RESUMEN
Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.
Asunto(s)
Herpesvirus Humano 8/genética , MicroARNs/genética , Sarcoma de Kaposi/genética , Sepsis/genética , Receptor Toll-Like 8/genética , Heridas y Lesiones/genética , APACHE , Negro o Afroamericano , Anciano , Estudios de Casos y Controles , Retroalimentación Fisiológica , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Interleucina-6/sangre , Interleucina-6/genética , Interleucina-8/sangre , Interleucina-8/genética , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Leucocitos Mononucleares/virología , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Sarcoma de Kaposi/sangre , Sarcoma de Kaposi/etnología , Sarcoma de Kaposi/mortalidad , Sepsis/sangre , Sepsis/etnología , Sepsis/mortalidad , Transducción de Señal , Análisis de Supervivencia , Receptor Toll-Like 8/sangre , Heridas y Lesiones/sangre , Heridas y Lesiones/etnología , Heridas y Lesiones/mortalidadRESUMEN
MicroRNAs are non-coding RNA fragments, well characterized and well preserved along the evolution of the species and whose essential role is to regulate gene expression. MicroRNAs perform its action on messenger RNA ("target"). They induce degradation or repression of target translation with a significant decrease in the quantity and the activity of proteins. MicroRNAs are involved in normal cell function. Abnormal levels of microRNA were found in several pathological contiditions such as cancer, autoimmune diseases, viral infections, sepsis. Sepsis appears as a result of an improper inflammatory response after systemic bacterial infection. It remains a disease with a high incidence and mortality despite the evolution of diagnostic and treatment techniques. Sepsis patients have similar features to those found in the endotoxin tolerance phenomenon. Endotoxin tolerance is a state of hyporesponsivness to endotoxin challenge induced by a prior exposure. Due to its important role in repression of the pro-inflammatory cytokines translation, microRNA can be considered a new mechanism of endotoxin tolerance and a new mechanism involved in sepsis pathogenesis. In sepsis patients abnormal levels of the following types of microRNA were found: miR-146, miR-155, miR150, miR-132. Further studies are carried out to demonstrate the potential role of microRNA as biomarkers in sepsis.
Asunto(s)
Endotoxinas/inmunología , MicroARNs/inmunología , Sepsis/inmunología , Biomarcadores/sangre , Endotoxemia/inmunología , Regulación de la Expresión Génica , Humanos , Tolerancia Inmunológica/inmunología , Inmunidad Innata , MicroARNs/genética , Pronóstico , Sepsis/genética , Sepsis/microbiologíaRESUMEN
The degree of advancement as well as symptoms of renal osteodystrophy improve significantly in patients after successful kidney transplantation; however bone pathology is still present even after many post-transplant years. The aim of this study was to analyze the bone densitometry in patients during different periods after kidney transplantation and to assess bone metabolism using selected biochemical markers of bone turnover in comparison to healthy controls. Study population consisted of 73 patients of mean age 41.7 +/- 12.6 years (27F, 46M) mean 34 +/- 42 months after kidney transplantation. Mean period of maintenance dialysis prior to surgery was 28.6 +/- 20.3 months. We also analyzed age- and sex-matched control group of 24 subjects. Three-point densitometry was performed with DEXA technique. Serum levels/activity of osteocalcin, C-terminal propeptide of procollagen type I (PCTP), alkaline phosphatase (AP) and its bone-specific isoform (BAP) as well as desoxypiridine (DPD) urine level were analyzed as markers of bone turnover. Serum levels/activity of all mentioned parameters were significantly increased (p < 0.001) and urine DPD--significantly decreased (p < 0.05) in patients as compared to controls. Based on DEXA technique 26% of patients were categorized as having osteoporosis, 32.9%--osteopenia and 41.1% as normal in bone densitometry. Patients with diagnosed osteoporosis spent significantly longer time with functioning graft as compared to those with normal densitometry. In addition, subjects with osteoporosis were characterized by significantly higher serum level of osteocalcin as compared to those with osteopenia and normal DEXA (42.5 +/- 19.9 vs 26.6 +/- 15 ng/ml and 42.5 +/- 19.9 vs 30.2 +/- 104 ng/ml, respectively; p < 0.05). Identical relationship was also observed for serum PTH (128 +/- 42 vs 77.2 +/- 30.4 pg/ml and 128 +/- 42 vs 81.2 +/- 232 pg/ml, respectively; p < 0.001). There was also significant difference in PCTP level in all analyzed groups (203 +/- 85, 171 +/- 69 and 137 +/- 40 ng/ml in subjects with osteoporosis, osteopenia and normal; p < 0.05 for all differences). BAP activity reduction was observed only in the latter group of patients. Results of our study led us to conclude that the prevalence of osteoporosis and osteopenia in three-point densitometry among patients with functioning graft is high. Increased serum levels/activity of osteocalcin, PCTP, AP and BAP with concomitant decrease of urine DPD elimination suggest the predominance of bone formation over the bone resorption process.
Asunto(s)
Biomarcadores/sangre , Biomarcadores/orina , Huesos/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/metabolismo , Trasplante de Riñón , Absorciometría de Fotón , Adulto , Fosfatasa Alcalina/sangre , Aminoácidos/sangre , Aminoácidos/orina , Resorción Ósea , Huesos/diagnóstico por imagen , Proteínas de Unión al Calcio/sangre , Estudios de Casos y Controles , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico por imagen , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteocalcina/sangre , Factores de TiempoRESUMEN
The aim of the study was an analysis of renal transplantation results in the Krakow Transplant Center during 1992-2000. The analysis concerned 94 cadaveric transplant recipients. The study group included 31 females aged 23 to 61 years (mean 40.4 years) and 63 males aged 16 to 60 years (mean 41.8 years). The time of pre-transplant renal replacement therapy ranged from 4 to 120 months (mean 32 months). The mean time of total ischaemia was 22 hours 20 minutes. The majority of the recipients had three identical antigens out of six typed. Most of the recipients were treated with three immunosuppressive drugs including: Cyclosporine A, Azathioprine and steroids. Immediately after kidney transplantation 25.6% of the patients had urine output and did not require dialysis. Acute renal failure (ARF) of the graft was observed in 73.2% recipients. The average number of hemodialysis sessions in patients presenting ARF was 10. Acute rejection was diagnosed in 41.5% of the patients. The most frequent complications were: CMV (cytomegalovirus) infection, UTI (urinary tract infection) and policytemia. In the study group 1-year survival rate of the patients was 97.8% and 1-year graft survival was 93.61%. The 5-year survival rates both in the patients and the grafts were very satisfactory (96.96% and 87.7% respectively).
Asunto(s)
Rechazo de Injerto/epidemiología , Trasplante de Riñón/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Diálisis Renal/estadística & datos numéricos , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Adulto , Infecciones por Citomegalovirus/epidemiología , Supervivencia sin Enfermedad , Femenino , Humanos , Terapia de Inmunosupresión/métodos , Incidencia , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/inmunología , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Tasa de Supervivencia , Resultado del Tratamiento , Infecciones Urinarias/epidemiologíaRESUMEN
Multiple myeloma is the most frequent dysproteinemia leading to nephropathy. The aim of the study was to analyse this complication in patients treated in nephrological departments. The study was performed in 83 patients (45 M, 38 F) aged 47-82 years in whom a diagnosis of multiple myeloma was based on clinical manifestation (weakness, subfebrile states, bone aches, loss of body weight, recurrent infections of urinary and respiratory tracts), increased number of plasmocytes in bone-marrow, presence of monoclonal protein in serum and/or urine and lesions in bone system. In a significant number of the studied patients the disease was revealed while diagnosing proteinuria as well as searching for a reason of elevated erythrocyte sedimentation rate or proteinogram abnormalities. The obtained results indicate that signs of nephropathy in the course of multiple myeloma may be the first visible symptoms of the disease. Proteinuria was observed in 79.5% of the studied patients. Bence-Jones protein was found in 41% of individuals and features of renal failure in different stages of development in 67%. Dialysis therapy was started in 3 patients with acute and 7 patients with chronic renal failure.