Cerebrospinal Fluid Biomarkers in the Diagnosis of Creutzfeldt-Jakob Disease in Slovak Patients: over 10-Year Period Review.

Creutzfeldt-Jakob disease is a rare, but rapidly progressive, up to now untreatable and fatal neurodegenerative disorder. Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is difficult; however, it can be facilitated by suitable biomarkers. Aim of the present study is to compare levels of cerebrospinal fluid biomarkers (total tau protein, phosphorylated-tau protein, protein 14-3-3 and amyloid beta) in Slovak population of CJD suspect cases, retrospectively in over a 10-year period. One thousand three hundred sixty-four CSF samples from patients with suspect CJD, forming a homogenous group in terms of geographical as well as of equal transport conditions, storage and laboratory processing, were analysed. Definite diagnosis of Creutzfeldt-Jakob disease was confirmed in 101 patients with genetic form, and 60 patients with its sporadic form of the disease. Specificity of protein 14-3-3 and total tau in both forms CJD was similar (87 % for P14-3-3/85 % for total tau), sensitivity to P 14-3-3 and total tau was higher in sporadic Creutzfeldt-Jakob disease (sCJD) (90/95 %) than in genetic Creutzfeldt-Jakob disease (gCJD) (89/74 %). As expected, the total tau levels were significantly higher in CJD patients than in controls, but there was also significant difference between gCJD and sCJD (levels in gCJD were lower; p = 0.003). There was no significant difference in p-tau and Aß 1-42 levels neither between both CJD forms nor between CJD patients and control group.

The effect of obstructive sleep apnea on QRS complex morphology.

BACKGROUND: Obstructive sleep apnea (OSA) has been reported to be associated with an increased risk of ventricular arrhythmias and conduction disturbances. The aim of this study was to analyze the QRS complex morphology potentially indicative of intraventricular conduction impairment in patients with mild to severe OSA. MATERIAL AND METHODS: One hundred ninety-three consecutive patients, who underwent complete overnight polysomnography, were divided into four groups based on the OSA severity: (1) no OSA, (2) mild OSA, (3) moderate OSA and (4) severe OSA (apnea-hypopnea index <5, 5-15, 15-30, >30/h, respectively). Resting 12-lead ECG was recorded, the QRS parameters included QRS amplitude in individual leads, QRS spatial vector magnitude (QRSmax), electrical axis (EA), ECG criteria for left ventricular hypertrophy (ECG-LVH) and right ventricular hypertrophy (ECG-RVH), and occurrence of fragmented QRS (fQRS). RESULTS: Severity of OSA was significantly associated with a gradual significant shift of the electrical axis to the left (45.5±22.5°; 34.8±17.1°; 32.9±18.2°; 29.8±10.0°; respectively), while the QRSmax values were low in all patient groups, with a significant difference between no OSA and severe OSA groups. The multivariate analysis showed that QRSmax was independently associated with age and the interaction between gender and OSA severity (p=0.001, and p=0.004, respectively; adjusted R(2)=0.178). The electrical axis was found to be independently associated with age and OSA severity (p=0.037, and p=0.026, respectively; R(2)=0.109). Changes of electrical axis and of QRSmax were reflected in corresponding changes in the amplitude of 12-lead ECG and in low occurrence of ECG-LVH and ECG-RVH criteria. The OSA groups had higher occurrence of fQRS. CONCLUSION: OSA patients displayed a combination of changes in QRS complex morphology, the leftward shift of EA, low QRS voltage and fQRS, suggestive of depolarization sequence deterioration that might be indicative of considerable electrical remodeling.

Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase.

Structurally diverse, sugar-modified, thymine-containing nucleoside phosphonic acids were evaluated for their ability to inhibit thymidine phosphorylase (TP, EC 2.4.2.4) purified from spontaneous T-cell lymphomas of an inbred Sprague-Dawley rat strain. From a large set of tested compounds, among them a number of pyrrolidine-based derivatives, 10 nucleotide analogues with IC(50) values below 1 microM were selected. Out of them, four compounds strongly inhibited the enzyme with IC(50) values lying in a range of 11-45 nM. These most potent compounds might be bi-substrate analogues.