Neuronal activity-dependent myelin repair after stroke.

Brain tissue undergoes substantial activity-dependent reorganisation after stroke due to neuronal plasticity, leading to partial functional recovery in patients. Concurrent myelin repair is crucial for proper neuronal network function and reorganisation. Myelin repair after stroke might occur as myelin plasticity or as remyelination through the recruitment and differentiation of oligodendrocyte precursor cells (OPCs), which become myelin-forming oligodendrocytes (OLs). These two processes might share a similar guiding mechanism, which is postulated to depend on neuronal activity and glutamate signaling to OPCs. However, with ageing, the ability of OPCs to differentiate into myelinating OLs decreases due to changes in their ion channel and neurotransmitter receptor expression profile, rendering them less sensitive to neuronal activity. Because of their unique ability to replace damaged OLs, OPCs represent a potential therapeutic target for myelin repair in the context of stroke

Medium- and high-cell-density production of Adeno-Associated virus serotype 6 and the mitigation of cell density effect via medium supplementation

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A Matter of State: Diversity in Oligodendrocyte Lineage Cells.

Oligodendrocyte precursor cells (OPCs) give rise to oligodendrocytes which myelinate axons in the central nervous system. Although classically thought to be a homogeneous population, OPCs are reported to have different developmental origins and display regional and temporal diversity in their transcriptome, response to growth factors, and physiological properties. Similarly, evidence is accumulating that myelinating oligodendrocytes display transcriptional heterogeneity. Analyzing this reported heterogeneity suggests that OPCs, and perhaps also myelinating oligodendrocytes, may exist in different functional cell states. Here, we review the evidence indicating that OPCs and oligodendrocytes are diverse, and we discuss the implications of functional OPC states for myelination in the adult brain and for myelin repair

Medical history among Bulgarian patients with fever of unknown origin and low-grade fever

Въведение: Персистиращият фебрилитет с неизвестен произход е предизвикателство пред медицинската общност. Целта на тази статияе да се представят анамнестичните данни при български пациенти с неясно фебрилно състояние (НФС) и субфебрилна температура.Материали и методи: За периода от 01.02.2012г. до 01.08.2015г. в Клиниката по инфекциозни болести към ВМА-София се проведе проспективно проучване на пациенти с НФС и субфебрилитет. Изследвани бяха общо 117 пациенти, от тях с НФС - 88 човека, със субфебрилитет 29 човека. В настоящата работа са използвани следните методи: библиографски метод, метод на сравнението и клинични методи.Резултати: Основните анамнестични данни, имащи принос към поставянето на окончателната диагноза при всички проучени пациенти, са следните - умора, изпотяване, втрисане, главоболие и артралгия.Заключение: Анамнезата е от съществено значение за крайния успех в диагностиката на фебрилитета с неизвестен произход. Тя се явява първа стъпка в диагностичния алгоритъм при НФС.Introduction: The persisting fever of indeterminate genesis is a challenging for the medical society. The aim of this paper was to present the medical history of Bulgarian patients with fever of unknown origin (FUO) and low-grade fever (non-FUO).Materials and methods: A prospective study of patients with FUO and non-FUO was done at the Department of Infectious Diseases, Military Medical Academy (Sofia, BG) for the period: 1st February 2012 - 1st August 2015. A population of 117 patients were analyzed, 88 - FUO, 29 - non-FUO. The following methods were applied: literature review, a method of comparison and clinical evaluation.Results: The main historical data which are leading to the final diagnosis in the whole analyzed group were: fatigue, sweats, chills, headache and arthralgia.Conclusion: The medical history is a basic key in the diagnostic pathway to the final diagnosis in case of fever of undetermined origin. This is the first step in the diagnostic algorithm

Infekcija virusom Zapadnog Nila s neurološkim poremećajima: prikaz slučaja i kratak pregled stanja u Bugarskoj

A case of a 66-year-old man with West Nile neuroinvassive disease manifested with fever, weakness, fa-tigue, consciousness disorders and underlying diabetes mellitus type 2 and cardiovascular diseases is pre-sented. Laboratory data showed elevated erythrocyte sedimentation rate and fibrinogen. Serological tests revealed West Nile virus specific antibodies of class IgM and IgG in serum. West Nile virus RNA was de-tected in urine sample. Supportive therapy was applied.Prikazuje se slučaj 66-godišnjeg bolesnika s neuroinvazivnom bolešću Zapadnog Nila koja se manifestirala grozni-com, umorom, poremećajem svijesti uz osnovnu bolest dijabetesa tipa 2 i kardiovaskularnom bolešću. Laboratorij-ski podaci pokazali su povišenu sedimentaciju i fibrinogen. Serološki testovi utvrdili su protutijela specifična za virus Zapadnog Nila klase IgM i IgG u serumu. Virusna RNA otkrivena je u uzorku mokraće. Primijenjena je suportivna terapija

Transient transfection of serum-free suspension HEK 293 cell culture for efficient production of human rFVIII

Abstract\ud \ud \ud \ud Background\ud \ud Hemophilia A is a bleeding disorder caused by deficiency in coagulation factor VIII. Recombinant factor VIII (rFVIII) is an alternative to plasma-derived FVIII for the treatment of hemophilia A. However, commercial manufacturing of rFVIII products is inefficient and costly and is associated to high prices and product shortage, even in economically privileged countries. This situation may be solved by adopting more efficient production methods. Here, we evaluated the potential of transient transfection in producing rFVIII in serum-free suspension HEK 293 cell cultures and investigated the effects of different DNA concentration (0.4, 0.6 and 0.8 μg/106 cells) and repeated transfections done at 34° and 37°C.\ud \ud \ud \ud Results\ud \ud We observed a decrease in cell growth when high DNA concentrations were used, but no significant differences in transfection efficiency and in the biological activity of the rFVIII were noticed. The best condition for rFVIII production was obtained with repeated transfections at 34°C using 0.4 μg DNA/106 cells through which almost 50 IU of active rFVIII was produced six days post-transfection.\ud \ud \ud \ud Conclusion\ud \ud Serum-free suspension transient transfection is thus a viable option for high-yield-rFVIII production. Work is in progress to further optimize the process and validate its scalability.The authors would like to acknowledge FAPESP (2008/51505-7) and FINEP (01.07.0652.00) for financial support