ATR-IR and EPR spectroscopy for following the membrane restoration of isolated cortical synaptosomes in aluminium-induced Alzheimer's disease - Like rat model.

Synaptosomal membrane peroxidation and alteration in its biophysical properties are associated with Aluminium (Al) toxicity that may lead to cognitive dysfunction and Alzheimer's disease (AD) like pathogenesis. Here we investigated the therapeutic potential of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetyl cholinesterase inhibitor in treating Al induced AD-like in rat model. We utilized ATR-IR spectroscopy to follow the restoration in the damaged membrane structure of isolated rat cortical synaptosomes and its biophysical properties, electron paramagnetic resonance (EPR) spin trapping to follow NADPH oxidase activity (NOX), and EPR spin labelling in response to LS treatment after Al intoxication. We measured the concentration of Ca2+ ions in rat cortical tissue by inductively coupled plasma (ICP), the brain atrophy/curing and hydrocephalus by magnetic resonance imaging (MRI) besides light microscope histopathology. Our results revealed significant increase in synaptosomal membrane rgidification, order, lipid packing, reactive oxygen species (ROS) production and Ca2+ ion concentration as a result of Al intoxication. The dramatic increase in Ca2+ ion concentration detected in AD group associated with the increase in synaptic membrane polarity and EPR-detected order S-parameter suggest that release of synaptic vesicles into synaptic cleft might be hindered. LS treatment reversed these changes in synaptic membranes, and rescued an observed deficit in the exploratory behaviour of AD group. Our results also strongly suggest that the synaptosomal membrane phospholipids that underwent free radical attacks mediated by AlCl3, due to greater NOX activity, was prevented in the LS group. The results of ATR-IR and EPR spectroscopic techniques recommend LS as a promising therapeutic agent against synaptic membrane alterations opening a new window for AD drug developers.

Combination of Mesenchymal Stem Cells, Cartilage Pellet and Bioscaffold Supported Cartilage Regeneration of a Full Thickness Articular Surface Defect in Rabbits.

BACKGROUND: Mesenchymal stem cells (MSCs) and/or biological scaffolds have been used to regenerate articular cartilage with variable success. In the present study we evaluated cartilage regeneration using a combination of bone marrow (BM)-MSCs, HyalofastTM and/or native cartilage tissue following full thickness surgical cartilage defect in rabbits. METHODS: Full-thickness surgical ablation of the medial-tibial cartilage was performed in New Zealand white (NZW) rabbits. Control rabbits (Group-I) received no treatment; Animals in other groups were treated as follows. Group-II: BM-MSCs (1 × 106 cells) + HyalofastTM; Group-III: BMMSCs (1 × 106 cells) + cartilage pellet (CP); and Group-IV: BM-MSCs (1 × 106 cells) + HyalofastTM + CP. Animals were sacrificed at 12 weeks and cartilage regeneration analyzed using histopathology, International Cartilage Repair Society (ICRS-II) score, magnetic resonance observation of cartilage repair tissue (MOCART) score and biomechanical studies. RESULTS: Gross images showed good tissue repair (Groups IV > III > Group II) and histology demonstrated intact superficial layer, normal chondrocyte arrangement, tidemark and cartilage matrix staining (Groups III and IV) compared to the untreated control (Group I) respectively. ICRS-II score was 52.5, 65.0, 66 and 75% (Groups I-IV) and the MOCART score was 50.0, 73.75 and 76.25 (Groups II-IV) respectively. Biomechanical properties of the regenerated cartilage tissue in Group IV closed resembled that of a normal cartilage. CONCLUSION: HyalofastTM together with BM-MSCs and CP led to efficient cartilage regeneration following full thickness surgical ablation of tibial articular cartilage in vivo in rabbits. Presence of hyaluronic acid in the scaffold and native microenvironment cues probably facilitated differentiation and integration of BM-MSCs.

Brain MRI and CT findings in sickle cell disease patients from Western Saudi Arabia.

OBJECTIVE: To report the clinical and imaging findings in patients living in the Western Province of the Kingdom of Saudi Arabia where the Benin b-globin gene haplotype is prevalent. METHODS: Our study population consists of 36 sickle cell disease patients (17 males, 19 females; age range, 1.6-35.6 years; mean age, 19.4 years) with suspected cerebrovascular complications. Major clinical presentations were as follows: stroke symptoms or history of stroke in 13 (36%) patients, severe headache in 16 (44.4%), and seizures in 9 (25%). All patients underwent brain CT, or MRI study, or both, including diffusion imaging and magnetic resonance angiography. We conducted the study between August 2001 and June 2004 at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. RESULTS: Based on MRI, or CT, or both, we found cortical infarction in 30.6% (11/36) of patients. The frontoparietal temporal region was the most commonly involved part and occurred in 4 patients. We diagnosed small vessel disease in 38.9% (14/36) of patients, and involvement was bilateral in 9 patients. Small vessel disease involved deep white mater more than basal ganglia, and the caudate nucleus was the most commonly involved site in basal ganglia. We detected cerebral atrophy in 52.8% (19/36) of patients. An unusual finding was an epidural hematoma associated with skull bone infarctions and scalp edema that we successfully managed conservatively. We observed a widening of the diploic space of the skull in 10 patients. We saw adenoid hypertrophy in a significant number of patients (72% [26 of 36]). CONCLUSION: Sickle cell disease cerebrovascular complications are of major concern to the physician. Cerebral atrophy is the most common imaging finding followed by small vessel disease and then by cortical infarction. There was an increased incidence of adenoid hypertrophy.