Dragana Obradovic

Association of polymorphisms in CTLA-4, IL-1ra and IL-1β genes with multiple sclerosis in Serbian population

We have investigated separate as well as combined influence of IL-1beta TaqI, IL-1ra VNTR and CTLA-4 + 49 A/G polymorphisms on susceptibility, clinical course and progression of MS in 162 Serbian patients. We found significant independent relative risk for MS susceptibility in noncarriers of IL-1ra allele 2 (OR = 2.2, CI = 1.3-3.7, p = 0.003) and CTLA-4 + 49 AA genotype (OR = 2.0, CI = 1.2-3.5, p = 0.01) as well as their combined effect (OR = 4.4, CI = 2.0-9.7, p = 0.0003). Our result supports the significant and combined effect of IL-1ra VNTR and CTLA-4 polymorphisms on MS justifying the need for further haplotype analysis in different populations.

The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement

Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case–control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8–14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity.

Stem cells use in the treatment of neurologic disorders: Has the future already arrived?

Buducnost celijske terapije u lecenju neuroloskih bolesti je pocela. Ostaju važna pitanja na koja odgovor mogu dati samo dobro osmisljene međunarodne studije, a ticu se vrste celija, nacina njihovog umnožavanja i aplikacije, kao i optimalnog vremenskog okvira za ovakvu vrstu lecenja.

Fibrinogen kao faktor rizika za ishemijsku bolest srca

Mesto fibrinogena u razvoju ateroskleroze i arterijske tromboze je verovatno znacajno jer on ucestvuje i u procesu nastanka i rasta plaka modulise hemoreoloske osobine krvi, a cini i osnovu koaguluma tokom procesa tromboze. Koncentracija fibrinogena u krvi je dobar nezavisan prognosticki parametar za razvoj akutnog infarkta miokarda, kako kod zdravih odraslih osoba, tako i kod koronarnih bolesnika. Nivo fibrinogena u krvi je delimicno genetski determinisan, ali i brojni faktori spoljasnje sredine uticu na njegov nivo. Vrlo je bitan odnos između fibrinogena i nekih drugih važnih faktora rizika. Fibrinogen i holesterol imaju izgleda sinergisticki ucinak na razvoj akutnog koronarnog sindroma. Moguce je da je fibrinogen jedna od najznacajnijih spona između pusenja i koronarne bolesti. Veoma je mali broj lekova koji se mogu dugorocno primenjivati i smanjiti nivo fibrinogena u krvi, tako da za sada ne postoje klinicke studije o vrednosti ovakve terapije u lecenju i prevenciji akutnih koronarnih sindroma. Shodno tome sve dok se ne dokaže da se smanjenjem nivoa fibrinogena u krvi smanjuje rizik za ispoljavanje koronarne bolesti, njegova uloga kao faktora rizika ostaje nedovoljno definisana.

Urgent carotid stenting before cardiac surgery in a young male patient with acute ischemic stroke caused by aortic and carotid dissection

Introduction Acute aortic dissection (AD) is the most common life-threatening disorder affecting the aorta. Neurological symptoms are present in 17-40% of cases. The management of these patients is controversial. Case report We presented a 37-year-old man admitted for complaining of left-sided weak-ness. Symptoms appeared two hours before admission. The patient had no headache, neither thoracic pain. Neurological examination showed mild confusion, left-sided hemiplegia, National Institutes of Health Stroke Scale (NIHSS) score was 10. Ischemic stroke was suspected, brain multislice computed tomography (MSCT) and angiography were performed and right intrapetrous internal carotid artery dissection noted. Subsequent color Doppler ultrasound of the carotid arteries showed dissection of the right common carotid artery (CCA). The patient underwent thoracic and abdominal MSCT aortography which showed ascending aortic dissection from the aortic root, propagating in the brachiocephalic artery and the right CCA. Digital subtraction angiography was performed subsequently and two stents were successfully implanted in the brachiocephalic artery and the right CCA prior to cardiac surgery, only 6 hours after admission. The ascending aorta was reconstructed with graft interposition and the aortic valve re-suspended. The patient was hemodynamically stable and with no neurologic deficit after surgery. Unfortinately, at the operative day 6, mediastinitis developed and after intensive treatment the patients died 35 days after admission. Conclusion In young patients with suspected stroke and oscillatory neurological impairment urgent MSCT angiography of the brain and neck and/or Doppler sonography of the carotid and vertebral artery are mandatory to exclude carotid and aortic dissection. The prompt diagnosis permits urgent carotid stenting and cardiosurgery. To the best of our knowledge, this is the first published case of immediate carotid stenting in acute ischemic stroke after the diagnosis of carotid and aortic dissection and prior to cardiac surgery