Pathophysiology, Clinical, and Therapeutic Aspects of Narcolepsy

Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. There have been advances in the understanding of the pathogenesis of narcolepsy. It has a negative effect on the quality of life and can restrict the patients from certain careers and activities. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioral modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Some novel modalities are being examined to expand options for treatment. In this review, the pathophysiological, clinical, and pharmacotherapeutic aspects of narcolepsy are discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000): 271-283

Çok gövdeli sistemlerde hareket analizi

Çok göovdeli sistemlerin hareket analizi son yıllarda önemli bir araştırma konusu haline gelmiştir. Bunun sebebi performans analizi, otomatik güvenlik ve izleme sistemlerinin gerçeklenmesi, gerçekçi insan-makine arayüzlerinin oluşturulması, içerik tabanlı imge depolanması ve erişimi gibi motive edici uygulama alanlarının varlığıdır. Bu alanda çok sayıda çalışma yayınlanmış olsa da bu araştırmanın henüz geliştirilebilecek yönleri vardır. Bu çalışmada, çok gövdeli bir sistemin hareketini, sistemi her biri birer robotik kol şeklindeki çok sayıda alt sisteme ayrıştırarak incelemeyi öneriyoruz. Çok gövdeli bir sistemin hareketini tanımak için her bir robotik kolun eklemlerinden gelecek algılayıcı bilgisini, yani eklem açılarını kullanıyoruz. Önerilen yöntem herbir ayrıştırılmış parçanın periyodik hareketini analiz etmek için eklem açılarının birbirine göre çizdirilmesiyle elde edilen imza eğrilerini kullanmaktadır. Akt¨or ayırt etme ve aksaklık tesbiti örnekleri sunulmuş ve önerilen yöntem benzetimlerle doğrulanmıştır

Novel beta-lactam substituted benzenesulfonamides: in vitro enzyme inhibition, cytotoxic activity and in silico interactions

ABSTRACT In this study, a library of twelve beta-lactam-substituted benzenesulfonamides (5a–l) was synthesized using the tail-approach method. The compounds were characterized using IR, 1 H NMR, 13C NMR and elemental analysis techniques. These newly synthesized compounds were tested for their ability to inhibit the activity of two carbonic anhydrases (hCA) isoforms, I and II, and acetylcholinesterase (AChE) in vitro. The results showed that the synthesized compounds were potent inhibitors of hCA I, with KI s in the low nanomolar range (66.60–278.40 nM) than the reference drug acetazolamide (AAZ), which had a KI of 439.17 nM. The hCA II was potently inhibited by compounds 5a, 5d–g and 5l, with KI s of 69.56, 39.64, 79.63, 74.76, 78.93 and 74.94 nM, respectively (AAZ, KI of 98.28 nM). Notably, compound 5a selectively inhibited hCA II with a selectivity of > 4-fold over hCA I. In terms of inhibition of AChE, the synthesized compounds had KI s ranging from 30.95 to 154.50 nM, compared to the reference drug tacrine, which had a KI of 159.61 nM. Compounds 5f, 5h and 5l were also evaluated for their ability to inhibit the MCF-7 cancer cell line proliferation and were found to have promising anticancer activity, more potent than 5-fluorouracil and cisplatin. Molecular docking studies suggested that the sulfonamide moiety of these compounds fits snugly into the active sites of hCAs and interacts with the Zn2þ ion. Furthermore, molecular dynamics simulations were performed for 200 ns to assess the stability and dynamics of each enzyme-ligand complex. The acceptability of the compounds based on Lipinski’s and Jorgensen’s rules was also estimated from the ADME/T results. These results indicate that the synthesized molecules have the potential to be developed into effective and safe inhibitors of hCAs and AChE and could be lead agents

Contamination of Low Frictional Elastomeric Ligatures by Streptococcus mutans: A Prospective RT-PCR and AFM Study

Objective: To compare Streptococcus mutans colonization between low-friction elastomeric ligatures and to correlate microbial colonization levels with the surface roughness status.Methods: The study included 160 premolars of 10 patients. During the study period, which consisted of 4 sessions each lasting 4 weeks, the ligature types Slide™ Low-Friction Ligature (Leone, Firenze, Italy), Tough-O Energy™ (Rocky Mountain Orthodontics, Denver, USA), and Sili Ties™ (Dentsply Sirona, Surrey KT13 0NY, UK), and steel ligatures (American Orthodontics, Sheboygan, USA) as a control, were fixed to the premolar teeth by clockwise rotation among the jaw quadrants. The plaque index (PI) and gingival index (GI) were obtained before bonding (T0), 6 weeks after bonding (T1), and subsequently every 4 weeks (T2, T3, T4). Presence of S. mutans was analyzed by real-time polymerase chain reaction at T1, T2, T3, T4. Surface roughness was evaluated with Atomic Force Microscopy (AFM) before ligation (Ra0) and after (Ra1) ligation. The paired t-test, ANOVA, repeated measures of ANOVA, and the Kruskal–Wallis test were used for the statistical analysis.Results: S. mutans colonization was significantly higher on the Slide group (P .05).Conclusion:S. mutans colonization showed variations in low-friction elastomeric ligatures independent of surface roughness. Ringshaped low-friction elastomeric ligatures were not different from the steel ligature in terms of S. mutans colonization

Plasmapheresis in a Patient With "Refractory" Urticarial Vasculitis

Immune complexes are found in the circulation of 30%-75% of patients with urticarial vasculitis and much evidence supports the role of these immune complexes in the pathogenesis of urticarial vasculitis. Plasmapheresis is effective for removing these immune complexes; however, there are few reports on the use of plasmapheresis in the treatment of urticarial vasculitis. We describe a case of "refractory" urticarial vasculitis in which the symptoms improved after plasmapheresis treatment. We suggest that plasmapheresis be considered as an option in patients with severe or treatment-resistant urticarial vasculitis

Hydrogel Implant Causing Lumbar Radiculopathy: A Case Report

Objective: One of the new treatment methods for lumbar degenerative disc disease is percutaneous application of a hydrogel implant into the intervertebral disc. The aim of this method is to increase the disc height, to widen the neural foramen, and to decrease discogenic pain and leg pain caused by root compression. However, there may be serious complications related to intervertebral hydrogel implants that have been increasingly used during the last few years because of their minimally-invasive nature. A case with lumbar root compression due to hydrogel implant is being reported.Case Report: A 61-year-old male was admitted with severe left leg pain due to compression of the left L5 root by a hydrogel implant that had been percutaneously introduced into the L4-5 disc level 6 months ago. On magnetic resonance imaging, a lesion compressing the left L5 root at the L4-5 disc level and mimicking a disc herniation was seen. It was hypointense on T1-weighted and hyperintense on T2-weighted sections. The implant was removed by an open surgery.Conclusion: An intervertebral hydrogel implant swells up by absorbing water from adjacent tissues. Actually, this is the main mechanism of action by which it provides an increase of disc height. However, if it swells up excessively, it may spill over through the spinal canal and thus cause root or dural sac compression and neurological compromise