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The hereditary spherocytosis is an inherited hemolytic anemia; it can be thecause of the hemolytic disease of nevvborns, infants and small children. The spherocytosisappears due to a defect in the structure of the specific plasma proteins ofthe erythrocyte membrane, that is, of the spectrin, and, as sometimes possible, of theankvrin as well. As a consequence of the intrinsic ("intracorpuscular") defect in themembrane, the erythrocytes at the hereditary spherocytosis, accumulate natrium ionsand water; thus, they become swollen and spherical two to three times than the normalerythrocytes. That is why they exhibit increased osmotic fragility and quickenedantihemolysis. The spherocytosis is most often revealed by perceiving the symptomsof the hemolytic anemia, that is, by the presence of anemia, indirect hyperbilirubinemia,a greater presence of natrium in the erythrocytes along with the simu-Itaneous reduction of the amount of kalium, the reduced osmotic resistance of theerythrocytes, mild hypersideremia and reticulocytosis in addition to the appearanceof spherocytes and splenomegaly. The paper presents the cases of three patients who,after being subjected to splenectomy, have shown the improvement of the generalstate as well as mitigation of the hemolytic anemia symptoms.

Purpose of Review: To elucidate the current approach of care in pediatric patients with familial hypercholesterolemia (FH). We sought an answer to the question whether the advances and major changes in lipid management are relevant and apply to children and adolescents. Recent Findings: Latest research findings clearly demonstrate that lowering cholesterol levels at a young age prevents vascular atherosclerotic changes and decreases cardiovascular events in adulthood and emphasizes the importance of early detection and intervention in the pediatric FH patients group. Summary: FH is a common genetic disease caused by mutations in genes associated with the metabolism of low-density lipoproteins (LDL). The hallmark of FH is elevated LDL cholesterol (LDL-C) levels from birth and premature atherosclerotic cardiovascular disease (ASCVD). Often FH is either undiagnosed or diagnosed with a considerable delay, leading to vascular atherosclerotic changes and cardiovascular disease. Prompt identification of FH subjects is essential, to initiate early preventive measures. Safe and efficient pharmacological agents are approved for use in children and adolescents. Statins are the first line of therapy, in combination of ezetimibe. Unfortunately, these drugs do not warrant the achievement of therapeutic target, especially in HoFH patient. In the latter, lipoprotein apheresis (LA), which has been shown to be safe and effective, is strongly recommended. Finally, the new drugs still under study will allow a multimodal customized treatment. Lowering cholesterol levels at a young age hinders vascular atherosclerotic changes decreasing cardiovascular events in adulthood. Therefore, early detection, diagnosis, and intervention in FH patients are priority objectives. [ABSTRACT FROM AUTHOR]

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease.The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

ObjectivePublished reports describing awareness and knowledge of familial hypercholesterolemia (FH) among pediatricians are few and differ considerably across countries. We aimed to assess awareness and knowledge of the FH among pediatricians in Serbia.MethodsA web-based cross-sectional study using a self-designed questionnaire was conducted during the annual congress of the Serbian Association of Preventive Pediatrics in 2020.ResultsA total of 141 pediatricians completed the questionnaire (response rate 16.1%). Overall, 91% of participants have knowledge about genetic inheritance of FH, 84.3% were aware of long-term health risks of FH, 77% were familiar with normal cholesterol values in children and 71% knew the FH prevalence in the general population. On the other hand, only 36.8% declared that they were familiar with international guidelines for FH drug treatment and only 26.2% declared to have patients with FH.ConclusionThere is a substantial lack of practical clinical knowledge among Serbian pediatricians on managing children with FH. In addition, an extremely low questionnaire response rate (16.1%) suggests that most pediatricians are not aware of the clinical importance of FH in childhood.

BackgroundLeft ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP with primary hypertension (PH).MethodsA meta-analysis of prevalence was performed. A literature search of articles reporting LVH in CYP with PH was conducted in Medline, Embase, and Cochrane databases. Studies with a primary focus on CYP (up to 21 years) with PH were included. Meta-regression was used to analyze factors explaining observed heterogeneity.ResultsThe search yielded a total of 2,200 articles, 153 of those underwent full-text review, and 47 reports were included. The reports evaluated 51 study cohorts including 5,622 individuals, 73% male subjects, and a mean age of 13.6 years. LVH was defined as left ventricle mass index (LVMI) ≥ 95th percentile in 22 (47%), fixed cut-off ≥38.6 g/m2.7 in eight (17%), sex-specific fixed cut-off values in six (13%), and miscellaneously in others. The overall prevalence of LVH was 30.5% (95% CI 27.2–33.9), while heterogeneity was high (I2 = 84%). Subgroup analysis including 1,393 individuals (76% male subjects, mean age 14.7 years) from pediatric hypertension specialty clinics and LVH defined as LVMI ≥95th percentile only (19 study cohorts from 18 studies), reported prevalence of LVH at 29.9% (95% CI 23.9 to 36.3), and high heterogeneity (I2 = 84%). Two studies involving patients identified through community screening (n = 1,234) reported lower LVH prevalence (21.5%). In the meta-regression, only body mass index (BMI) z-score was significantly associated with LVH prevalence (estimate 0.23, 95% CI 0.08–0.39, p = 0.004) and accounted for 41% of observed heterogeneity, but not age, male percentage, BMI, or waist circumference z-score. The predominant LVH phenotype was eccentric LVH in patients from specialty clinics (prevalence of 22% in seven studies with 779 participants) and one community screening study reported the predominance of concentric LVH (12%).ConclusionLeft ventricular hypertrophy is evident in at least one-fifth of children and young adults with PH and in nearly a third of those referred to specialty clinics with a predominant eccentric LVH pattern in the latter. Increased BMI is the most significant risk association for LVH in hypertensive youth.

Abstract Background Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the relationship between serum lipid levels and left ventricular geometry pattern. We sought to explore the relationship between standard serum lipid profile measures with left ventricular geometry pattern in obese children. Patients and methods In this cross-sectional study, a total of 70 obese children were examined. Fasting blood samples were taken to measure total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), glucose, and insulin. Based on these values TG/HDL ratio, BMI and HOMA index were calculated. We also measured the average 24-h ambulatory systolic blood pressure (SBP) and two-dimensional (2/D) transthoracic echocardiography was performed to determine left ventricular mass index (LVMI) and relative wall thickness (RWT). Multiple regression analyses were conducted to explore relationships between study variables and the LVMI or RWT as outcome variables. The final model with LVMI included TG/HDL ratio, BMI, 24 h-average SBP, age and sex, while for the RWT we included BMI, insulin, age and sex. Results Our study included 70 children (65.71% boys and 34.29% girls) median age (14 years, IQR = 12–16)." We demonstrated independent and positive association of TG/HDL ratio, BMI and 24 h-average SBP with LVMI (effect = 3.65, SE = 1.32, p

Reynolds Risk Score (RRS) is regarded as a good screening tool for cardiovascular disease (CVD) risk. Since CVD is the leading cause of death in Montenegro, we aimed to assess the risk of CVD as assessed by RRS and to examine its association with cardiometabolic parameters in apparently healthy middle-aged population. In addition, we aimed to test whether obesity had an independent influence on RRS. A total of 132 participants (mean age 56.2±6.73 years, 69% females) were included. Body mass index (BMI), waist circumference (WC), blood pressure (BP) and biochemical parameters (fasting glucose, insulin, lipid parameters, creatinine and high sensitivity C-reactive protein) were determined. Insulin resistance (HOMA-IR) and glomerular filtration rate (eGFR) were calculated. Compared with females, a significantly higher number of males were in the high RRS subgroup (χ2=45.9, p

Abstract: The binding of acetaminophen to bovine serum albumin (BSA) was studied by the quenching fluorescence method and the proton nuclear magnetic resonance technique (1H NMR). For fluorescence measurements 1-anilino-9-naphthalene sulfonate (ANS) hydrophobic probe was used to verify subdomain IIIA as acetaminophen’s likely binding site. Three binding sites of acetaminophen in subdomain IIA of bovine serum albumin were found. Quenching constants calculated by the Stern–Volmer modified method were used to estimate the influence of myristic acid (MYR) on the drug binding to the albumin. The influence of [fatty acid]/[albumin] molar ratios on the affinity of the protein towards acetaminophen was described. Changes of chemical shifts and relaxation times of the drug indicated that the presence of MYR inhibits interaction in the AA–albumin complex. It is suggested that the elevated level of fatty acids does not significantly influence the pharmacokinetics of acetaminophen. [Copyright &y& Elsevier]

Abstract: Saturated fatty acids such as myristic acid play an important role in the pathogenesis of cardiovascular disorders. Using the quenching fluorescence method we examined the influence of myristate on the changes of transporting protein affinity towards aspirin—the most popular anticoagulant. Our results showed that the presence of the myristic acid alters the stability of the anticoagulant–albumin complex. The ranges of [myristate]/[albumin] molar ratio at which the stability of drug–protein complex increases or decreases were determined. The differences in interaction between ligands and human or bovine serum albumins were identified. The competition in binding of ligands with these albumins was also described. [Copyright &y& Elsevier]

The protoporphyrin (PPIX) incorporated liposomes were prepared and the change of PPIX UV-Vis spectra in this system were analyzed. The effect of serum albumin (BSA) on the lipo-PPIX system has been presented. Different changes in absorbance of peaks I (at ? max 279 nm) and II-V, observed in the lipo-PPIX spectrum in the presence of BSA, suggest that PPIX associated with liposome exists in two different microenvironments, i.e., hydrophobic and polar. The latter is located near the membrane surface close to the polar phospholipid head. The release of the PPIX from these sites is not observed in the presence of BSA. Time dependence of the spectral properties of solution PPIX in water has been presented. It was found that BSA forms a complex with PPIX at PPIX/BSA molar ratio 0.2/1. [ABSTRACT FROM AUTHOR]

Retinol-binding protein 4 (RBP4) is an emerging risk factor for atherosclerotic disease in adults. However, to our knowledge,there are no studies examining the relationship between RBP4 and cardiovascular risk in young population. Th erefore, we aimed to estimate this potential relationship in overweight/obese adolescent girls. Seventy overweight/obese adolescent girls, mean age 17.6±1.20 years, were included. Anthropometric and biochemical parameters were measured. Cardiovascular risk score (CVRS) was calculated by adding points for each risk factor (e.g., sex, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, smoking, blood pressure and fasting glycemia). According to the risk status, we divided adolescent girls into low, medium and high risk groups (-2≤ CVRS ≤1, 2≤ CVRS ≤4 and CVRS ≥5, respectively). We found significantly higher RBP4 in the high risk group as compared with low risk group (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 ≥ 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: 2−15) than those treated with colchicine (0, IQR: 0−0.75). Conclusions: Independent risk factors for recurrence are CS treatment, viral aetiology, pericarditis only and ESR ≥ 50 mm/h. Acute pericarditis should be treated with NSAID. Colchicine and NSAID might be recommended in children with the first ROP.

The dynamic of enzyme activities in human colostrum and milk changes, depending on the lactation stimulation. The aim of the study was to study the activity of alkaline phosphatase, amylase, transaminases (ALT and AST) and lactate dehydrogenase (LDH) in the samples of human colostrum and mature milk obtained by manual squeezing. The study involved 35 women, 18-39 years of age, who had given birth at the Clinic for Gynecology and Obstetrics, Faculty of Medicine in Niš, with normal delivery, without any complications reported. The samples of colostrum and milk were collected by mechanical squeezing of milk during three intervals: the first sample of colostrum was obtained immediately after the appearance of the first drops of milk after childbirth; the second sample was obtained after 24 hours, and the third after one month. The samples were collected in the morning, and kept in sterile test tubes in the freezer until the performance of analysis. The activity of these enzymes was reduced (statistically significant for amylase) in the period after one month, which means that it corresponded to the amount of protein. The activity of transaminases (ALT and AST) and alkaline phosphatase activity showed a tendency to fall after a month, but statistically significant difference was obtained with AST. The dynamic of alkaline phosphatase activity showed statistically significant decrease after one month. Enzyme activity in human milk represents an important field of research, from the aspect of functional importance and benefits of human milk compared to the cow’s milk, in which enzymes are generally destroyed by pasteurization. On the other hand, increased activity of certain enzymes may be a useful and valid diagnostic marker of mechanical tissue irritation, epithelial desqamation and increase of the concentration of inflammatory cells during mastitis.

Adipose tissue is not only the main organ for energy storage, but it also has endocrine properties, producing “adipokines” responsible for energy homeostasis, insulin sensitivity, and inflammation. Leptin, produced by adipocytes, is the key hormone in appetite regulation and suppression of orexigenic, hypothalamic neuropeptide Y (NPY). We wanted to establish and compare levels of leptin and NPY in different obesity types in childhood, and to investigate their correlations with auxological parameters. Twenty-one obese children (seven girls and 14 boys), divided into two groups, were compared with 14 controls. The mean age of the study group was 10.81 ± 3.69 years and the mean puberty stage was 2.21. The mean body mass index (BMI) was 32.80 kg/m2 (range 23.30– 47.02) and the mean overweight 30.73 kg (range 8.00–74.00). The mean leptin level was higher in boys and in the group with central obesity, but was not significant. Leptin/NPY ratio and leptin/BMI ratio was also higher in the central obesity group and there was a more significant difference compared with controls. We found significant correlation of the leptin level with body mass (BM), body mass excess (BME), and BMI (p < 0.05). The mean leptin level in obese children was very high (36.39 ng/ml). Leptin and NPY levels showed inverse values in two different obesity types. Results are suggestive for leptin resistance rather than leptin deficiency in our group of obese children. Orexitropic signaling proteins correlated significantly with auxological parameters. Determination of the leptin and NPY concentrations provided evidence that obesity represents disease with neuroendocrine dysfunction and high leptin/NPY ratio, which could be a useful marker for central obesity.

Letter to the Editor

This is a case story of an 8-year-old boy with no prior history of cardiac disease who developed acute pulmonary edema with ECG changes similar to transmural myocardial infarction after basilar skull fracture. Biochemical evaluation showed elevated total creatine kinase activity –1,350 U/L with 12% MB isoenzyme fraction. The brain scan on admission showed cerebral edema with ethmoidal sinuses hemorrhage. Neurogenic pulmonary edema following CNS damage is an extremely rare entity in the pediatric population and there are few reports. There are many proposed mechanisms and explanations of its origin. Based on previous reports and experimental studies, the cause of “neurogenic” pulmonary edema may be of cardiac as well as of noncardiac origin.

Pteridines are widely distributed compounds in nature, associated with numerous important physiological functions. BH4 is classified as unconjugated pteridine distinct from folic acid and its metabolites folates representing the group of conjugated pteridines. Unlike folic acid, which is a vitamin, BH4 can be synthesized in organism.Tetrahydrobiopterin (BH4) is a cofactor, important for different biological processes, present in probably all cells and tissues of higher organisms. The presence of persistent hyperphenylalaninemia with atypic neurological symptoms in children, resistent to diet poor in phenylalanin, which disappears upon BH4 application, gave a strong impuls to the study of this unconjugated pteridine metabolic functions.BH4 is a natural cofactor of cyclic amino acid hydroxylases - phenylalanin hydroxylase (EC 1.14.16.2), tyrosine-3-hydroxylase (EC 1.14.16.3) and tryptophane-5-hydroxylase (EC 1.14.16.4) as well as all three isoenzymes of nitric oxide synthase (NOS). It is neccessary for the activity of glyceryl-ether-monooxygenase (1.14.16.5). The regeneration of tetrahydrobiopterin is neccessary for the catalytic activity of these enzymes.BH4 insufficiency disturbs the function of mentioned hydroxylases leading to disorders of their products synthesis, especially 5-hydroxytryptophane, the precursor of serotonine and L-DOPA (the precursor of catecholamines). These metabolites function as neurotransmitters in brain and their deficit causes CNS diseases (including disturbed psychomotoric development, disfunction of basal ganglia and instability of body temperature. The whole content of BH4 present in organism originates from de novo synthesis of this compound.Tetrahydrobiopterin deficit disturbs the function of all three isoenzymes of NOS: NOS-I or neuronal, macrophagal or inducible (NOS-II) and endothelial (NOS-III), leading to decreased production of NO and increased production of superoxide anion. The inhibition of GTP cyclohydrolase 1 (GCH 1), the key enzyme in tetrahydrobiopterin biosynthesis, which uses exclusively magnesium-free GTP as substrate, lessens vasodilation and causes increase of blood pressure.Tetrahydrobiopterin is neccessary in the prevention of blood vessel damage and for normal function of endothelial cells in diabetes. BH4 regulates normal proliferation of endothelial cells (EC), which produce NO under the influence of NOS-III. The result of decreased NO production by endothelial cells in diabetes is disturbed angiogenesis, which directly depends on BH4 level, as a cofactor of nitric oxide synthesis.It is a very interesting fact that this cofactor is synthesized from GTP, nucleoside triphosphate also neccessary for the synthesis of proteins, as well as for the functioning of adenyl cyclase system, needed for the production of cAMP, secondary messenger neccessary for adrenalin, glucagon and other hormones action.The stimulation of tetrahydrobiopterin synthesis by cytokines undoubtly points out biological functions of pteridines in organism immune response.Tissue distribution of BH4 indicates the fact that renal tissue is the richest in this metabolite compared to brain and liver tissue; it calls for the need of investigating BH4 physiological functions in kidney.The importance of BH4 in tyrosine production (neccessary for the synthesis of thyreoid gland hormones, T3 and T4, the production of neurotransmitters - DOPA, dopamine, noradrenalin), synthesis of serotonine and melatonine, the function of endothelial cells by production of NO, normal angiogenesis, maintaining of normal blood pressure, points out further directions of the investigation of biological functions of this very important cofactor of intermediary metabolism.

Until recent advances in pharmacology and clinical cardiology regarding farmacodynamics of antiarrhythmic drugs and their efficiency in patients with refractory paroxysmal supraventricular tachycardia, chronic prophylactic therapy was the only treatment option for patients refusing catheter ablation. Another treatment option, also known by eponym “pill in pocket” have been shown to be equally useful and efficacious.The aim of our study was prospective examination of children with refractory atrioventricular nodal reentry tachycardia (AVNRT) who were withdrawn from chronic antiarrhythmic prophylactic therapy and started with intermittent oral beta blocker treatment (propranolol at dosage 1 mg/kg - max 80 mg).Twelve children (8 boys and 4 girls) with AVNRT were included in the study. Four children did not have arrhythmia during first six months after withdrawal and 7 were successfully treated without complication.Intermittent antiarrhythmic therapy in children with AVNRT could be very efficacious and useful treatment option which significantly improves their quality of life.

Abstract: Rheumatoid arthritis (RA) is an immunologically depended disease. It is characterized by a chronic, progressive inflammatory process. Methotrexate (4-amino-10-methylfolic acid, MTX) is the modifying drug used to treat RA. The aim of the presented studies is to determine the low affinity binding site of MTX in bovine (BSA) and human (HSA) serum albumin with the use of proton nuclear magnetic resonance (1HNMR) spectroscopy. The analysis of 1HNMR spectra of MTX in the presence of serum albumin (SA) allows us to observe the interactions between aromatic rings of the drug and the rings of amino acids located in the hydrophobic subdomains of the protein. On the basis of the chemical shifts σ [ppm] and the relaxation times T 1 [s] of drug protons the hydrophobic interaction between MTX–SA and the stoichiometric molar ratio of the complex was evaluated. This work is a part of a spectroscopic study on MTX–SA interactions [A. Sułkowska, M. Maciążek, J. Równicka, B. Bojko, D. Pentak, W.W. Sułkowski, J. Mol. Struct. 834–836 (2007) 162–169]. [Copyright &y& Elsevier]

Abstract: The influence of phenylbutazone (Phe) and methotrexate (MTX) on binding of MTX and Phe to human (HSA) and bovine (BSA) serum albumin in the low-affinity binding sites is investigated. The strength and kind of interactions between serum albumin (SA) and drugs used in combination therapy were found using 1H NMR spectroscopy. A stoichiometric molar ratios for Phe–SA and MTX–SA complexes are 36:1 and 31:1, respectively. It appeared these molar ratios are higher for the ternary systems than it were in the binary ones. The presence of the additional drug (MTX or Phe) causes the increase of an affinity of albumin towards Phe and MTX. It was found that the aliphatic groups of MTX are more resistant to the influence of Phe on the MTX–SA complex than the aromatic rings. The results showed the important impact of another drug (MTX or Phe) on the affinity of SA towards Phe and MTX in the low-affinity binding sites. This work is a subsequent part of the spectroscopic study on Phe–MTX–SA interactions (Maciążek-Jurczyk, 2009 ). [Copyright &y& Elsevier]