Hemolytic-uremic syndrome: Etiopathogenesis, diagnostics and basic principles of treatment

© 2015, Serbian Medical Society. All Rights Reserved. Hemolytic uremic syndrome (HUS) is a clinical syndrome that is manifested by thrombocytopenia, hemolytic anemia and acute renal failure. A typical HUS is caused by the action of verotoxin on endothelial cells of small blood vessels of the kidneys and the brain. The disorder of regulation of the alternative pathway of the complement system (mutations of genes for proteins that regulate the activity of the alternative complement system, antibodies to the complement factor H) plays the main role in the pathogenesis of atypical HUS. The disease is clinically manifested by symptoms and signs of damage to the kidneys and brain. The diagnosis of HUS is set on the basis of the reduced number of platelets, microangiopathic hemolytic anemia (negative Coombs test, decreased haptoglobin concentration, increased serum total bilirubin and lactate dehydrogenase, the number of schizonts in peripheral blood smear) and increased creatinine concentration in serum. To distinguish the typical from the atypical HUS it is necessary to perform microbiological examination chairs, measured titer anti-verotoxin antibodies and anti-lipopolysaccharide-antibodies and determine the activity of the enzyme ADAMTS13 (mutations in ADAMTS13, anti-ADAMTS13 antibody) and examine the activity of the alternative pathway of the complement system (C3 component of complement, the complement factor H. I, B, expression of MCP on mononuclear cells from peripheral blood. anti-CFH-antibodies). Patients with typical HUS infection are treated with solutions for infusion, antibiotics that do not increase the release of verotoxin dialysis and supportive therapy. In patients with atypical HUS, a therapeutic plasmapheresis is a first-line process, while in patients where there is resistance or dependence of applied plasmapheresis the blocker of the C5 component of complement (eculizumab) is used

Analysis of clinical, haematological and biochemical parameters in patients with infectious mononucleosis

© 2015, University of Kragujevac, Faculty of Science. All rights reserved. Primary infection with Epstein-Barr virus (EBV) usually occurs in early childhood and often does not present clinical symptoms. More than 90% of adults are infected with this virus. A primary infection that occurs in adolescence or adulthood is usually clinically presented as infectious mononucleosis with a triad of symptoms: fever, lymphadenopathy and pharyngitis. Our retrospective study included 51 patients with a median age of 17 (9-23) years and serologically confirmed infectious mononucleosis. All patients with infectious mononucleosis were treated at the Clinic for Infectious Diseases at the Clinical Center in Kragujevac during 2013. We analysed the clinical, haematological and laboratory parameters of patients. The aspartate-aminotransferase levels were increased in 40 patients, with a mean value of 116.24 (±93.22); the alanine-aminotransferase levels were increased in 44 patients, with a mean value of 189.24 (±196.69). Lymphadenopathy was the most common clinical feature upon admission in 49 patients (96%); 38 patients (74.5%) had splenomegaly, and 20 (39%) had hepatomegaly. Twenty-six patients (51%) had leukocytosis with lymphocytosis, while 15 (75%) of the 20 who had a normal leukocyte count also had lymphocytosis. In the present study, we updated the clinical, haematological and laboratory parameters, which may lead to the establishment of an accurate diagnosis and promote further treatment of the patients

Antitumor effect of the chalcone analogue, (E)-1(4-ethoxy-3-methoxyphenyl)-5-methylhex-1-EN-3-one on hela cell line

© 2019, University of Kragujevac, Faculty of Science. All rights reserved. Chalcones represent precursor compounds for flavonoids biosynthesis in plants. Chalcones, 1,3-diaryl-2-propen1-ones, have unique chemical structure with conjugated double bonds and delocalized π-electron system on both aromatic rings. Various studies have shown that chemical structure of chalcone is responsible for their antitumor effect. In our study, we have examined the antitumor effect of chalcone analogue (E)-1-(4-ethoxy-3-methoxyphenyl)-5methylhex-1-en-3-one (CH) on HeLa cells. The antitumor efficiency of different CH concentrations was compared to the antitumor effects of dehydrozingerone and cisplatin. The viability of the cells was evaluated using MTT assay; type of the cell death was evaluated by Annexin V-FITC/7-AAD staining using FACS analysis; morphology changes of treated cells were visualized and compared to untreated cells using phase contrast microscopy. The result of our research showed that CH have a stronger antitumor compared to the effect both of dehydrozingerone and cisplatin. Our results indicated that chalcone analogue induced cell death via activation of apoptosis more powerfully compared to the apoptosis induced with dehydrozingerone and cisplatin

The analysis of risk factors and clinical-demographic characteristics of patients with clostridium dificille infection as well as the outcome of their treatment

© 2016, University of Kragujevac, Faculty of Science, All rights reserved. Pseudomembranous colitis is a frequent nosocomial infection associated with significant morbidity and mortality. Clostridium difficile infection incidence most frequently increases due to unreasonable antibiotic use and the appearance of new hypervirulent bacterial strains, which leads to prolonged hospitalization and an increase in the total cost of hospital treatment. This is a retrospective design study conducted at Clinical Centre Kragujevac from January to December 2014. The patient data were obtained from the protocol of the Virological Laboratory and from medical documentation. All statistical analyses were performed using the computer program SPSS. The descriptive statistical data are expressed as percentage values. Continuous variables are expressed as the arithmetic mean with the standard deviation. Clostridium difficile infection occurred more frequently with elderly patients (123 patients were over 65 years old). Out of 154 patients on antibiotic treatment, 110 patients were treated with a combination of two or more antibiotics from different pharmacological groups. The most represented antibiotics were from the cephalosporin (71.4%) and quinolone (46.3%) groups. A total of 85.8% of the patients used proton pump inhibitors and H2 blockers. Our results describe the clinical and demographic characteristics of patients with diagnosed Clostridium difficile infection. The most prevalent characteristics (age, antibiotic therapy, PPI and H2 blocker use), which other researchers have also mentioned as risk factors, were present in our study as well

Acute kidney damage: Definition, classification and optimal time of hemodialysis

© 2019, University of Kragujevac, Faculty of Science. All rights reserved. Acute damage to the kidney is a serious complication in patients in intensive care units. The causes of acute kidney damage in these patients may be prerenal, renal and postrenal. Sepsis is the most common cause of the development of acute kidney damage in intensive care units. For the definition and classification of acute kidney damage in clinical practice, the RIFLE, AKIN and KDIGO classifications are used. There is a complex link between acute kidney damage and other organs. Acute kidney damage is induced by complex pathophysiological mechanisms that cause acute damage and functional disorders of the heart (acute heart failure, acute coronary syndrome and cardiac arrhythmias), brain (whole body cramps, ischaemic stroke and coma), lung (acute damage to the lung and acute respiratory distress syndrome) and liver (hypoxic hepatitis and acute hepatic insufficiency). New biomarkers, colour Doppler ultrasound diagnosis and kidney biopsy have significant roles in the diagnosis of acute kidney damage. Prevention of the development of acute kidney damage in intensive care units includes maintaining an adequate haemodynamic status in patients and avoiding nephrotoxic drugs and agents (radiocontrast agents). The complications of acute kidney damage (hyperkalaemia, metabolic acidosis, hypervolaemia and azotaemia) are treated with medications, intravenous solutions, and therapies for renal function replacement. Absolute indications for acute haemodialysis include resistant hyperkalaemia, severe metabolic acidosis, resistant hypervolaemia and complications of high azotaemia. In the absence of an absolute indication, dialysis is indicated for patients in intensive care units at stage 3 of the AKIN/KDIGO classification and in some patients with stage 2. Intermittent haemodialysis is applied for haemodynamically stable patients with severe hyperkalaemia and hypervolaemia. In patients who are haemodynamically unstable and have liver insufficiency or brain damage, continuous modalities of treatment for renal replacement are indicated

Induction of mitochondrial apoptotic pathway by raloxifene and estrogen in human endometrial stromal ThESC cell line

© 2016 Termedia & Banach. Introduction: Endometrial hyperplasia is a condition that occurs as a result of hormonal imbalance between estrogen and progesterone. Morphological disturbance of endometrial cells occurs consequently leading towards endometrial cancer. In therapy of endometrial hyperplasia SERMs are used to supress effects of locally high estrogen level in uterus. There is strong evidence suggesting that estrogen could be involved in cell death - apoptosis. There are no experimental data demstrating the direct apoptotic effect of both raloxifene and estrogen on the ThESC cell line. The aim of our study wa sto investigate both cytotoxic and apototic mechanism of raloxifene and estrogen - induced death in the ThESC cell line. Material and methods: In order to determine their cytotoxic and apoptotic effects, various doses of raloxifene and estrogen were applied to the ThESC cell line for 24 h. After the treatment MTT assay, FACS analysis and immunofluoroscence method were conducted. Results: The results of this study for the first time demonstrated the cytotoxic and apoptotic effects of raloxifene and estrogen on human endometrial stromal cell line suggesting the involvement of the inner, mitochondrial apoptotic pathway. Conclusions: Our results demonstrated apoptotic effects of investigated drugs in the ThESC cell line through increasing the Bax/Bcl-2 ratio and activation of caspase 3

Teucrium polium induces apoptosis in peripheral blood lymphocytes isolated from human chronic lymphocytic leukemia

© 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Background/Aim. Chronic lymhocytic leukemia (CLL) is considered more as a disease of cells accumulation due to the defect in apoptosis rather than deregulated cell's proliferation. The activation of apoptosis is one of the main molecular mechanisms responsible for anti-cancer activities of most of the currently studied potential anti-cancer agents, including natural compounds. Teucrium polium (TP) extracts exhibited strong cytotoxic effects in murine leukemia cell line, RAW 264.7 and human melanoma cell line, C32, but their cytotoxic effects against human leukemia cells were unknown. Methods. The viability of human leukemia cell lines (MOLT 4 and JVM 13), lymphocytes isolated from 28 patients with CLL (CLL cells), and peripheral blood mononuclear cells (PBMCs) isolated from 16 healthy subjects treated with TP leaves methanolic extract, was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of TP treated CLL cells was measured by flow cytometry applying Annexin V/7AAD staining. The expressions of active proapoptotic protein Bax, antiapoptotic protein Bcl-2, cytochrome c and the percentage of cells containing cleaved caspase-3 in treated CLL cells was determined by flow cytometry and immunocytochemistry. Results. The TP methanolic extract decreased the viability of all tested human leukemia cells but it had no effect on the viability of PBMCs isolated from healthy subjects. The cytotoxic effect of TP was caused by its induction of CLL cells' apoptosis. TP disarranged the ratio of the expressions of proapoptotic Bax and antiapoptotic Bcl-2 protein in favor of Bax, consequently inducing apoptosis by cytochrome c mitochondrial release and activation of caspase-3 in treated CLL cells. Conclusion. The TP leaves methanolic induced selective apoptosis in CLL cells and it affected the expressions of key proteins involved in the regulation of programmed cell death