Does dietary tocopherol level affect fatty acid metabolism in fish?

Fish are a rich source of the n-3 polyunsaturated fatty acids (PUFA), particularly the highly unsaturated fatty acids (HUFA), eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic (DHA; 22:6n-3) acids, which are vital constituents for cell membrane structure and function, but which are also highly susceptible to attack by oxygen and other organic radicals. Resultant damage to PUFA in membrane phospholipids can have serious consequences for cell membrane structure and function, with potential pathological effects on cells and tissues. Physiological antioxidant protection involves both endogenous components, such as free radical scavenging enzymes, and exogenous dietary micronutrients including tocopherols and tocotrienols, the vitamin E-type compounds, widely regarded as the primary lipid soluble antioxidants. The antioxidant activities of tocopherols are imparted by their ability to donate their phenolic hydrogen atoms to lipid (fatty acid) free radicals resulting in the stabilisation of the latter and the termination of the lipid peroxidation chain reaction. However, tocopherols can also prevent PUFA peroxidation by acting as quenchers of singlet oxygen. Recent studies on marine fish have shown correlations between dietary and tissue PUFA/tocopherol ratios and incidence of lipid peroxidation as indicated by the levels of TBARS and isoprostanes. These studies also showed that feeding diets containing oxidised oil significantly affected the activities of liver antioxidant defence enzymes and that dietary tocopherol partially attenuated these effects. However, there is evidence that dietary tocopherols can affect fatty acid metabolism in other ways. An increase in membrane PUFA was observed in rats deficient in vitamin E. This was suggested to be due to over production of PUFA arising from increased activity of the desaturation/elongation mechanisms responsible for the synthesis of PUFA. Consistent with this, increased desaturation of 18:3n-3 and 20:5n-3 in hepatocytes from salmon fed diets deficient in tocopherol and/or astaxanthin has been observed. Although the mechanism is unclear, tocopherols may influence biosynthesis of n-3PUFA through alteration of cellular oxidation potential or “peroxide tone”

Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells

Stroke in sickle cell anemia: New concepts in diagnosis and management

Stroke is a devastating and potentially fatal complication of sickle cell disease. The highest incidence of cerebrovascular disease is in the first 10 years and especially between 2 to 5 years. Two types of stroke occur in these patients – infarctive and hemorrhagic strokes. While infarctive strokes occur frequently in children, hemorrhagic strokes occur mostly in adults. Associated risk factors include: history of transient ischemic attacks, association of acute chest syndrome, severe anemia, a high leukocyte count and a genetic susceptibility. In the presence of stroke, the main investigations are computed tomography and magnetic resonance imaging. Primary prevention is the main axis of management. This consists of transcranial Doppler ultrasonography screening in sicklers as from 2 years of age every 6 months, and patients with abnormal velocities of or greater than 200cm/seconds should receive chronic transfusion therapy every 3 – 4 weeks. The decision to initiate transfusion should be based on careful consideration of the risks and benefits. This with the aim of averting the inherent motor and neuropsychogical impairments from stroke.L'accident vasculaire cérébral (AVC) chez le drépanocytaire est une complication grave greffée d'une mortalité élevée.L'incidence la plus élevée est dans la première décennie de la vie surtout entre 2 et 5 ans. Il existe deux types d'AVC chez le drépanocytaire – ischémique et hémorragique. Les accidents ischémiques surviennent surtout chez les enfants, et les accidents hémorragiques surtout chez les adultes. Les facteurs prédisposants sont : l'antécédent d'accident ischémique transitoire, le syndrome thoracique aiguë, l'anémie sévère, la leucocytose et une susceptibilité génétique. En présence d'AVC, les principaux examens sont : le scanner cérébral, et l'imagerie par résonance magnétique. La prévention primaire reste le principal axe du traitement. Ceci consiste à pratiquer un Doppler transcrânien chez les drépanocytaires dès l'âge de 2 ans et tous les 6 mois et les patients ayant des vitesses moyennes des artères du polygone de Willis supérieur ou égale à 200 cm/seconde bénéficieront d'un programme de transfusion périodique toutes les 3-4 semaines. La décision d'initier la transfusion ne doit être prise qu'après avoir évalué les risques et bénéfices des transfusions. Cette prise en charge permet de prévenir les séquelles motrices et neuropsychiques liées à cette affection. Keywords: Stroke - Sickle cell anemia - Risk factors - Clinical presentation - Diagnosis - Management Clinics in Mother and Child Health Vol. 3(2) 2006: pp. 585-59