(+)T lymphocyte proliferation, key transcription factor mRNA, and secreted cytokine changes, as well as CD8(+)T lymphocyte proliferation, important toxic molecule mRNA, and secreted cytokine changes, were detected after CD100 stimulation. The killing activity of CD8(+)T cells was detected by direct contact and indirect contact culture systems. Data conforming to normality were compared using one-way ANOVA, a student's t-test, or a paired t-test. Data that did not conform to a normal distribution were compared using either the Krusal-Willis test or the Mann-Whitney test. Results: There was no statistically significant difference in plasma sCD100 level between patients with liver cirrhosis combined simple ascites (1 415 ± 434.1) pg/ml, patients with liver cirrhosis combined with SBP (1 465 ± 386.8) pg/ml, and controls (1 355 ± 428.0) pg/ml (P = 0.655). The ascites sCD100 level was lower in patients with liver cirrhosis combined with SBP than that of patients with simple ascites [(2 409 ± 743.0) pg/ml vs. (2825±664.2) pg/ml, P=0.014]. There was no statistically significant difference in the level of mCD100 in peripheral blood CD4(+) and CD8(+) T lymphocytes among the three groups (P > 0.05). The levels of mCD100 in ascites CD4(+) and CD8(+) T lymphocytes were higher in patients with liver cirrhosis combined with SBP than those in patients with simple ascites (P < 0.05). CD100 stimulation had no significant effect on the proliferation of CD4(+) and CD8(+)T lymphocytes in the ascites of patients with liver cirrhosis combined with SBP (P > 0.05). There were no significant effects on the expression of transcription factors in effector CD4(+)T lymphocytes (T-bet, retinoic acid associated solitary nuclear receptor γt, aromatic hydrocarbon receptor) or secretion of cytokines (interferon-γ, 17, and 22) (P > 0.05). CD100 stimulation had increased the relative expression of perforin, granzyme B, and granlysin mRNA and the levels of secreted interferon-γ and tumor necrosis factor-α, killing activity in ascites CD8+ T lymphocytes of patients with liver cirrhosis combined with SBP (P < 0.05). Conclusion: The active form of CD100 is sCD100 instead of mCD100. There is an imbalance between the expression of sCD100 and mCD100 in the ascites of patients with cirrhosis combined with SBP. sCD100 can enhance the function of CD8(+)T lymphocytes in the ascites of patients with cirrhosis combined with SBP and thus is one of the potential therapeutic targets.
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Antígenos CD , Ascitis , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Cirrosis Hepática , Peritonitis , Ascitis/inmunología , Inmunomodulación/inmunología , Antígenos CD/sangre , Antígenos CD/inmunología , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Cirrosis Hepática/inmunología , Peritonitis/sangre , Peritonitis/complicaciones , Peritonitis/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , HumanosRESUMEN
Oxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial ß-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin ß-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-γ. Last, dampening oxylipin levels by ß-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial ß-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.
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Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Metabolismo de los Lípidos/genética , Mitocondrias/efectos de los fármacos , Oxilipinas/metabolismo , Peritonitis/genética , Sepsis/genética , Acil-CoA Deshidrogenasa de Cadena Larga/sangre , Acil-CoA Deshidrogenasa de Cadena Larga/genética , Animales , Carnitina O-Palmitoiltransferasa/sangre , Carnitina O-Palmitoiltransferasa/genética , Coenzima A Ligasas/sangre , Coenzima A Ligasas/genética , Femenino , Regulación de la Expresión Génica , Humanos , Recién Nacido , Interferón gamma/farmacología , Lipidómica/métodos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Subunidad beta de la Proteína Trifuncional Mitocondrial/sangre , Subunidad beta de la Proteína Trifuncional Mitocondrial/genética , Oxidación-Reducción , Peritonitis/sangre , Peritonitis/inducido químicamente , Peritonitis/patología , Células RAW 264.7 , Sepsis/sangre , Sepsis/patologíaRESUMEN
Bacterial peritonitis is a severe disease that diagnosis remains challenging for clinicians. Measuring biomarkers might be a rapid diagnostic method. The objective of this study was to analyze and evaluate the dynamic changes in HIF-1α concentration in serum exosomes during bacterial peritonitis. The pre-clinical application value of serum exosomal HIF-1α was evaluated via imipenem and cilastatin sodium (ICS) intervention in the bacterial peritonitis model. The new colorimetric method to quantitate dynamic expression changes of HIF-1α in serum exosomes during bacterial peritonitis was established by our team via using the gold seed-coated with aptamer-functionalized Au @ Au core-shell peroxidase mimic. The typical inflammatory cytokines of bacterial peritonitis were also measured. Following intramuscular administration with ICS, In-Vivo Xtreme imaging system was used to visualize abdominal infection extent. Meanwhile, HIF-1α concentration in rat serum exosomes and pro-inflammatory factors levels in serum were detected. The serum typical inflammatory cytokines levels were elevated in GFP-labeled E.coli induced bacterial peritonitis. The serum exosomal HIF-1α levels clearly increased at 12 h, reached the peak during 24-48 h, and then gradually decreased at 72 h. Following intramuscular administration with ICS, the abdominal infection extent, HIF-1α concentration in serum exosomes, and the serum pro-inflammatory factors levels were reduced at 24 h in GFP-labeled E. coli induced bacterial peritonitis model. The serum exosomal HIF-1α can be used as a biomarker in the early stage of bacterial peritonitis, which might provide the basic research in the pre-clinical for further predicting and monitoring the pathological process of bacterial peritonitis.
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Infecciones Bacterianas/sangre , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Peritonitis/sangre , Animales , Biomarcadores/sangre , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Biomarkers of oxidative stress (OS) have been poorly explored in fungal peritonitis (FP). Potassium is a regulator of pro-oxidants and antioxidants. Albumin and vitamin B12 (B12) are vital antioxidant agents in the circulatory system. This study aimed to investigate the antioxidative role of serum potassium, albumin and B12 in FP. METHODS: Serum levels of potassium, albumin and B12 were retrospectively analyzed in 21 patients with a confirmed diagnosis of FP, 105 bacterial peritonitis (BP) patients and 210 patients receiving peritoneal dialysis without peritonitis. RESULTS: Serum levels of potassium, albumin and B12 were lower in FP patients than in BP patients. Serum potassium concentration was statistically related to albumin concentration in peritonitis patients. Univariate and multivariate binary logistic regression analysis suggested that serum level of potassium and albumin were independent risk factors of FP when compared with BP. Lower potassium and B12 levels were independently associated with higher rates of technique failure in peritonitis. CONCLUSION: These findings suggest lower serum potassium, albumin and B12 as potential oxidative stress markers of FP and raise the hypothesis that an increased level of OS could contribute to FP.KEY MESSAGESFP remains a serious complication of peritoneal dialysis (PD), with higher morbidity (1-23.8%) and mortality (2-25%), and oxidative stress plays a role in it.Our study suggested serum potassium, albumin and vitamin B12 as potential oxidative stress markers of fungal peritonitis.
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Micosis/diagnóstico , Peritonitis/diagnóstico , Potasio/sangre , Albúmina Sérica , Vitamina B 12/sangre , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Infecciones Bacterianas/complicaciones , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis/sangre , Micosis/complicaciones , Estrés Oxidativo/fisiología , Peritonitis/sangre , Peritonitis/microbiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Previous in vitro studies have shown that protein arginine N-methyltransferase 4 (PRMT4) is a co-activator for an array of cellular activities, including NF-κB-regulated pro-inflammatory responses. Here we investigated the effect of PRMT4 inhibitor TP-064 treatment on macrophage inflammation in vitro and in vivo. Exposure of RAW 264.7 monocyte/macrophages to TP-064 was associated with a significant decrease in the production of pro-inflammatory cytokines upon a lipopolysaccharide challenge. Similarly, thioglycollate-elicited peritoneal cells isolated from wildtype mice treated with TP-064 showed lowered mRNA expression levels and cytokine production of pro-inflammatory mediators interleukin (IL)-1ß, IL-6, IL-12p40, and tumor necrosis factor-α in response to lipopolysaccharide exposure. However, TP-064-treated mice exhibited an ongoing pro-inflammatory peritonitis after 5 days of thioglycollate exposure, as evident from a shift in the peritoneal macrophage polarization state from an anti-inflammatory LY6ClowCD206hi to a pro-inflammatory LY6ChiCD206low phenotype. In addition, TP-064-treated mice accumulated (activated) neutrophils within the peritoneum as well as in the blood (7-fold higher; P < 0.001) and major organs such as kidney and liver, without apparent tissue toxicity. TP-064 treatment downregulated hepatic mRNA expression levels of the PRMT4 target genes glucose-6-phosphatase catalytic subunit (-50%, P < 0.05) and the cyclin-dependent kinases 2 (-50%, P < 0.05) and 4 (-30%, P < 0.05), suggesting a direct transcriptional effect of PRMT4 also in hepatocytes. In conclusion, we have shown that the PRMT4 inhibitor TP-064 induces peritonitis-associated neutrophilia in vivo and inhibits the pro-inflammatory macrophage lipopolysaccharide response in vitro and ex vivo. Our findings suggest that TP-064 can possibly be applied as therapy in NF-κB-based inflammatory diseases.
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Inhibidores Enzimáticos/uso terapéutico , Macrófagos Peritoneales/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Peritonitis/tratamiento farmacológico , Proteína-Arginina N-Metiltransferasas/antagonistas & inhibidores , Animales , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Humanos , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/inmunología , Activación de Macrófagos/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Neutrófilos/inmunología , Peritonitis/sangre , Peritonitis/inducido químicamente , Peritonitis/inmunología , Proteína-Arginina N-Metiltransferasas/metabolismo , Células RAW 264.7 , Tioglicolatos/administración & dosificación , Tioglicolatos/toxicidadRESUMEN
Introduction: During peritonitis, lipopolysaccharides (LPS) cross the peritoneum and pass through the liver before reaching the central compartment. The aim of the present study was to investigate the role of lipoproteins and phospholipid transfer protein (PLTP) in the early stages of LPS detoxification. Material and Methods: Peritonitis was induced by intra-peritoneal injection of LPS in mice. We analyzed peritoneal fluid, portal and central blood. Lipoprotein fractions were obtained by ultracentrifugation and fast protein liquid chromatography. LPS concentration and activity were measured by liquid chromatography coupled with mass spectrometry and limulus amoebocyte lysate. Wild-type mice were compared to mice knocked out for PLTP. Results: In mice expressing PLTP, LPS was able to bind to HDL in the peritoneal compartment, and this was maintained in plasma from portal and central blood. A hepatic first-pass effect of HDL-bound LPS was observed in wild-type mice. LPS binding to HDL resulted in an early arrival of inactive LPS in the central blood of wild-type mice. Conclusion: PLTP promotes LPS peritoneal clearance and neutralization in a model of peritonitis. This mechanism involves the early binding of LPS to lipoproteins inside the peritoneal cavity, which promotes LPS translocation through the peritoneum and its uptake by the liver.
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Líquido Ascítico/metabolismo , Lipopolisacáridos/sangre , Lipoproteínas HDL/sangre , Peritoneo/metabolismo , Peritonitis/metabolismo , Proteínas de Transferencia de Fosfolípidos/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Lipopolisacáridos/toxicidad , Ratones Endogámicos C57BL , Ratones Noqueados , Peritonitis/sangre , Peritonitis/inducido químicamente , Proteínas de Transferencia de Fosfolípidos/sangre , Proteínas de Transferencia de Fosfolípidos/genética , Unión Proteica , Factores de TiempoRESUMEN
Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.
Asunto(s)
Calcio/sangre , Hormona Paratiroidea/sangre , Diálisis Peritoneal/efectos adversos , Peritonitis/sangre , Peritonitis/etiología , Fósforo/sangre , Biomarcadores/sangre , Enfermedades Óseas/sangre , Calcio de la Dieta/sangre , Humanos , Fallo Renal Crónico/sangre , Estudios Retrospectivos , Factores de Riesgo , TaiwánRESUMEN
BACKGROUND: Serum parathyroid hormone (PTH) levels have been reported to be associated with infectious mortality in peritoneal dialysis (PD) patients. Peritonitis is the most common and fatal infectious complication, resulting in technique failure, hospital admission and mortality. Whether PTH is associated with peritonitis episodes remains unclear. METHODS: We examined the association of PTH levels and peritonitis incidence in a 7-year cohort of 270 incident PD patients who were maintained on dialysis between January 2012 and December 2018 using Cox proportional hazard regression analyses. Patients were categorized into three groups by serum PTH levels as follows: low-PTH group, PTH < 150 pg/mL; middle-PTH group, PTH 150-300 pg/mL; high-PTH group, PTH > 300 pg/mL. RESULTS: During a median follow-up of 29.5 (interquartile range 16-49) months, the incidence rate of peritonitis was 0.10 episodes per patient-year. Gram-positive organisms were the most common causative microorganisms (36.2%), and higher percentage of Gram-negative organisms was noted in patients with low PTH levels. Low PTH levels were associated with older age, higher eGFR, higher hemoglobin, calcium levels and lower phosphate, alkaline phosphatase levels. After multivariate adjustment, lower PTH levels were identified as an independent risk factor for peritonitis episodes [hazard ratio 1.643, 95% confidence interval 1.014-2.663, P = 0.044]. CONCLUSIONS: Low PTH levels are independently associated with peritonitis in incident PD patients.
Asunto(s)
Hormona Paratiroidea/sangre , Diálisis Peritoneal , Peritonitis/sangre , Peritonitis/epidemiología , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
ABSTRACT: We aimed to investigate the hypothesis that serum triglyceride (TG) may be an independent predictor of early-onset peritonitis and prognosis in incident continuous ambulatory peritoneal dialysis (CAPD) patients.In this retrospective, observational study, we screened 291 adults admitted to the PD center of the Wuhan No. 1 hospital from August 1, 2013 to November 31, 2017. All biochemical data were collected at the first 1 to 3 months after the initiation of CAPD. Early-onset peritonitis was defined as peritonitis occurring within 6 months after the initiation of PD. All of PD patients were followed up to July 31, 2018. The primary endpoint was the incidence of early-onset peritonitis while the second endpoints included overall mortality and technical failure.A total of 38 patients occurred early-onset PD peritonitis and the Lasso logistic regression selected TG and age in the final model for early-onset peritonitis. We divided patients into two groups based on the median baseline TG levels: TGâ≥â1.4mmo/L group (nâ=â143) and TGâ<â1.4mmol/L group (nâ=â148). There were 34 (11.7%) patients died and 33 (11.3%) patients transferred to hemodialysis during the follow-up, Moreover, a level of TGâ≥â1.4mmol/L at the initiation of CAPD was associated with a significantly increased probability of technical failure (hazard ratio, HR, 1.30; 95% confidence interval, 95% CI, 1.09 to 2.19, Pâ=â.043) and overall mortality (HR, 2.33; 95% CI, 1.16-4.72, Pâ=â.018).Serum TG levels measured at the initiation of PD therapy is an independent predictor of early-onset peritonitis and prognosis of CAPD patients.
Asunto(s)
Fallo Renal Crónico/terapia , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/sangre , Peritonitis/etiología , Triglicéridos/sangre , Adulto , Factores de Edad , Anciano , Biomarcadores , Índice de Masa Corporal , Femenino , Tasa de Filtración Glomerular , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Peritonitis/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores SocioeconómicosRESUMEN
AIMS & BACKGROUND: The early diagnosis of spontaneous bacterial peritonitis (SBP) has been considered important in the overall patient's survival. Ascitic fluid culture examination performance, in the emergency setting, is time-consuming and not always available, so there is a need for easy to apply, rapid and reliable markers for diagnosis of patients with ascites. The present prospective study aimed to determine the early diagnostic value of serum procalcitonin (PCT) levels in decompensated cirrhotic patients (DCPs) with SBP. METHODS: 47 HCV cirrhotic patients with ascites were enrolled for this prospective study. The severity of cirrhosis was classified based on the Child-Pugh criteria. All patients were subjected to paracentesis and ascitic fluid (AF) culture. Serum PCT levels were measured using enzyme-linked fluorescence analysis (ELFA). RESULTS: The diagnostic value of serum PCT levels and WBC/PLT ratios for detecting infections were serum PCT levels (3.63 ± 3.47 ng/mL) in DCPs with infections which were significantly higher than in DCPs without infections (0.505 ± 0.230 ng/mL); p < 0.05. The cut-off value for serum PCT levels was 0.7 ng/mL for the diagnosis of infections in DCPs, for which the sensitivity and specificity were 93.1% and 73.2%, respectively. The AUC was 0.91 (95% CI: 0.83-0.99). CONCLUSION: Serum procalcitonin seems to provide satisfactory diagnostic biomarkers in SBP.
Asunto(s)
Líquido Ascítico/microbiología , Hepatitis C/complicaciones , Hepatitis C/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/etiología , Polipéptido alfa Relacionado con Calcitonina/sangre , Infecciones Bacterianas/sangre , Biomarcadores , Humanos , Recuento de Leucocitos , Peritonitis/sangre , Peritonitis/microbiología , Estudios Prospectivos , Curva ROC , Índice de Severidad de la EnfermedadRESUMEN
In acute peritonitis, any surgical intervention leads to impaired immune protection with the development of postoperative purulent-septic complications, which increases several times the likelihood of death, especially in people with secondary immunodeficiency as a consequence diabetes mellitus. We aimed to study the dynamics of pro- and anti-inflammatory cytokine content in rat serum under experimental acute generalized peritonitis on the background of diabetes mellitus. Fifty-six white rats were used for the study. The determination of the serum cytokine profile was performed by enzyme-linked immunosorbent assay. When comparing the levels of interleukins between the study groups, a statistically significant increase in the level of proinflammatory cytokines was found in the group of diabetic animals during all experimental periods. In particular, the concentration of interleukin - 1ß increased significantly by 94% on day 1 of observation, by 115% on day 3, and by 121% on day 7 compared to the control group. Similarly, a significant increase in TNF-α levels was observed in animals with diabetes. In this group, the most significant increase in the level of TNF-α was recorded on the seventh day of the experiment, and it increased by 3.4 times. Animals with acute peritonitis on the background of diabetes had a significantly increased concentration of anti-inflammatory cytokines in the serum of all study groups, which confirms their involvement in the pathogenesis of the disease under study.
Asunto(s)
Citocinas/sangre , Diabetes Mellitus/sangre , Peritonitis/sangre , Peritonitis/complicaciones , Animales , Ensayo de Inmunoadsorción Enzimática , Mediadores de Inflamación/sangre , Masculino , Ratas , Factor de Necrosis Tumoral alfa/sangreRESUMEN
INTRODUCTION: Trauma, hemorrhage, and peritonitis have widely varying impacts on endocrine response in the injured patient. We sought to examine cortisol response in established non-human primate models of traumatic hemorrhage and intra-abdominal contamination. METHODS: Cynomologus Macaques were separated into two experimental groups, the polytrauma and hemorrhage model, involving a laparoscopic liver resection with uncontrolled hemorrhage, cecal perforation, and soft tissue excision; and the traumatic hemorrhage model, involving only liver resection and uncontrolled hemorrhage. Cortisol levels were measured pre-operatively, at the time of injury, and at regular intervals until post-operative day 1. RESULTS: Cortisol levels increased 600% from the pre-operative value in the polytrauma and hemorrhage model, with minimal changes (20%) in the hemorrhage only model. CONCLUSION: Cortisol levels increase dramatically in response to polytrauma and intra-abdominal contamination as compared to hemorrhage only. The lack of response in the hemorrhage only group may be due to relative adrenal insufficiency caused by the shock state or lack of enticing stimuli from fecal peritonitis.