N-Acetylcysteine Nanocarriers Protect against Oxidative Stress in a Cellular Model of Parkinson's Disease.

Oxidative stress is a key mediator in the development and progression of Parkinson's disease (PD). The antioxidant n-acetylcysteine (NAC) has generated interest as a disease-modifying therapy for PD but is limited due to poor bioavailability, a short half-life, and limited access to the brain. The aim of this study was to formulate and utilise mitochondria-targeted nanocarriers for delivery of NAC alone and in combination with the iron chelator deferoxamine (DFO), and assess their ability to protect against oxidative stress in a cellular rotenone PD model. Pluronic F68 (P68) and dequalinium (DQA) nanocarriers were prepared by a modified thin-film hydration method. An MTT assay assessed cell viability and iron status was measured using a ferrozine assay and ferritin immunoassay. For oxidative stress, a modified cellular antioxidant activity assay and the thiobarbituric acid-reactive substances assay and mitochondrial hydroxyl assay were utilised. Overall, this study demonstrates, for the first time, successful formulation of NAC and NAC + DFO into P68 + DQA nanocarriers for neuronal delivery. The results indicate that NAC and NAC + DFO nanocarriers have the potential characteristics to access the brain and that 1000 μM P68 + DQA NAC exhibited the strongest ability to protect against reduced cell viability ( = 0.0001), increased iron ( = 0.0033) and oxidative stress ( ≤ 0.0003). These NAC nanocarriers therefore demonstrate significant potential to be transitioned for further preclinical testing for PD

Compartmentalized megakaryocyte death generates functional platelets committed to caspase-independent death

Caspase-directed apoptosis usually fragments cells, releasing nonfunctional, prothrombogenic, membrane-bound apoptotic bodies marked for rapid engulfment by macrophages. Blood platelets are functional anucleate cells generated by specialized fragmentation of their progenitors, megakaryocytes (MKs), but committed to a constitutive caspase-independent death. Constitutive formation of the proplatelet-bearing MK was recently reported to be caspase-dependent, apparently involving mitochondrial release of cytochrome c, a known pro-apoptogenic factor. We extend those studies and report that activation of caspases in MKs, either constitutively or after Fas ligation, yields platelets that are functionally responsive and evade immediate phagocytic clearance, and retain mitochondrial transmembrane potential until constitutive platelet death ensues. Furthermore, the exclusion from the platelet progeny of caspase-9 present in the progenitor accounts for failure of mitochondrial release of cytochrome c to activate caspase-3 during platelet death. Thus, progenitor cell death by apoptosis can result in birth of multiple functional anucleate daughter cells

Ar didelio meistriškumo sportas skatina medicinos pažangą?

In an era where the discovery and development of new medicine have hit its peak, areas of study that generate new thinking and related opportunity for medicine development are of great value. Society requires new medicine as an expanding ageing population in the developed world and the emergence of Western world diseases in the developing world place pressure on our global healthcare capability. Here we explore the possible meaning of elite sport to global, cutting edge medical advance. Why the elite sports industry might drive such advance? We believe that there are two broad areas to do this: 1. Discovery of bioactive molecules with medicine development potential based upon the exploration of the molecular basis of responses to exercise and physical activity and area of research endeavor known as mechanotransduction. This area of study has revealed the incredible potential for a range of naturally occurring molecules to maintain musculoskeletal health and has identified some of the key cell types responsible for orchestrating the beneficial responses. In particular, the bone resident osteocyte has been transformed from a little studies quiescent cell type into the foreman in charge of bone shape, size, and strength and also distant kidney function. 2. The clinical need generated by sport injuries in the elite competing population. Injury in this professional group has greater meaning then in the amateur sports person in terms of both earnings and career progression. The generation of novel medicine and therapies is of great value and includes the emerging clinical specialty of regenerative medicine. This specialty includes the use of cell-based therapies and is emerging fast. At its best, a cellbased therapy will not just treat a clinical condition; rather, it will cure it. Instead of requiring multiple doses over extended periods to control a clinical condition, one dose will cure the condition through the establishment of live cells in the tissues of need. The future holds medical promise and a little acknowledged role that elite sport plays important role in the realization of that promise might well represent a legitimate area for clinical therapy discovery.Šiame medicinos pažangos ir atradimų proveržio amžiuje ypač didelę vertę turi naują požiūrį skatinantys tyrimai medicinos srityje. Daugėjant vyresnio amžiaus žmonių išsivysčiusiose šalyse, o besivystančiose šalyse vis labiau plintant Vakarų šalims būdingoms ligoms, kyla poreikis naujų medicinos atradimų, kurie savo ruožtu skatina ieškoti globalių sprendimų sveikatos priežiūros srityje. Šiame straipsnyje tirtas didelio meistriškumo sporto galimas poveikis globaliai, toli pažengusiai medicinai ir nagrinėtos jo priežastys. Galima būtų išskirti dvi sritis, kuriose vyksta minėti procesai: 1. Medicininį potencialą turinčių bioaktyvių molekulių atradimas, grindžiamas molekuliniu atsaku į judėjimą bei fizinį aktyvumą, ir tyrimų sritis, žinoma kaip mechaninė transdukcija. Šioje mokslinėje srityje atskleista daug informacijos apie natūralias molekules, palaikančias gerą griaučių raumenų būklę. Taip pat nustatyti keli už teigiamų atsakų suaktyvinimą atsakingi ląstelių tipai, būtent kaulinio audinio ląstelė – osteocitas iš mažai tirtos, ramios būsenos ląstelės tapo aktyvia ląstele, atsakinga už kaulo formą, dydį ir stiprumą, taip pat iš dalies ir už inkstų funkciją. 2. Gydymo poreikis, atsiradęs dėl sporto traumų didelio meistriškumo sporte. Traumos sportininkams profesionalams turi didesnę reikšmę nei asmenims, vadinamiems sportuotojais, – tiek karjeros, tiek atlyginimo prasme. Naujų vaistų ir gydymo būdų atradimai yra ypač vertingi: atsirado nauja klinikinė specialybė – regeneracinė medicina. Šioje sparčiai besivystančioje šakoje taikomas vertingas, ląstelės tyrimais paremtas gydymas: užuot ilgą laiką klinikinei paciento būklei kontroliuoti vartojus didelėmis dozėmis vaistus, negalavimas gali būti pagydytas į atitinkamus audinius įkeldinus reikiamas gyvas ląsteles. Dėl išvardytų priežasčių didelio meistriškumo sportas gali paskatinti medicinos vystymąsi darant naujus atradimus klinikinės terapijos srityje

3-D printouts of the tracheobronchial tree generated from CT DICOM files as an aid to planning future interventional management in a case of extensive tracheobronchial chondromalacia caused by advanced relapsing polychondritis

This report concerns a 67 year old male patient with known advanced relapsing polychondritis complicated by tracheobronchial chondromalacia who is increasingly symptomatic and therapeutic options such as tracheostomy and stenting procedures are being considered. The DICOM files from the patient’s dynamic chest CT in its inspiratory and expiratory phases were used to generate stereolithography (STL) files and hence print out 3-D models of the patient’s trachea and central airways. The 4 full-sized models allowed better understanding of the extent and location of any stenosis or malacic change and should aid any planned future stenting procedures. The future possibility of using the models as scaffolding to generate a new cartilaginous upper airway using regenerative medical techniques is also discussed

Bone tissue formation from human embryonic stem cells in vivo

Although the use of embryonic stem cells in the assisted repair of musculoskeletal tissues holds promise, a direct comparison of this cell source with adult marrow-derived stem cells has not been undertaken. Here we have compared the osteogenic differentiation potential of human embryonic stem cells (hESC) with human adult-derived stem cells in vivo. hESC lines H7, H9, the HEF-1 mesenchymal-like, telomerized H1 derivative, the human embryonic kidney epithelial cell line HEK293 (negative control), and adult human mesenchymal stem cells (hMSC) were either used untreated or treated with osteogenic factors for 4 days prior to injection into diffusion chambers and implantation into nude mice. After 11 weeks in vivo chambers were removed, frozen, and analyzed for evidence of bone, cartilage, and adipose tissue formation. All hESCs, when pretreated with osteogenic (OS) factors gave rise exclusively to bone in the chambers. In contrast, untreated hESCs (H9) formed both bone and cartilage in vivo. Untreated hMSCs did not give rise to bone, cartilage, or adipose tissue in vivo, while pretreatment with OS factors engendered both bone and adipose tissue. These data demonstrate that hESCs exposed to OS factors in vitro undergo directed differentiation toward the osteogenic lineage in vivo in a similar fashion to that produced by hMSCs. These findings support the potential future use of hESC-derived cells in regenerative medicine applications