Ljiljana Saranac

Glucocorticoids and oxidative stress.

Glucocorticoids (GC) are used widely for the treatment of patients with various disorders, including autoimmune diseases, allergies, and lymphoproliferative disorders. Glucocorticoid therapy is often limited by several adverse reactions associated with GC excess. Excess GC can elicit a variety of symptoms and signs, including growth retardation in children; immunosuppression; cardiovascular disorders like hypertension and atherosclerosis; osteoporosis; myopathy; and diabetes mellitus. Currently, attention is focused on oxidative stress as one of the major determinants of endothelial dysfunction and cardiovascular senescence. The main reason for all unwanted effects of GC is that dexamethasone induces the overproduction of reactive oxygen species, causing dysregulation of physiological processes. Humans and animals with GC-induced hypertension exhibit reduced nitric oxide levels; patients with excess GC levels also suffer from depression as a consequence of low levels of serotonin and melatonin. The common cofactor for the production of these vasoactive molecules is tetrahydrobiopterin (BH4), which is required for nitric oxide synthesis.

Orexitropic Signaling Proteins in Obese Children

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/m (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.

The therapeutic efficacy of propranolol in children with recurrent primary epistaxis

We hypothesized that some characteristics of beta-blockers, including negative inotropic, peripheral vasoconstrictor, and antiangiogenic effects, might be potentially useful in treating children with epistaxis. From June 2010 to March 2012, a total of seven children with recurrent primary epistaxis resistant to conventional management were observed at our institution. An overall effectiveness of propranolol was noted in all seven children when given a dose of 1.5–2 mg/kg/day (divided into three doses) as a second line therapy for terminating epistaxis. Based on our first experience, we believe that propranolol could be a favorable treatment option for patients with primary epistaxis.

Possible impact of plasma RNase activity on immune dysfunction in juvenile diabetes mellitus

Aim:  The ribonuclease (RNase) family represents important enzymes used widely in biomedical and biotechnological applications, as well as for diagnostic and therapeutic purposes. This study was undertaken to test the possibility that plasma alkaline RNase (free or inhibitory bound) determination may be useful in studying the dysregulation of nucleic acid and oligonucleotide metabolism as a possible pathogenetic mechanism in development of immune dysfunction in juvenile diabetes mellitus.

A Case of Acute Tuberculous Pleuropneumonia in a Patient with Acute Lymphoblastic Leukemia

Respiratory system infections are the most common complications in immunocompromised cancer patients. We here report a 14-year-old male who was admitted to the hospital because of acute pneumonia, who had been diagnosed with acute lymphoblastic leukemia (ALL) when he was 12 years old. A diagnosis of acute tuberculous pleuropneumonia was made based on clinical and radiographical findings, and Mycobacterium tuberculosis was identified by Ziehl-Neelson acid-fast stain and culture on Löwenstein-Jensen medium. Twenty months before pneumonia onset, the patient had been treated with immunosupressive therapy (ALL IC-BFM 2002 protocol).

ECG Changes in 8-Year-Old Boy with Pulmonary Edema after Head Injury

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.

Growth in Children with Thyroid Dysfunction

Thyroid hormones (TH) are critical for early brain development, somatic growth, and bone and pubertal maturation. Moreover, they are crucial for survival, both in rodents and humans. In many respects, (TH) may be viewed as tissue growth factors. Effects on growth and development are classified as genomic actions mediated via stimulation of mRNA for pituitary growth hormone (GH) synthesis, secretion and sensitivity. TH potentiate GH stimulation of the synthesis and action of insulin-like growth factor 1 (IGF1) and stimula‐ tion of the production of different growth factors (epidermal growth factor, nerve growth factor, and erythropoietin). Cartilage response to IGF1 and osteoblastic/osteoclastic bone remodeling are also regulated by thyroid hormones. Unlike insulin and cortisol levels, which fluctuate widely in response to food ingestion and stress, thyroid hormones are typically maintained at a constant level that keeps the metabolic machinery functioning at a proper rate (Zimmerman-Belsing et al., 2003).

Heart rate variability in children with idiopathic ventricular tachycardia

Idiopathic ventricular tachycardia (IVT) is a rare arrhythmia in children. A great deal of uncertainty and numerous questions still remain regarding the extent of investigation, therapy, and long-term prognosis for children with IVT. The existence of subclinical cardiac disease, as well as of autonomic dysfunction in patients with ventricular arrhythmias, has been well documented. A number of experimental and clinical studies have suggested that imbalances within the cardiac autonomic system’s activity may be crucial in the generation of ventricular tachycardia, irrespective of the presence of cardiovascular pathological substrate. Heart rate variability (HRV) analysis provides a useful method for measuring the autonomic activity. This study evaluates HRV in children with IVT. The study included 31 children with ventricular arrhythmia who were divided into two groups: (1) patients with frequent ventricular extrasystoles (VES) and (2) patients with IVT. The control group comprised 23 healthy children without pathological findings on 24-h ECG Holter. Twenty-four-hour ambulatory electrocardiography recordings were obtained, and the time-domain variables were calculated. HRV was compared to age-related normal values. It was observed that the overall heart rate variability is diminished in children with IVT. We recommend HRV analysis of any child with IVT. Quantification of the autonomic nervous system activity using time domain analyses may be a helpful diagnostic tool in the clinical assessment and initial evaluation of these children.

Deep nasopharyngeal aspiration as a treatment option for conversion of supraventricular paroxysmal tachycardia in infants: First experiences.

Objective: Supraventricular paroxysmal tachycardias are the most common paroxysmal rhythm disorders in childhood. Atypical clinical presentations as well as their ability to induce hemodynamic deterioration imply necessity for arrhythmia rapid termination during the first months of life. The objective of this article was to evaluate the efficiency of deep nasopharyngeal aspiration as a potential vagal maneuver for supraventricular paroxysmal tachycardias termination. Design: Clinical trial. Patients and Methods: From June 2005 to October 2009, a total of eight infants, who were admitted at our institutions and diagnosed to have supraventricular paroxysmal tachycardias, were analyzed. To terminate supraventricular paroxysmal tachycardias “diving” reflex was initially tried and in the cases of its inefficacy, deep nasopharyngeal aspiration was performed. Main Results: Nasopharyngeal aspiration successfully converted arrhythmia in three infants (37.5%). Conclusions: Deep nasopharyngeal aspiration could be an alternative vagal maneuver for infants with supraventricular paroxysmal tachycardia.

Circulating nucleic acids in type 1 diabetes may modulate the thymocyte turnover rate

The autoimmunity of type 1 diabetes is associated with T-cell hyperactivity. Current study was designed to examine the effect of circulating ribonucleic acids (RNAs), isolated from type 1 diabetic patients on proliferative, apoptotic and inflammatory potential of rat thymocytes. Rat thymocytes were assayed for proliferating nuclear cell antigen (PCNA), Bcl-2, Bax and NF-κB level, using the flow cytometric and fluorometric assays. Cells were allocated into groups, treated with RNAs purified from plasma of juvenile diabetics, adult type 1 diabetic patients, control healthy children, healthy adult persons, nucleic acids and polynucleotide standards (RNA, polyC, PolyA, PolyIC, and CpG). The upregulation of PCNA and Bcl-2 protein and downregulation of Bax protein and NF-κB was shown when the thymocytes where incubated with RNA purified from plasma of juvenile type 1 diabetic patients. The dysregulation of inflammatory cascade and central tolerance may be a defect in autoimmune diseases related to innate immunity leading to corresponding alteration in adaptive immune response.