Sepsis and identification of reliable biomarkers for postoperative period prognosis.

Sepsis is currently defined as the presence of organ dysfunction occurring as the result of a disturbed host response to a serious infection. Sepsis is one of the most common diseases, which cause mortality and a considerable absorber of healthcare resources. Despite progress in technology and improving knowledge of pathophysiology, the disease mechanism is still poorly understood. At present, diagnosis is based on non-specific physiological criteria and on the late identification of the pathogen. For these reasons, the diagnosis may be uncertain, treatment delayed or an immunomodulatory therapy cannot be established. An early and reliable diagnosis is essential to achieve better outcomes on disease progression. The host response to infection involves hundreds of many mediators of which have been proposed as biomarkers. There is a need for new diagnostic approaches for sepsis, new sepsis biomarkers that can aid in diagnosis, therapeutic decision and monitoring of the response to therapy. The differentiation of sepsis from non-infectious systemic inflammatory response syndrome is difficult, and the search for a highly accurate biomarker of sepsis has become one important objective of the medicine. The goal of our review is to summarize the recent advances on the most commonly studied serum biomarkers, evaluated in clinical and experimental studies, for early diagnosis of sepsis and their informative value in diagnosis, prognosis, or response to therapy. In this context, we have tracked the clinical utility of measuring serum biomarkers, such as procalcitonin, pro- and anti-inflammatory cytokines, C-reactive protein, leptin and their combinations. Currently, has not been identified an ideal biomarker to aid in the diagnosis of sepsis. It is hoped that the discovery of new serum markers, as well as their combinations, will serve for the diagnosis and prognosis of sepsis.

Urinary tract infection with Klebsiella pneumoniae in Patients with Chronic Kidney Disease.

Study Motivation: After assessing electronic databases of medical scientific literature, we have observed that the interrelation between urinary tract infections (UTIs) and chronic kidney disease (CKD) is poorly studied, especially when UTIs are caused by Klebsiella pneumoniae (K. pneumoniae). MATERIALS AND METHODS: K. pneumoniae was isolated in 14 urine samples from patients with CKD addmited in the Nephrology Department of the County Emergency Clinical Hospital Craiova. The isolated strains were statistically analyzed in the correlation with the different clinical and functional parameters (age, gender, CKD stage, comorbidities, biochemical parameters-serum urea, creatinine, uric acid and blood electrolytes). The degree of K. pneumoniae susceptibility to antibiotics from different pharmacodynamic classes was assessed. RESULTS: UTIs with K. pneumoniae in patients with CKD in the investigated period represented 0.51% from the total admissions in the clinic and 32.60% from cases of UTI. Eleven patients with this type of infection (78.56%) were in stage 4 and 5 CKD, and from them 4 also had diabetes mellitus type 2 (28.57%). We observed an increased level for serum creatinine (100%), blood urea (85.71%), and serum uric acid (45.45%). Two patients died after installation of cardiovascular changes in CKD, at advanced ages and in the presence of urinary infection. Multiple drug resistance occurred in 6 strains of K. pneumoniae correlated with the degree of kidney failure, advanced age, male gender, and diabetes mellitus. CONCLUSIONS: UTI with K. pneumoniae in patients with CKD is the second cause of urinary infection which raises problems of unfavorable evolution of CKD and also the recurrence of UTI with multiple drug resistance in CKD, which may lead to pharmacotherapeutical problems.

The role of autoantibodies in health and disease.

Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies, called natural antibodies, are particularly IgM isotype, are considered natural autoantibodies (NAA), displaying a moderate affinity for self-antigens. Although incidence of NAA in healthy individuals is not reported, it is established that autoreactive antibodies and B-cells, as well as autoreactive T-cells, are present in healthy persons. The functional abilities of NAA are not clear but is well accepted that they may participate in a variety of activities, such as maintenance of immune homeostasis, regulation of the immune response, resistance to infections, transport and functional modulation of biologically active molecules. On the other hand, specific adaptive immune responses through high-affinity, class-switched IgG autoantibodies, which bind self-proteins, can cause tissue damage or malfunctions, inducing autoimmune diseases. The new technology that allows for more autoantibody screening may further enhance the clinical utility of autoantibody tests, making it possible to diagnose autoimmune disease in its early stages and to intervene before installing injuries. The aim of this review paper is to succinctly analyze the progress in the physiological role and regulatory significance of natural autoantibodies in health and disease.

TNF-α evaluation in tonsil cancer.

Squamous cell tonsil carcinoma is the most frequent form of oropharyngeal cancer, representing 70-80% of the total of head and neck malignant tumors. Poor clinical symptoms make that 60-80% of patients with squamous cell tonsil carcinoma have a late diagnosis, in the third and fourth stages, when the tumor exceeds the organ limits, invading the pharyngeal wall or the tongue base, being associated with metastases in the laterocervical lymphatic ganglions. The tumor necrosis factor alpha (TNF-α) represents an important inflammation mediator associated to carcinogenesis and even to tumor progression. We evaluated the seric values of TNF-α in a group of patients with tonsil cancer in comparison to a group of patients with chronic tonsillitis, as well as the reaction of mastocytes and macrophages in the two types of tonsil lesions. Seric levels of TNF-α in squamous cell tonsil carcinoma were quite high, varying from 1000 to 2000 pg÷mL, and in four patients, with poorly differentiated tonsil carcinoma in the fourth stage, the TNF-α values varied from 2000 to 4000 pg÷mL. In the patients undergoing radiotherapy, the TNF-α seric levels were within normal limits. In chronic tonsillitis, the TNF-α seric level varied from 10 to 200 pg÷mL. There were not observed any significant differences between the two types of tonsil lesions, regarding the macrophages and mast cells density on the surface unit.

Proatherogenic adipocytokines levels in metabolic syndrome.

INTRODUCTION: Metabolic syndrome was defined by IDF (International Federation for Diabetes, 2007) by abdominal obesity plus at least two of the following: high triglycerides, low HDL-cholesterol, hypertension, high levels of glucose or type II diabetes diagnosed. Obesity is associated with a high cardiovascular risk, abdominal obesity being the most aggressive form, because it secretes cytokines and hormones in comparison to subcutaneous adipose tissue. Adipocytokines secreted by adipose tissue are mediators of atherosclerosis and endothelial damage. MATERIALS AND METHODS: We studied a total of 80 subjects aged between 40 and 60 years with metabolic syndrome, in which the following adipocytokines values were determined: hs-CRP (turbidimetric method), IL-6, TNF-alpha, leptin (ELISA method), in comparison to a control group. RESULTS: The values of these adipocytokines were significantly higher in the studied group compared with the control group and correlated with increased levels of glucose (patients with type II diabetes or increased tolerance test) and with hyper-triglyceridemia. CONCLUSIONS: Patients with metabolic syndrome had increased levels of proatherogenic adipocytokines, particularly leptin, leptin-resistance representing the pathogenic link of obesity. The identification as early as possible of the metabolic syndrome patients allows effective monitoring and correction of cardiovascular risk factors, with the opportunity to reduce morbidity and mortality in young ages. In men, proatherogenic cytokines values presented higher values than in women, which prove the role of abdominal obesity in proatherogenic cytokines production. Although women have a higher percentage of adipose tissue, this is not primarily abdominal adipose tissue.

Matrix metalloproteinases (MMP-3 and MMP-9) implication in the pathogenesis of inflammatory bowel disease (IBD).

Inflammatory bowel disease is a chronic disease, with unknown etiology, characterized by a sustained inflammatory cascade that gives rise to the release of mediators, capable of degrading and modifying bowel wall structure. The present study investigated changes of circulating metalloproteinases (MMP-3, MMP-9) and CRP levels in patients with ulcerative colitis and Crohn's disease, in order to contribute to the elucidation of pathogenesis. We have studied serum samples of 67 patients, of which 46 with ulcerative colitis (mean age 44.8 years) and 21 affected by Crohn's diseases (mean age 39.52 years), who were hospitalized in the Clinic of Gastroenterology of the Emergency County Hospital of Craiova, Romania. For the quantitative determination of MMP-3, MMP-9 and CRP, the ELISA technique was used. Both patients, with Crohn's disease and ulcerative colitis, showed increased production of studied immunomarkers, which were correlated with some clinical stages, indicating their involvement in the disease activity.

Investigation of inflammatory activity in ulcerative colitis.

Inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease are lifelong disorders, characterized by the chronic inflammation of all or part of our digestive tract. Cytokines have an essential role in the pathogenesis of IBDs, because they control the inflammatory response, and the disequilibrium of pro-inflammatory/anti-inflammatory cytokines may lead directly to tissue destruction. Histopathologically, these diseases are characterized by the extent and the distribution of mucosal architectural abnormality, the cellularity of the lamina propria and the present cell types, but these features frequently overlap. We performed a prospective study, which included 46 patients diagnosed with ulcerative colitis (UC) (gender ratio 25 males/21 females, mean age 44.8 years) and 30 subjects, with similar demographic characteristics, which were selected from the patients investigated for other digestive disorders, unaffected by UC. Serological investigations were performed by quantitative determination of IL-17, IL-13, and CRP using ELISA sandwich technique. We have achieved significantly higher concentrations of IL-13, IL-17 and CRP in the serum of patients with UC, compared to the control group. We have found in our study correlations between ulcerative colitis activity and serum levels of interleukins, IL-13 and IL-17. Because IL-17 serum levels were significantly correlated with the disease severity and only cytokine had a significantly statistic correlation with high serum levels of CRP in UC patients, IL-17 can be considered an important progress inflammation marker of this disease.

Immunohistological correlation in different stages of squamous cell carcinoma.

Squamous cell carcinoma is one of the most frequent cutaneous carcinomas, this neoplasic process inducing cellular and tumoral immune response modifications. Our study refers at 60 patients, squamous cell carcinoma diagnosed, at whom we determined IL-2, IL-6 and TNF-alpha, using ELISA technique. The discovered results were different, depending on the differentiation form. The cellular immune response presented important modifications only in poor differentiated form of the disease.

Correlations among the serum levels of some interleukins and the histopathological aspects in chronic viral hepatitis C.

UNLABELLED: PREMISES AND OBJECTIVES: The evolution of the infection with the hepatic virus C depends on the defense of the organism, found under the control of a network of cytokines and chemokines. The mechanisms that are causing both viral persistence as well as hepatic pathology are not entirely elucidated. We have proposed to study the amount in which different categories of cytokines are incriminated in the pathogenesis of the chronic liver disease, as well as the eventual correlations between the serum levels of these cytokines and certain histopathological aspects in the chronic viral hepatitis C. PATIENTS AND METHODS: Thirty-five patients with chronic viral hepatitis C (persistent - nine, active - 15, cirrhosis - 11) have been studied, constituting group P, and 20 healthy subjects constituting the reference group (R). In both groups have been determined the serum concentrations of some proinflammatory interleukins (TNF-alpha, IL-6, IL-8), and antiinflammatory (IL-10) cytokines, through the immunoenzymatic technique ELISA. Results. For the proinflammatory cytokines taken into consideration (TNF-alpha, IL-6, IL-8) increased serum values have been determined to the patients with chronic hepatitis C, the maximal level being observed to the patients active chronic hepatitis and cirrhosis (24/35 patients - 68.57%, 19/35 patients - 54.28% and, namely, 18/35 patients - 51.42%). The serum values of IL-10 are increased in 19/35 patients - 54.28%. The direct relationship among the increased levels of IL-10, the astringency of the inflammation and the hepatic functional insufficiency has been taken into consideration. CONCLUSIONS: The immune cellular answer has a fundamental role in the pathogenesis of the liver disease in the patients with chronic viral hepatitis C. The disequilibrium between the pro- and antiinflammatory cytokines participates to the installation of hepatic lesions of cytolysis and/or to the progression of fibrosis. The serum concentrations of the studied cytokines (TNF-alpha, IL-6, IL-8 and IL-10) are correlated to the histopathological spoilages of the liver.