QT dispersion in patients with systemic lupus erythematosus: the impact of disease activity

<p>Abstract</p> <p>Background</p> <p>Patients with systemic lupus erythematosus (SLE) have increased cardiovascular morbidity and mortality. Although autopsy studies have documented that the heart is affected in most SLE patients, clinical manifestations occur in less than 10%. QT dispersion is a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function. We compared the increase in QT dispersion in SLE patients with high disease activity and mild or moderate disease activity.</p> <p>Methods and Results</p> <p>One hundred twenty-four patients with SLE were enrolled in the study. Complete history and physical exam, ECG, echocardiography, exercise test and SLE disease activity index (SLEDAI) were recorded. Twenty patients were excluded on the basis of our exclusion criteria. The patients were divided to two groups based on SLEDAI: 54 in the high-score group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10).</p> <p>QT dispersion was significantly higher in high-score group (58.31 ± 18.66 vs. 47.90 ± 17.41 respectively; <it>P </it>< 0.004). QT dispersion was not significantly higher in patients who had received hydroxychloroquine (54.17 ± 19.36 vs. 50.82 ± 15.96, <it>P </it>= 0.45) or corticosteroids (53.58 ± 19.16 vs. 50.40 + 11.59, <it>P </it>= 0.47). There was a statistically significant correlation between abnormal echocardiographic findings (abnormalities of pericardial effusion, pericarditis, pulmonary hypertension and Libman-Sacks endocarditis) and SLEADI (<it>P </it>< 0.004).</p> <p>Conclusions</p> <p>QT dispersion can be a useful, simple noninvasive method for the early detection of cardiac involvement in SLE patients with active disease. Concerning high chance of cardiac involvement, cardiovascular evaluation for every SLE patient with a SLEDAI higher than 10 may be recommended.</p> <p>Trial registration</p> <p>Clinicaltrial.gov registration <a href="http://www.clinicaltrials.gov/ct2/show/NCT01031797">NCT01031797</a></p

Quantum chemical studies on some 1-selena-cyclopenta[b] naphthalene-3-one derivatives

An AM1 (restricted Hartree-Fock) type semiempirical quantum chemical study has been performed on certain series of Se containing fused ring systems, which possess a Se atom in a five-membered ring system at beta-position to a keto group. The substituents are at any of peri-positions of the adjacent aromatic ring such that, due to the topology of the system, the substituent in one case are nearby the Se atom and in the other case nearby the C=O group. The study shows that all the systems are to be stable. Generally, the structures of the first type are more stable than their isomeric compounds of second type. Some other quantum chemical properties of these systems beside their energetics have been reported

3,3-dichloro-1,4-diphenylazetidin-2-one

kabak, mehmet/0000-0001-6097-9394WOS: 000082969100053In the crystal structure of the title compound, C15H11C12NO, the Cl-C-Cl plane is nearly perpendicular to the four-membered beta-lactam ring [89.0 (2)degrees] and the C-C bond distances in this group are 1.571 (6) and 1.543 (7) Angstrom. The most out-of-plane atom from the best plane of the lactam ring is the carbonyl C atom [-0.029 (5) Angstrom]. The dihedral angle between the best planes of the phenyl rings is 77.4 (2)degrees

3,3-Dichloro-1-(p-chlorophenyl)4-(p-methoxyphenyl)-2-azetidinone

kabak, mehmet/0000-0001-6097-9394WOS: 000085284600071The crystal structure of the title compound, C16H12Cl3NO2, has a nearly planar beta-lactam ring with the N atom out of the best plane by 0.032(2) Angstrom. The C-C bond distances in the beta-lactam ring are 1.544(4) and 1.568(4) Angstrom. The chlorophenyl and methoxyphenyl rings are nearly perpendicular to one another [81.92(7)degrees]

1-Methoxy-3-o-tolylbicyclo[2.2.2]oct-5-ene-2,2-dicarbonitrile

In the title compound, C18H18N2O, the cyclohexene and cyclohexane rings of the bicyclo[2.2.2]oct-5-ene unit adopt distorted boat conformations. In the crystal, molecules exist as C-H center dot center dot center dot N hydrogen-bonded centrosymmetric R-2(2)(14) dimers, which are further linked by C-H center dot center dot center dot pi interactions

fingolimod used in the treatment of multiple sclerosis

Multiple sclerosis (MS) is a very common disease of vital importance. In the MS treatment, some drugs such as fingolimod which help to protect nerves from damage are used. The main goal of the drug therapy in MS is to take control of the inflammation which leads to the destruction of myelin and axons in nerve cell and thus prevent and stop the progression of the disease. Fingolimod (FTY720) is an orally active immunomodulatory drug that has been used for the treatment of relapsing-remitting multiple sclerosis. It is a sphingosine-1-phosphate receptor modulator which prevents lymphocytes from contributing to an autoimmune reaction by inhibiting egress of lymphocytes them from lymph nodes. In this study, we have computer designed, synthesized and characterized two novel derivatives of FTY720, F1-12h and F2-9, and have determined their underlying mechanism of their beneficial effect in SH-SY5Y, SK-N-SH, and U-118 MG cell lines. For this purpose, we first determined the regulation of the cAMP response element (CRE) activity and cAMP concentration by F1-12h and F2-9 together with FTY720 using pGL4.29 luciferase reporter assay and cAMP immunoassay, respectively. Then, we have determined their effect on MS-and GPCR-related gene expression profiles using custom arrays along with FTY720 treatment at non-toxic doses (EC10). It was found that both derivatives significantly activate CRE and increase cAMP concentration in all three cell lines, indicating that they activate cAMP pathway through cell surface receptors as FTY720 does. Furthermore, F1-12h and F2-9 modulate the expression of the pathway related genes that are important in inflammatory signaling, cAMP signaling pathway, cell migration as well as diverse receptor and transcription factors. Expression of the genes involved in myelination was also increased by the treatment with F1-12h and F2-9. In summary, our data demonstrate that the two novel FTY720 derivatives act as anti-inflammatory ultimately by influencing the gene expression via the CAMP and downstream transcription factor CRE pathway. In conclusion, F1-12h and F2-9 might contribute future therapies for autoimmune diseases such as multiple sclerosis. (C) 2016 Elsevier Ltd. All rights reserved

Qt Dispersion As A Predictor of Arrhythmic Events in Patients with Ankylosing Spondylitis

Objective. The aim of the study was to evaluate QT dispersion (QTd), an indicator of repolarization heterogeneity, and its relation to ventricular arrhythmias in patients with ankylosing spondylitis (AS). Methods. A full history, clinical examination, electrocardiograms and 24-h Holter monitoring were performed in 88 AS patients and 31 volunteers of similar age and sex. Groups were compared based on electrocardiographic abnormality, QTd, arrhythmias and heart blocks. Results. QTd and corrected QTd (QTcd) were significantly greater in AS patients than controls (QTd, 52.8 +/- 15.1 vs 35.5 +/- 8.9 ms, P < 0.0001; QTcd, 60.3 +/- 16.1 vs 39.4 +/- 10.7 ms, P < 0.0001). The magnitudes of these parameters were associated with the duration of the disease (QTd, r = 0.56, P < 0.01; QTcd, r = 0.60, P < 0.001). The frequency of ventricular extrasystoles was found to be correlated with QTd (r = 0.35, P < 0.01) and QTcd (r = 0.33, P < 0.01). Conclusion. Involvement of the heart may be seen in AS during the early clinical course of the disease. QTd may give clues about the presence of arrhythmias and can be used as a new technique for the evaluation of asymptomatic patients. Earlier detection of cardiac involvement could alter the prognosis of the patients.WoSScopu

Cladribine-Like Compounds for the Treatment of Multiple Sclerosis

Cladribine (2-CdA) is used as an anti-cancer drug but is currently studied as a potential treatment for use in relapsing-remitting multiple sclerosis (MS). In this study, we computer designed, synthesized, and characterized two novel derivatives of 2-CdA, K1-5d and K2-4c, and investigated their underlying mechanism of beneficial effect using the CCRF-CEM and RAJI cell lines. For this purpose, we first determined their effect on MS and DNA damage and repair-related gene expression profiles using custom arrays along with 2-CdA treatment at non-toxic doses. Then, we determined whether cells underwent apoptosis after treatment with 2-CdA, K1-5d, and K2-4c in CCRF-CEM and RAJI cells, using the DNA fragmentation assay. It was found that both derivatives modulated the expression of the pathway-related genes that are important in inflammatory signaling, apoptosis, ATM/ATR, double-strand break repair, and the cell cycle. Furthermore, 2-CdA, K1-5d, and K2-4c significantly activated apoptosis in both cell lines. In summary, our data demonstrate that although both derivatives act as anti-inflammatory and apoptotic agents, inducing the accumulation of DNA strand breaks and activating the ultimate tumor suppressor p53 in T and B lymphocytes, the K1-5d derivative has shown more promising activities for further studies