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Perinatal asphyxia (PA) is a condition characterized by a gas exchange disorder due to a lack of blood flow or gas exchange, with potential multiorgan dysfunction. Our study aimed to determine the correlation between biochemical markers and echocardiography findings in a group of asphyxiated newborns. The prospective cohort study included 120 neonates (52/120 with PA) treated at a tertial referral pediatric center, from 2012 to 2014. A moderate-strong positive correlation was recorded between the transtricuspid pressure gradient (TRPG) and serum lactate, and between TRPG and NT-proBNP in the PA group (P

Urosepsis is defined as sepsis caused by urinary tract infection (UTI). Urosepsis represents a quarter of all cases of sepsis in adults. Complications of UTIs are the most common risk factor for urosepsis development. These infections, especially pyelonephritis, often occur in patients with structural or functional malformations that interfere with normal urine flow. The problem of a significant increase in UTIs with multiresistant bacteria should be emphasized, especially in patients with recurrent UTI and their frequent treatments. As the urogenital tract is one of the most common sources of infection in sepsis in general, a detailed assessment of the tract should be carried out in all septic patients. Even though urosepsis is associated with a relatively good prognosis and lower mortality than sepsis of another etiology, it occurs rapidly and progresses at a significant speed. Since urosepsis is mainly the result of obstruction of the urinary tract, the development of septic shock can most often be prevented by implementing early deobstruction. Knowledge of the most common causes of urosepsis and the category of high-risk patients will provide clinicians with the tools with which to prevent its occurrence.

Introduction/Objective. Continuing Medical Education (CME) is a crucial element to keep the level of professionalism in the three key fields of medical education: pre-clinical, clinical, and public health. The profile of CME in Serbia has been analyzed for the 2011?2017 period. Methods. Between 2011 and 2017, 11,557 courses of CME have been submitted for accreditation, described by 26 variables. Due to the predominance of nominal data, we employed a principal component analysis (PCA) using the nonlinear iterative partial least squares algorithm (PCA/PLS) to arrange the 16 variables with complete information in such a way that most influential factors could be displayed and ranked. The analysis was done with TIBCO Statistical Software. Results. The Faculty of Medicine of Belgrade takes the top position among the medical faculties in Serbia with 569 courses or 47.9% (n = 1187; 2011?2017), whereas non-educational institutions with 86.2% of all courses (n = 11,514) are the most dominant providers. Clinical topics dominate the thematic spectrum with 59.7%. Between 2012 and 2017, the total number of courses offered diminished by 16.9%. A PCA of 16 potential determinants of CME reveals that the most relevant ones are duration, credit points, price, and number of lecturers. Conclusion. For the last decade, a standstill or even a regression in the development can be observed. Especially the faculties of medicine in Serbia, as well as other major providers, should reconsider the entire structure of their administrative organization and initiate innovative development.

Supplemental Digital Content is available in the text., Background: Cardiovascular complications with myocarditis in multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 infection have been reported, but the optimal therapeutic strategy remains unknown. Methods: A retrospective cohort study included 19 patients with acute left ventricular systolic dysfunction associated with MIS-C, average years of age 13.2 ± 3.8, treated from April 2020 to April 2021. Results: Treatment failure (TF) was observed in 8 patients (in the intravenous immunoglobulin [IVIG] group 7/10; in the corticosteroid [CS] group 1/9). The independent risk factor for TF was IVIG treatment (odds ratio [OR] 18.6, 95% confidence interval [CI] 1.6–222.93, P = 0.02). Patients initially treated with CS became afebrile during in-hospital day 1 (1.5, interquartile range [IQR] 1–2), while IVIG-treated patients became afebrile on in-hospital day 4 (IQR 2–4.25), after CS was added. The C-reactive protein (CRP) significantly declined in CS-treated patients on day 2 (P = 0.01), while in the IVIG group, CRP decreased significantly on the fourth day (P = 0.04). Sodium and albumin levels were higher on third in-hospital day in the CS group than in the IVIG group (P = 0.015, P = 0.03). A significant improvement and normalization of ejection fraction (EF) during the first 3 days was observed only in the CS group (P = 0.005). ICU stays were shorter in the CS group (4, IQR 2–5.5) than in the IVIG group (IVIG group 7, IQR 6–8.5) (P = 0.002). Conclusions: Among children with MIS-C with cardiovascular involvement, treatment with CS was associated with faster normalization of LV EF, fever, laboratory analysis, and shorter ICU than IVIG-treated patients.

Paper description: Chronic exposure to glucose-based peritoneal dialysis (PD) solutions causes peritoneal injury as a result of upregulation of vascular endothelial growth factor (VEGF) with proinflammatory and proangiogenetic activities. Few studies have examined the in vivo effects of VEGF on the peritoneal membrane in humans. Observed significant inverse correlations between drained dialysate VEGF concentrations, residual diuresis and residual renal function at chronic PD onset point to the importance of preserved residual renal function in achieving VEGF clearance. The predictive value of drained dialysate VEGF in identifying patients with preserved transport characteristics of peritoneal membrane and efficacious long term PD maintenance is emphasized. Abstract: Vascular endothelial growth factor (VEGF), a powerful angiogenetic agent crucial for microvascular hyperpermeability and neoangiogenesis in the peritoneum, is associated with increased solute transport rates in chronic peritoneal dialysis (PD) patients. We investigated the correlation between serum and drained dialysate (dd) concentrations of VEGF and the transport characteristics of peritoneal membrane and dialysis quality in 20 patients with end-stage renal failure at the beginning and after six months of PD. The serum VEGF (sVEGF) concentration rose significantly (149.33±116.71 pg/mL vs 239.36±102.23 pg/mL; p=0.012) and ddVEGF concentration increased slightly (38.44±50.47 pg/mL vs 43.55±51.10 pg/mL) during the first 6 months of PD. At the beginning of chronic PD, ddVEGF concentrations correlated inversely with the peritoneal equilibrium test (PET) glucose (R=-0.565; p=0.009) and creatinine (R=-0.506; p=0.023) and residual renal function (RRF) (R=-0.691; p=0.001); sVEGF concentrations inversely correlated with PET creatinine (R=-0.457; p=0.043) and residual diuresis (RD) (R=-0.691; p=0.001). After 6 months of treatment, ddVEGF concentrations correlated directly with PET creatinine (R=0.450; p=0.047), and inversely with RRF (R=-0.552; p=0.012) and residual renal weekly Kt/V (R=-0.488; p=0.029). The sVEGF concentration inversely correlated with RD (R=-0.589; p=0.006). High ddVEGF at the beginning of PD is predictive of adverse alterations of the peritoneal membrane, i.e. increased transport rate of glucose and creatinine. ddVEGF values may help to identify patients who will preserve adequate transport characteristics of the peritoneal membrane and maintain successful long-term PD. https://doi.org/10.2298/ABS181120061J Received: November 20, 2018; Revised: December 19, 2018; Accepted: December 22 2018; Published online: December 27, 2018 How to cite this article: Jovanovic NŽ, Žunic SS, Trbojevic-Stankovic JB, Lausevic ŽD, Nesic DM, Stojimirovic BB. The relationship between vascular endothelial growth factor (VRGF) in the serum and drained dialysate with the quality of peritoneal dialysis and peritoneal membrane transport rates. Arch Biol Sci. 2018;71(1):187-94.

Paper description: Tumor markers are significant for early detection of (pre)malignant lesions, local recurrence and distant metastasis, prevention of secondary tumors, appropriate therapeutic protocol choice, and as a prognostic factor for disease progression. In this prospective case, immunohistochemical expression of the tumor markers PCNA, HER-2 and CD-31 in patients with oral squamous cell carcinoma undergoing the same surgical treatment during a ten years period was determined. Increased expression of PCNA during advanced stage of the disease may be a useful biomarker in determining further disease progression. PCNA can be useful in routine clinical practice. Abstract: Several studies have investigated the expression of tumor markers, including p53, HER-2, PCNA, EGFR, VEGFR CD-31 and Bcl-2 in patients with oral squamous carcinoma (OSC). This study aimed to determine the expression of proliferating cell nuclear antigen (PCNA), endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31) and human epidermal growth factor receptor-2 (HER-2) according to OSC stage. The prospective study included 62 patients diagnosed with OSC stages II and III. Surgical specimens were obtained from tumor and peritumoral tissues. We determined the pathohistological degree of tumor differentiation and the immunohistochemical expression of PCNA, CD-31 and HER-2 for each specimen. Immunohistochemical analysis of the expression of PCNA in tumor cells demonstrated poor staining of immunoreactive tumor cells in 23 patients (10 in stage II, 7 in stage IIIa and 6 in stage IIIb). Moderately expressed PCNA-immunoreactivity in the tumor cells in 17 patients (7 in stage II, 6 in stage IIIa and 4 in stage III), and extremely strong PCNA-immunoreactive staining in tumor cells of 10 patients with IIIb stage, was observed. These results suggest that PCNA expression combined with pathohistological findings could possess a prognostic value in determining the survival rates for patients with oral squamous cell carcinoma. https://doi.org/10.2298/ABS190705053L Received: July 5, 2019; Revised: August 4, 2019; Accepted: August 6, 2019; Published online: August 30, 2019 How to cite this article: Loncarevic SA, Brajkovic DO, Gardasevic MF, Loncarevic OLj, Lađevic NG, Nesic DM, Stamenkovic DM, Likic-Lađevic IS, Lađevic NN, Rancic NK. Expression of PCNA, CD-31 and HER-2 in Serbian patients with oral squamous cell carcinoma. Arch Biol Sci. 2019;71(4):703-10.

BACKGROUND: Acute myocarditis (AM) is defined as inflammation of the myocardium. The aim of our study is a comparative analysis of the differences between AM related and unrelated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The retrospective study included children with AM treated from January 2018 to November 2020. RESULTS: The study included 24 patients; 7 of 24 had AM related to SARS-CoV-2 and they were older than 7. They were more likely to have abdominal pain (P = 0.014), headache (P = 0.003), cutaneous rash (P = 0.003), and conjunctivitis (P = 0.003), while fulminant myocarditis was commonly registered in AM unrelated to SARS-CoV-2 (P = 0.04). A multisystem inflammatory syndrome in children associated with COVID-19 was diagnosed in six adolescents. Patients with AM related SARS-CoV-2 had lower serum cardiac troponin I (cTnI) (P = 0.012), and platelets (P < 0.001), but had a higher C-reactive protein (CRP) value (P = 0.04), and N-terminal-pro hormone BNP in comparison to patients with AM unrelated to SARS-CoV-2. The patients with AM related to SARS-CoV-2 had significant reduction of CRP (P = 0.007). Inotropic drug support was used for shorter durations in patients with AM related to SARS-CoV-2, than in others (P = 0.02). Children with AM related to SARS-CoV-2 had significant improvement of left ventricle systolic function on the third day in hospital (P = 0.001). Patients with AM unrelated to SARS-CoV-2 AM had more frequent adverse outcomes (P = 0.04; three died and four dilated cardiomyopathy). CONCLUSIONS: In contrast to patients with AM unrelated to SARS-CoV-2, patients with AM related to SARS-CoV-2 had a higher CRP value, polymorphic clinical presentation, shorter durations of inotropic drugs use as well as prompt recovery of left ventricle systolic function.

The novel coronavirus disease (COVID-19) may induce multisystem inflammatory syndrome in children, which may be associated with Kawasaki-like disease, and cardiac injury. In this study, we presented three male adolescents with multisystem inflammatory syndrome and myocardial injury admitted to the hospital during the peak of COVID-19 pandemic. All of the three patients had a history of fever, gastrointestinal symptoms, polymorph rash, non-exudative conjunctivitis, and signs of acute myocarditis. One of them had renal failure. Previously, they did not have an acute infection. Upon admission, they were hypotensive and tachycardic. A nasopharyngeal swab for SARS-CoV-2 on reverse transcription-polymerase chain reaction (PCR) assay was negative, but neutralizing viral antibodies were positive. In combination with blood tests, ECG, echocardiography and computerized tomography (CT), a multisystem inflammatory syndrome associated with acute myocarditis with mild to moderate systolic dysfunction and dilated coronary arteries were diagnosed. Two of three patients had shock syndrome and required inotropic support. All patients were treated with intravenous immunoglobulins. The second patient had a fever up to 102.2°F (39°C) three days after intravenous immunoglobulins. Further, he was treated according to protocols for refractory Kawasaki disease, with an intravenous methylprednisolone pulse therapy and aspirin. After a few hours, he became afebrile and the clinical signs disappeared. The favorable short-term outcome may reflect the early recognition and adequate therapy; however, the long-term outcomes are currently unknown.

Objective The predisposing factors for pericarditis recurrence in the pediatric population have not yet been established. This study aimed to define the risk factors for the unfavorable prognosis of pediatric acute pericarditis. Methods This was a retrospective study that included all patients with acute pericarditis treated from 2011 to 2019 at a tertiary referent pediatric center. Results The study included 72 children. Recurrence was observed in 22.2% patients. Independent risk factors for recurrence were: erythrocyte sedimentation rate ≥ 50 mm/h (p = 0.003, OR 186.3), absence of myocarditis (p = 0.05, OR 15.2), C-reactive protein ≥ 125 mg/L (p = 0.04, OR 1.5), and non-idiopathic etiology pericarditis (p = 0.003, OR 1.3). Corticosteroid treatment in acute pericarditis was associated with a higher recurrence rate than treatment with non-steroid anti-inflammatory therapy (p = 0.04). Furthermore, patients treated with colchicine in the primary recurrence had lower recurrence rate and median number of repeated infections than those treated without colchicine (p = 0.04; p = 0.007, respectively). Conclusion Independent risk factors for recurrence are absence of myocarditis, non-idiopathic etiology pericarditis, C-reactive protein ≥ 125 mg/L, and erythrocyte sedimentation rate ≥ 50 mm/h. Acute pericarditis should be treated with non-steroid anti-inflammatory therapy. A combination of colchicine and non-steroid anti-inflammatory drugs could be recommended as the treatment of choice in recurrent pericarditis.

The aim of this study was to evaluate longitudinal changes in drained dialysate cancer antigen 125 (dCA-125) levels and to assess relationships between dCA-125 and dialysis quality, peritoneal membrane transport rates, dialysate glucose load, peritonitis and use of erythropoiesis stimulating agents (ESA), angiotensin-converting-enzyme inhibitors (ACEi) and statins in patients with end-stage renal failure during the first 6 months of peritoneal dialysis (PD) treatment. This prospective study included 20 patients (11 males and 9 females; mean age 62.90±12.69 years) who were followed-up during the first 6 months of PD using conventional low pH glucose-based dialysis fluids. The concentration of dCA-125 was measured in all patients, and the peritoneal equilibration test (PET), peritoneal dialysis treatment adequacy (Kt/V), normalized protein catabolic rate (nPCR), and total, peritoneal and residual clearances of urea and creatinine were calculated. Information on peritonitis occurrence, the use of ESA, ACEi and statins were collected. Data were analyzed by the Mann-Whitney test, Wilcoxon matched pairs test and Spearman’s rank correlation. The concentration of dCA-125 significantly decreased during the follow-up (p=0.016). After 6 months of PD treatment, the concentration of dCA-125 decreased significantly (p=0.016) in all patients. The decrease was present in all patients, but was statistically significant in patients on ACEi therapy (p=0.006) and in patients not using statins (p=0.005) or ESA (p=0.012). No correlation was found between dCA-125 and glucose load, but a statistically significant negative correlation between dCA-125 and the PET for creatinine was observed (p=0.013). These findings challenge the role of dCA-125 in predicting mesothelial cell integrity in PD patients. https://doi.org/10.2298/ABS170324021J Received: March 24, 2017; Revised: May 7, 2017; Accepted: May 9, 2017; Published onlione: June 12, 2017 How to cite this article: Jovanovic NŽ, Trbojevic-Stankovic JB, Nesic DM, Obrenovic RŽ, Boricic NI, Stojimirovic BB. Cancer antigen 125 concentrations in patients on chronic peritoneal dialysis: Relationship with dialysis quality and membrane transport properties. Arch Biol Sci. 2018;70(1):13-20.

Both pregnancy, as physiological, and polycystic ovary syndrome (PCOS), as a pathological condition, carry the risk for developing glucose metabolism abnormalities. In this retrospective cross-sectional study, we hypothesized that pregnancy as a physiological condition carries a higher likelihood for abnormal oral glucose tolerance test (OGTT) results than PCOS as a pathological condition. We have compared the prevalence and likelihood ratios for abnormal OGTT results between non-pregnant women with PCOS (Group A) and pregnant women at 24 to 28 weeks of gestation (Group B). Participants of both study groups underwent glucose tolerance testing with 75 g glucose OGTT. During the study period, 7411 women were tested, 3932 women encompassed Group A, and 3479 women comprised Group B. The numbers of yearly tested pregnant women and the corresponding proportion of tested women among all study participants have decreased during the study period, from 766 to 131 and 89.1% to 20.5%, respectively. Group A had a significantly lower prevalence (4.4%) of pathological OGTT results compared to Group B (8.1%). This has resulted in a 45.427 likelihood ratio (P

Internet addiction is a novel and relatively uninvestigated form of dependence that is fairly common in adolescent population. Previous research has indicated that it may be associated with other mental health problems, such as dysthymic mood and narcissistic behavior. In our study, we tested the existence and strength of relationship between Internet addiction, self-esteem and narcissism in a student population. On a sample of 244 students, we also investigated social networking activities, such as number of self-portrait photographs ("selfies"), and their potential connection with self-esteem and narcissism. Each participant completed a questionnaire consisting of Young Internet Addiction Test, Rosenberg Self-Esteem scale, and Narcissistic Personality Inventory. There was a statistically significant negative correlation between internet addiction score and self-esteem. Internet addiction increased as self-esteem decreased and vice versa. On the other hand, there was a positive correlation between internet addiction and narcissism. NPI score and number of self-portrait photographs (selfies) on Facebook were also in a positive relationship. Conversely, NPI score increased as the self-esteem decreased. The results of the study are in accordance with our previous findings on Internet use and mental health, confirming that Internet addiction is a potentially a serious public health problem.

Nutritional support of surgical patients is a necessary part of the treatment. It alone cannot cure the disease but it significantly affects the recovery of patients and supports surgical interventions. Patients in malnutrition have shown to have significantly more postoperative infectious and non-infectious complications. This significantly prolongs treatment time and increases costs. However, there is one fact that cannot be expressed in money, which is the patient's impression of the surgical intervention. Adequate preoperative patient support, based on the intake of liquid nutritive solutions, reduces preoperative stress and deflects the metabolic response. Now, it is recommended for adults and children older than one year to drink clear liquid up to 2 hours before induction in anesthesia. Appropriate enteral nutrition has a significant place in the postoperative recovery of patients. Enteral nutrition is reducing complications, mainly infectious complications because the function of the digestive system as one large immune system is preserved. Perioperative enteral nutrition is a necessary part of the modern treatment of surgical patients. In addition to the significant effect on the occurrence of postoperative complications, it is also important that this type of diet improves the psychological status of patients.

In this study we investigated the relationship between the calcium channel blockers (CCBs), amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem, and their calculated molecular descriptors: polar surface area (PSA), molecular weight (Mw), volume value (Vol), aqueous solubility data (logS), lipophilicity (logP), acidity (pKa values) and plasma protein binding (PPB) data, obtained from relevant literature. The relationships between the computed molecular properties of selected CCBs and their PPB data were investigated by simple linear regression analysis that revealed very low correlations (R2

The plasma protein binding (PPB) data of twelve antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, chlorpromazine, flupentixol, fluphenazine, haloperidol, zuclopenthixol) were estimated using computed molecular descriptors, which included the electronic descriptor – polar surface area (PSA), the constitutional parameter – molecular weight (Mw), the geometric descriptor – volume value (Vol), the lipophilicity descriptor (log P ) and aqueous solubility data (log S ), and the acidity descriptor (pK a ). The relationships between computed molecular properties of the selected antipsychotics and their PPB data were investigated by simple linear regression analysis. Low correlations were obtained between the PPB data of the antipsychotics and PSA, Mw, Vol, pKa, log S ( R

Target dialysis dose to ensure the best patient outcome is still a matter of debate. Traditional models have a number of limitations and do not comprehensively reflect all factors involved. In this study we present a new complex model of dialysis adequacy, the hemodialysis adequacy score (HAS), and evaluate its prognostic value, as well as its relationship with the malnutrition-inflammation score (MIS). The components of HAS included paradigms of the 6 major factors known to influence the outcome of hemodialysis (HD) patients: the modified Karnofsky index (KI), the Charlson comorbidity index (CCI), Kt/V and URR measures of dialysis dose, body mass index (BMI) and serum albumin level, serum levels of hemoglobin and ferritin, intact parathyroid hormone (iPTH) and calcium-phosphorus solubility product. The score was evaluated in a 24-month prospective study on 147 HD patients. Odds ratio analysis showed that hospitalized patients had twice the chance to have HAS >13 compared to those who were not hospitalized during the study period (OR=2.152, CI 95% (1.0024-4.619). Mortality rate was significantly higher in patients with a HAS >13 at the 12-month follow-up (χ2=16.416, p 13 had significantly higher probability of death (log-rank Cox-Mantel=17.920, df=1, p

Background and Objectives: Recurrence of pericarditis (ROP) is an important complication of the acute pericarditis. The aim of this study was to analyse the influence of aetiology, clinical findings and treatment on the outcome of acute pericarditis. Methods: Data were retrospectively collected from medical records of patients treated from 2011 to 2019 at a tertiary referent heart paediatric center. Results: Our investigation included 56 children with idiopathic and viral pericarditis. Relapse was registered in 8/56 patients, 2/29 (7.41%) treated with nonsteroidal anti-inflammatory drugs (NSAID) and 6/27 (28.57%) treated with corticosteroids (CS) and NSAID. Independent risk factors for ROP were viral pericarditis (p = 0.01, OR 31.46), lack of myocardial affection (p = 0.03, OR 29.15), CS use (p = 0.02, OR 29.02) and ESR &ge, 50 mm/h (p = 0.03, OR 25.23). In 4/8 patients the first recurrence was treated with NSAID and colchicine, while treatment of 4/8 patients included CS. Children with ROP treated with CS had higher median number of recurrence (5, IQR: 2&ndash, 15) than those treated with colchicine (0, IQR: 0&ndash, 0.75). Conclusions: Independent risk factors for recurrence are CS treatment, viral aetiology, pericarditis only and ESR &ge, 50 mm/h. Acute pericarditis should be treated with NSAID. Colchicine and NSAID might be recommended in children with the first ROP.

Objectives Physical activity level decreases during young adulthood. As social media are nowadays widely used and are included into many people's daily routines, the interventions on these websites have the possibilities to be integrated into those routines without becoming a burden. The aim of this study was to assess physical activity level among first- and fifth-year medical students and social media intervention with the aim to improve physical activity among them. Study design Prospective longitudinal study was conducted during October of 2016 at the Faculty of Medicine, University of Belgrade, Serbia. The study included 375 first- and fifth-year students. Methods At the baseline, students filled in the questionnaire and were asked to join a Facebook discussion group. The intervention consisted of motivation for physical activity through motivational pictures, texts, and discussions. The second assessment was carried out after one month. Based on the reported physical activity level, students were divided into groups: sufficient (>600 metabolic equivalent [MET]-minutes/week) and insufficient physical activity (≤600 MET-minutes/week). Results Total of 85.4% of students were sufficiently active at the baseline, whereas 90.4% were sufficiently active after one month. Multivariate logistic regression analysis showed that students who were part of the Facebook group (odds ratio [OR]: 3.51, 95% confidence interval [CI]: 1.46–8.43) and students who had sufficient physical activity at the baseline (OR: 5.44, 95% CI: 2.44–12.13) had a higher likelihood to be sufficiently active after one month. Conclusion Social media are shown to be valuable in health-promoting interventions and can be used for interventions targeting lifestyle change among young adults.

Erythropoietin is a hormone that promotes the formation of red blood cells by the bone marrow. In adults it is mainly produced by the kidneys as a response to hypoxia. Besides its main role, it also acts as antiapoptotic, anti-inflammatory and cytoprotective agent. Furthermore, it is produced in many non-hematopoietic tissues where it acts locally, stimulating angiogenesis. Erythropoietin binds cytokine receptors on target cells, such as erythrocyte precursor cells, neurons, glial and endothelial cells, cardiomyocytes, myocytes etc. The discovery of synthetic erythropoietin forms, in the late eighties of the last century, has significantly improved treatment outcome of patients with anaemia related to chronic diseases, especially chronic renal failure. Renal anaemia is multifactorial, but predominantly a consequence of erythropoietin deficiency. Today, three generations of erythropoiesis stimulating agents are available, differing in glycosylation pattern, molecular size, half-life and modes of administration and dosage. In anaemic patients this therapy significantly improves their quality of life, but may also have serious, potentially dangerous adverse effects. Synthesis of recombinant human erythropoietin, on the other hand, has improved possibilities for manipulations in sport, in the field of blood doping. Erythropoietin administration in athletes increases their maximum oxygen consumption capacity, improves endurance and performance, especially in aerobic exercise. This seriously undermines the spirit of sport, and also endangers athletes' health. Different anti-doping tests have been developed and used, still with limited success. At the same time, new illicit ways of malpractice are developing, such as variuos models of gene doping. Therefore, providing new models of anti-doping tests and strategies, together with better health control of athletes, still remains a considerable challenge.

The article's abstract is no available.

Obstructive sleep apnea (OSA) can lead to severe health consequences. Drivers of motor vehicles with untreated or undiagnosed OSA have a greater risk of traffic accidents. Use of self-reported questionnaires is the first step in OSA diagnosis. The main aim of this study was to perform the translation and validation of Berlin Questionnaire in a sample of commercial drivers. After formal translation, validation was performed on a sample of commercial drivers and included evaluation of internal consistency, test–retest reliability, construct and criterion validity. Full-night attended polysomnography or cardiorespiratory polygraphy was used for OSA diagnosis. One hundred male participants, 24–62 years old, were included. Berlin Questionnaire classified 35 % subjects as potential OSA patients. Polysomnography confirmed OSA in 58 % of the subjects. Berlin Questionnaire showed good internal consistency (Cronbach’s alpha 0.82—first category, 0.73–0.95—second category). Test–retest reliability (Cohen’s kappa 0.78) was adequate. Berlin score was significantly correlated with OSA category and apnea–hypopnea index (AHI). Sensitivity of Berlin Questionnaire was from 50.9 (AHI ≥ 5) to 75 % (AHI ≥ 30), while specificity ranged from 86 to 70.5 %. Berlin Questionnaire (Serbian version) showed good measurement properties, creating basis for further research of its usefulness as OSA screening tool in populations of interest.

Transforming-growth factor β1 (TGF-β1) is a powerful cytokine involved in physiological processes of growth, differentiation, gene expression, embryogenesis, tissue remodelling, wound healing as well as tumorigenesis, immunosuppression and fibrosis, like peritoneal membrane fibrosis on long-term peritoneal dialysis (PD) treatment. The aims of this study were to determine TGF-β1 levels in serum (s) and drained dialysate (dd), to assess their relations to sex, age, diabetes, dialysis modality, peritonitis and use of erythropoiesis stimulating agents (ESAs), inhibitors of angiotensin-converting enzyme (ACEi) and/or statins in 20 patients, 11 men and 9 women, mean age 62.90 ± 12.69 years, free of peritonitis during the first 6 months of PD treatment. There was no statistically significant difference in TGF-β1 concentrations in serum and drained dialysate at the beginning and after first 6 months of chronic PD, in patients of different sex, age and diabetic patients versus non-diabetic. The significant positive correlations between sTGF-β1 levels and glycemia at the beginning and cholesterolemia after 6 months of PD treatment suggest higher TGF-β1 concentrations in patients with unfavorable metabolic profile. Expression of TGF-β1 in effluent dialysate was significantly lower in patients on chronic PD using ACEi therapy, suggesting ACEi to have a protective effect on peritoneal membrane. Patients on ESA had slightly lower sTGF-β1 concentrations after the first 6 months of PD treatment.

Calcium channel blockers (CCBs) are among the most widely used drugs in cardiovascular medicine. In this study, nine CCBs (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem) were investigated to assess the relationship between their molecular properties and elimination data obtained from literature. The descriptors of the molecular properties of CCBs were calculated using three software packages. The relationship between computed molecular properties and elimination data collected from relevant literature, initially investigated with simple linear regression analysis, showed poor correlation (R2

Angiotensin II receptor antagonists (ARBs) modulate the function of the renin-angiotensin-aldosterone system and are commonly prescribed antihypertensive drugs, especially in patients with renal failure. In this study, the relationship between several molecular properties of seven ARBs (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan) and their fecal elimination data obtained from the literature were investigated. The ARB molecular descriptors were calculated using three software packages. Simple linear regression analysis showed the best 2 correlation between fecal elimination data and lipophilicity descriptor, ClogP values (R2 = 0.725). Multiple linear regression was applied to examine the correlation of ARBs’ fecal elimination data with their lipophilicity and one additional, calculated descriptor. The best correlation (R2 = 0.909 with an acceptable probability value, P

Introduction. Chronic peritoneal dialysis (PD) up-regulates vascular endothelial growth factor (VEGF) synthesis and VEGF is found in drained dialysate (dd). Objective. Aims of this prospective study were to evaluate serum (s) and ddVEGF concentration during the first six months of PD, relationships between these concentrations and demographic and biochemical parameters, presence of diabetes, peritonitis, and the use of medications. Methods. The study included 20 patients, with the mean age of 62.9?12.69, 11 of whom were affected by diabetes mellitus. Fasting venous blood samples were taken at the beginning and after six months of PD, in tri-potassium ethylenediaminetetraacetic acid (K3EDTA) vacutainer. Results. After six months of PD, sVEGF concentrations increased significantly, without significant change in ddVEGF. Concentrations of sVEGF at the beginning of chronic PD treatment directly significantly correlated with serum fibrinogen, and after six months with fibrinogen and glycemia. In patients receiving erythropoiesis-stimulating agent (ESA), levels of sVEGF and ddVEGF were lower at baseline, while after six months of PD ddVEGF increased. In patients not receiving ESA, sVEGF increased more prominently, while ddVEGF decreased. The changes were not statistically significant. Patients receiving angiotensinconverting- enzyme inhibitor (ACEi) had sVEGF and ddVEGF levels insignificantly lower than those not using ACEi, however sVEGF significantly increased during six months of PD. After six months of PD, ddVEGF was significantly higher compared to those not using ACEi. Treatment with statins did not significantly influence levels of sVEGF and ddVEGF during the follow-up. Concentrations of sVEGF were continually lower than those of ddVEGF and increased more, while concentrations of ddVEGF were higher in patients using statins. Conclusion. Serum and drained dialysate concentrations of VEGF in PD patients were connected with poorer metabolic profile, while the role of inflammation and treatment agents should be studied further.

Ghrelin is an endogenous peptide potentially useful in therapy of anorexia and other age-related metabolic disturbances. We evaluated the influence of age on the orexigenic and lipid metabolism-altering effects of ghrelin. Peripubertal, young, adult and middle-aged rats (1, 2, 7 and 12 months old, respectively) were treated with 5 daily intracerebroventricular injections of ghrelin (0.15 nmol) or saline (control). The food intake was measured daily before treatment, while white adipose tissue and serum/plasma samples for detection of lipid metabolites/hormones were collected at the end of the experiment. The values of cumulative food intake and body weight gain declined, while the white adipose tissue deposits and blood concentrations of triglycerides, cholesterol and free fatty acids all increased with age. Ghrelin significantly increased all parameters, but the stimulatory effects on body weight gain and food intake were more pronounced in peripubertal/young rats, while the increase in white adipose mass, triglyceride and low-density lipoprotein cholesterol levels was more noticeable in adult/middle-aged animals. The decrease in sensitivity to ghrelin-mediated stimulation of food intake in older animals could not be explained by alterations in ghrelin's ability to reduce anorexigenic hormones insulin and leptin. However, the higher responsiveness of aged rats to ghrelin-mediated increase in lipid metabolites was accompanied by an increase in adrenocorticotropic hormone and corticosterone levels. These results indicate that aging, while reducing sensitivity to ghrelin-mediated increase in body weight gain and food intake, might enhance the responsiveness to the stimulatory effects of ghrelin on lipid metabolites and hypothalamic-pituitary-adrenal axis activity.

We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1 beta, IFN-gamma) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1 beta, IL-6, IFN-gamma, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-beta remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 mu g/day) for five consecutive days significantly reduced TNF, IL-1 beta and IFN-gamma levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of 1FN-gamma, IL-17,1L-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways. (C) 2011 Elsevier Inc. All rights reserved.

Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 microl phosphate buffered saline with or without 1 microg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p

a b s t r a c t Changes in feeding regime represent serious stress, while ghrelin is considered a key player in energy balance. We investigated the effects of intracerebroventricular (ICV) ghrelin application on pituitary adrenocorticotropic (ACTH) cells in rats fed diets differing in energy content. Before the ICV treatment, male Wistar rats were subjected to three different feeding regimes for 4 weeks: normal-fed (NF), food- restricted (FR) or high-fed (HF) (n = 3 × 14). At the age of 8 weeks, rats from each group were divided into two subgroups and given ICV, either ghrelin (G; 1 g ghrelin/5 l PBS, n = 7) or solvent alone (5 l PBS, n = 7) every 24 h for 5 days. The immunohistochemical appearance and quantitative morphology of pituitary ACTH cells were evaluated, as well as peripheral ACTH and corticosterone levels. Central ghrelin administration increased (p < 0.05) ACTH cell volumes in GNF, GFR and GHF rats by 8.1%, 11.8% and 9.1%, respectively, compared to the controls, while significant increases in ACTH cell volume density were observed in GNF and GHF rats. Circulating ACTH and corticosterone levels were elevated (p < 0.05) in GNF and GFR rats by 72.8% and 80.8%, respectively, when compared to the corresponding controls. Thus, central ghrelin administration stimulated the pituitary-adrenal axis under preserved and negative energy balance states.

Nutritional status is the condition of the body as a result of the food intake, absorption and the ability of body to maintain normal metabolic homeostasis. Creatinine is determined by the muscular mass, because it is non-enzymatically derived from creatinine, which is structural component of muscles. Previous studies showed that serum creatinine concentration correlate with body mass index (BMI) in both general and athletic population and proposed that the specific reference ranges should be used in athletes. In the similar manner, aminotransferases are released by activated muscles and could increase after physical exercise. Strong correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with BMI was found in general population, but the data for athletes are still lacking. In addition, the percentage of Body Fat (%BF) has been shown to be more reliable indicator of nutritional status in athletes. The aim of this research was to examine the relationship of anthropometric parameters, BMI and the% BF, with the serum concentration of AST and ALT in male and female athletes (basketball players), and to assess if there are gender specific differences in the level of aminotransferases. The 84 male (22 ± 2 years) and 72 female basketball players (20 ± 2 years) were examined. All subjects had been practiced sports actively for minimum 5 years, at least 15 hours per week. Measured anthropometrical parameters and liver metabolic parameters were: body height (BH), body mass (BM), BMI,%BF (assessed by bioimpedance) and serum concentrations of AST and ALT after at least 12h of fasting and 24h without high intensity physical activity. The BMI was significantly higher (p Our study has showed that BMI and%BF do not correlate with AST and ASL in male athletes, while they strongly correlate in female athletes, therewith%BF correlate better with AST and ALT. As the correlation of BMI and%BF with ALT and AST was linear, future investigation are needed to explain the cause of the close relationship between%BF, AST and ALT obtained in the group of female athletes. References Banfi G, Colombini A, Lombardi G, Lubkowska A. Metabolic markers in sports medicine. Adv Clin Chem 2012;56:1–54. Banfi G, Morelli P. Relation between body mass index and serum aminotransferases concentrations in professional athletes. J Sports Med Phys Fitness 2008;48(2):197–200. Bedogni G, Miglioli L, Masutti F, Castiglione A, Tiribelli C, Bellentani S. Accuracy of body mass index in detecting an elevated alanine aminotransferase level in adolescents. Annals of human biology 2004;31(5):570–77.

Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, 11060 Belgrade, SerbiaAbstract. Ghrelin, the endogenous ligand of growth hormone secretagogue receptor type 1a (GHS-R1a), has emerged as pleiotropic modulator of diverse biological functions, including energy homeostasis and recently, reproduction. Theinfluenceofintracerebroventricularly(ICV)adminis-tered ghrelin (1 μg/day/rat for 5 days) to rats of differentages,i.e.,peripubertal(38days),adult(60days) and middle-aged (180 days) on the ventral prostate size and morphology, serum testosterone levels and testis weight was examined. Ghrelin treatment significantlyincreased(p < 0.05) absolute ventral prostate weight in peripubertal and middle-aged rats, by 27% and 37% respectively, due to enhancement of epithelial and/or luminal compartment of the gland. In adult rats, both absolute and relative volumes of the acinar lumen were significantlydecreased(p < 0.05), by 38% and 44% respectively, which was associated with significantincreases(p < 0.05) in relative and absolute volumes of interacinar stroma, whereas ventral prostate weigh was unchanged. Irrespective of animal age, ghrelin did not affectserumtestosteronelevels.Thesearethefirstresultsof ghrelintreatmenteffectson healthy prostate appearance, which allow us to conclude that the rat ventral prostate response to ghrelin depends on the developmental stage of animals. Our results merit further investigations and may have clinical implications, especially in the light of data on possible role of ghrelin in prostate hypertrophy and adenomas. Key words: Ghrelin — Ventral prostate — Rats

Ghrelin, an endogenous ligand for the growth-hormone-secretagogue receptor, is a 28-amino acid peptide with a post-translational acyl modification necessary for its activity. It has central nervous system actions that affect appetite, body mass and energy balance. An intracerebroventricular (ICV) injection protocol of sub-nanomolar doses of ghrelin, known to alter the morphology of ACTH and GH producing pituicytes and plasma levels of these hormones, was used to provide an overview of metabolic changes linked to energy metabolism. Variables measured were: food intake (FI), water intake (WI), fecal mass, urine volume, body weight (BW), retroperitoneal (RP) and epididymal (EPI) white adipose tissue (WAT), and changes in serum leptin, insulin, triglycerides, cholesterol, and glucose. Five injections of rat ghrelin or PBS (n=8 per group) were given ICV every 24 h (1 microg/5 muL PBS) to adult male rats. Ghrelin had a positive and cumulative effect on FI, WI and BW (p0.05), but not feces mass or urine volume (p0.05). Centrally applied ghrelin clearly increased RP WAT (by 235%, p0.001), EPI WAT (by 85%, p0.05) and serum insulin levels (by 43%, p0.05), and decreased serum leptin levels (by 77%, p0.05) without (p0.05) evoking changes in blood triglyceride cholesterol, or glucose levels. These data and the available literature clearly document that exposure of the brain of normal rats, over time, to sub-nanomolar doses of ghrelin results in metabolic dysregulation culminating in increased body mass, consummatory behavior, and lipid stores as well as changes in blood leptin/insulin levels. Thus, modulation of central ghrelin receptors may represent a pharmacological approach for controlling multiple factors involved in energy balance and obesity.