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Introduction The main goal of this study was to evaluate the effect of nusinersen treatment in patients with spinal muscular atrophy (SMA) on cerebrospinal fluid (CSF) S100 calcium-binding protein B (S100B) levels. We were also interested in determining whether CSF S100B protein is associated with genetic biomarkers of SMA, scores on the Hammersmith Functional Motor Scale Expanded (HFMSE), and The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scales for the assessment of motor functions in SMA patients, as well as type and duration of SMA. Materials and Methods The study involved Thirty SMA patients at the University Hospital Centre Zagreb. Before administering nusinersen, CSF samples were obtained from patients via lumbar puncture. Using Enzyme-Linked Immunosorbent Assay (ELISA), the CSF S100B concentration was measured. We used the CHOP-INTEND and the HFMSE instruments to evaluate motor functions in SMA patients. The Multiplex Ligation-dependent Probe Amplification (MLPA) technique was utilized for all genetic analyses. SPSS version 19.0.1 (SPSS, Chicago, Illinois, United States) was used for statistical data analysis. Due to the non-normal distribution of the data, non-parametric tests were utilized. Results The levels of CSF S100B did not change significantly in SMA patients treated with nusinersen. In addition, there was no association between S100B levels and scores on the HFMSE and CHOP-INTEND scales or genetic biomarkers of SMA (the number of copies of the NAIP gene and the number of copies of the 7th exon of the SMN2 gene). The S100B levels of patients with distinct types of SMA were identical. However, S100B levels were positively correlated with disease duration. Discussion/Conclusion S100B protein did not exhibit the characteristics of an informative biological marker for the therapeutic response of patients with SMA during nusinersen therapy, as nusinersen administration had no effect on S100B levels. Also, no association between S100B protein and SMA genetic biomarkers was established. Nonetheless, S100B values were positively correlated with disease duration.

Introduction The purpose of this study was to examine the effect of nusinersen treatment on the concentration of total tau (t-tau) protein in cerebrospinal fluid (CSF) of patients with spinal muscular atrophy (SMA). SMA is an autosomal recessive disorder characterized by degeneration of the spinal cord anterior horn motoneurons, which is caused by homozygous deletion or mutation of the survival motor neuron 1 (SMN 1) gene. We also analyzed the association between CSF t-tau and genetic biomarkers of SMA (the number of copies of the 7th exon of the SMN2 gene and the number of copies of the NAIP gene), scores on measures for assessing motor functions, duration and type of SMA. Materials and Methods 30 patients with SMA types 1, 2, and 3 who were treated at the University Hospital Centre in Zagreb participated in the study. T-tau concentration in CSF was determined using Enzyme-Linked Immunosorbent Assay (ELISA) from lumbar puncture samples of CSF. Their motor function was measured using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) and the Hammersmith Functional Motor Scale Expanded (HFMSE). Using the Multiplex ligation-dependent probe amplification technique (MLPA), genetic analyses were conducted. SPSS version 19.0.1 was utilized for statistical data analysis (SPSS, Chicago, IL, USA). Results After treatment with nusinersen, CSF t-tau levels decreased significantly. There were no statistically significant differences in CSF t-tau levels between SMA patients with various genetic biomarkers. In addition, there was no correlation between t-tau levels and scores on the COOP-INTEND and HFMSE scales. There was no association between CSF t-tau and SMA duration or subtype. Discussion/Conclusion CSF t-tau protein proved to be a prognostic and theragnostic biological marker of a successful response in patients with SMA, as its average values decreased in a statistically significant manner following administration of nusinersen. However, t-tau did not correlate with genetic biomarkers of SMA, motor function assessment scale scores, disease duration, or disease type.

CAD is known as one of major cause of mortality in most industrialized countries. Evidence from epidemiological studies, clinical correlations, and genetic hyperlipidemias indicate that lipids play a key role in the pathogenesis of CAD. The known lipid related factors include high LDL-C, low HDL-C, high ApoB level and elevated concentration of Lp(a). Among the risk factors not related to lipids are those involved in either thrombosis like homocystein and fibrinogen, or in exposure of endothelial cells to oxidative stress and/or inflammation, as well as some newly recognized factors (low activity of paraoxonase or biologically active ontioxidants). Obesity associated with diabetes mellitus, hypertension, and sedentary life style add to the severity of the disease. In this multifactorial process it is important to understand the contribution of a single or a cluster of factors responsible for pathobiochemistry and epidemiology of CAD in different populations. This study was undertaken with the aim to evaluate thrombosis associated risk factors in CAD together with related gnetic lipid factors involved in atherosclerosis. Material: 297 patients aged 32-70 years of both sexes with angiographically confirmed atherosclerosis of varying severity, and a control group of 107 individuals of the same age with negative finding of coronary atherosclerosis. One half of CAD patients had positive history of MI. The severity of CAD was expressed by the number of affected vessels ond the presence of

Aim of this study was to assess diagnostic value of risk factors for atherosclerosis in patients with angiographically confirmed coronary obliteration. Also, correlation between the importance of coronarography findings and some risk factors was investigated. Material: 297 patients aged 32-70 years of both sex prior to coronaroplastics. Family history, RR-S and RR-D were included in patient examination. Laboratory analysis included measurement of serum concentration of cholesterol, LDL-C, HDL-C, HDL2/HDL3-C ratio, Lp(a), Apo AI, ApoB, ApoE and ACE activity. Plasma homocysteine, fibrinogen and platelet number were also determined. Molecular diagnosis, i.e. ApoE gene polymorphism and ACE gene deletion/insertion polymorphism, was performed on all patients while ApoB 3500 mutation and LDL-R gene analyses included hypercholesterolemic patients (LDL-C over 4.5 mmol/L). Multivariate analysis of these data confirmed the strongest correlation between coronarography findings and concentrations of Lp(a), triglycerides, fibrinogen and homocysteine. Patients with coronary atherosclerosis had pronounced ACE DD genotype and proportion of patients among them with Apo E 4/4 genotype was increased. LDL-R gene mutations were found on exons 4a, 4b, 8 and 10 in hypercholesterolemic patient group. Results are considered with regard to diagnostic value of individually or jointly determined parameters with the aim of recognizing individuals with high risk for developing coronary atherosclerosis.

The aim of this study was to assess diagnostic value of risk factors for atherosclerosis in patients with angiographically confirmed coronary obliteration. Also, correlation between the importance of coronarography findings and some risk factors was investigated...

Bradykinin receptor B2 gene (BDKRB2) is a candidate gene for the molecular marker of inherited predisposition to essential hypertension (EH). It encodes a G-protein linked receptor and there are four known polymorphic sites within the gene. In exon 2 the transition C>T at position 181 of cDNA results in substitution of arginine by cystein at codon 14 (R14C) of the protein. In the promoter region the transition T>C at position 58 upstream is possible, but its effects are still unknown. We investigated the association of these two polymorphisms with EH. The subjects were divided into two groups: normotensives (N=80) and hypertensives (N=80). The polymorphic sites were analysed using PCR/SSCP and RFLP. The C and T alleles at both sites were found to be in Hardy-Weinberg equilibrium and their frequencies were similar to those published for South German population. No significant differencies in the distribution of the genotypes between the two groups were found. Further analysis of the remaining two polymorphic sites is needed in order to rule out this gene as a molecular marker in EH.