A pulsed NMR study of lipids,bound water and sodium ions in macroscopically-oriented lecithin/water lyotropic liquid crystal model membrane systems

The temperature and orientation dependence of pulsed NMR ‘free induction decay’ signals have been studied in detail for lipid bilayers macroscopically-oriented between glass slides. Results for the lipid molecules (¹H, ³¹P), bound water (²H₂O) and ions dissolved in the aqueous phase (²³Na) are presented. Bilayers of egg-lecithin, dimyristoyl lecithin and potassium oleate have been investigated. In the liquid crystal phase all the signals, including those from bound water and ions exhibit a |3 cos²? ? 1| dependence on orientation of the bilayer normal to the magnetic field. In the case of DML samples, some orientation dependence of both ¹H and ²H signals persists in the gel phase, indicating that the lipid molecules retain a degree of reorientational freedom about their long axes in this phase. At the gel-liquid crystal transition the ²H quadrupole spittings undergo a discontinuous change. Results are interpreted in terms of a model in which water molecules are bound to individual lipid head groups and reorient with them, while sodium ions are located in the aqueous channel between bilayers.     

Comparative effects of ethanol, n-propranol and isopropanol on lipid disposal by rat liver.

Besides ethanol, other aliphatic alcohols such as n-propanol and isopropanol induce a triacylglycerol (TAG) accumulation in the liver. To determine whether a common mechanism is responsible for the effects of these three alcohols on hepatic lipid metabolism, each was administered by gastric tube to female Wistar rats at the dose of 50 mmol/kg body wt. Whichever alcohol was administered, the hepatic triacylglycerol accumulation was found to be related to the duration of elevated blood alcohol concentration. After administration of n-propanol or isopropanol, the liver [14C]palmitate uptake was increased whereas hepatic palmitate oxidation to 14CO2 was impaired and palmitate esterification into TAG enhanced; these perturbations were however more discrete than after ethanol administration. In contrast to ethanol and n-propanol which, at the dose presently used, increase precursor incorporation into blood TAG, isopropanol inhibits this incorporation. Interference with the process of very low density lipoprotein (VLDL) synthesis and/or secretion, which appears only at a late stage of isopropanol intoxication, is probably responsible for the intensity and duration of the fatty liver observed after administration of this alcohol.     

Magnesium (and trace substance) deficiencies in the pathogenesis of cancer

Except for a few experimental models of magnesium (Mg)-deficiency-induced neoplasms, less attention has been paid in the past quarter century in the Western world to this macromineral than to the trace elements; e.g., selenium (Se) and zinc (Zn), and to vitamins, deficiencies of which are each considered probable factors in oncogenesis. Although early epidemiologic studies showed an inverse correlation between the amount of Mg in soil and water and the incidence of (gastric) cancer, and several animal studies supported the premise that Mg has a prophylactic effect against induction of cancer, other studies showed that Mg supplementation increased the growth of established experimental tumors. Thus, enthusiasm for this approach subsided. The early epidemiologic findings have since been confirmed, and there have been studies demonstrating the importance of Mg in maintaining immunocompetence, and others indicating that immunodeficiencies increase susceptibility to the development of cancer. Evidence has now accrued that indicates that Mg deficiency increases susceptibility to chemical oncogens. The abnormal metabolism of tryptophan (yielding a carcinogenic metabolite) that indicates functional or absolute pyridoxine deficiency is an indirect clue to Mg deficiency. Vitamin B₆-activated enzymes require Mg as a cofactor. However, the early warnings against the use of Mg as part of an antineoplastic program against established cancer were justified, since rapidly metabolizing cells (such as cancers) are dependent on Mg. There are similarities between experiences with Mg and with Se and Zn. All three are required for normal metabolism; Se also protects against free radicals in the environment. Mg and Zn have increased established tumor growth, and their depletion has been applied to antineoplastic programs, with risks comparable to those of using antimetabolic agents.     

Studies on the binary and ternary complexes formed by a neurospora glutamate dehydrogenase and its substrates

The NADP⁺ specific glutamate dehydrogenase from wild-type $\text{Neurospora crassa}$ forms a stable binary complex with NADPH. This can combine with L-glutamate, α-ketoglutarate or the substrate analogue D-glutamate to form ternary complexes which can be distinguished by their different fluorescence properties. The affinity of the enzyme for NADPH diminishes with increases in pH or ionic strength of the solution. Experimental data obtained using modified glutamate dehydrogenases from mutant strains of $\text{N. crassa}$ suggest that the reduced-coenzyme binding sites observed fluorimetrically are the same as those observed by enzyme kinetics.     

Free Radical Enhancer Xenobiotic is an Inducer of Cataract in Rabbit

Free radical enhancers, diquat, paraquat, plumbagin and juglone were used to study the oxy radical-induced damage to the rabbit lens in vitro and in vivo. Each compound caused a 6–8 fold increase in malondialdehyde (MDA) and a 30–55% decrease in reduced glutathione of the lens in vim. These peroxidative and oxidative changes were potentiated in the presence of 100% 0., abolished by N, and prevented by desferal-Mn (III) (DF-Mn) or liposomal superoxide dismutase (LSOD) indicating the involvement of O₂^?.

Diquat injected intravitreally as a single dose (300nmole in 30μl of isotonic saline) in the right eye of a 5-wk-old Dutch belted rabbit, induced early cataract after 24–72h. The lens of the contralateral control eye injected with isotonic saline had no change. In the right eye, O₂,^? and OH -productions were significantly (P < 0.01) higher; O₂-, was about 16 fold higher in the aqueous humor and vitreous humor, and 5 fold in the lens and retina, and OH. was 35 fold higher in the aqueous humor, 2 fold in vitreous humor and 5 fold in the lens and retina as compared to the respective tissues of the control eye. Enhanced lipid peroxidation in the lens was apparent from the higher levels of MDA and formation of aminophospholipid-MDA Schiff-base conjugates.

We propose that cyclic oxidation-reduction of xenobiotics coupled to the endogenous redox systems in the eye, could generate oxy radicals in excessive amounts, triggering cataractogcnesis.     

Transient Iron-Overload with Bleomycin-Detectable Iron Present During Cardiopulmonary Bypass Surgery

Extracorporeal circulation of blood during cardiopulmonary bypass surgery exposes cells to non-physiological surfaces and shear stress which can activate several regulatory cascades, and neutrophils to release superoxide and hydrogen peroxide. Shear stresses generated by pumps and suction systems cause lysis of red blood cells and the release of haemoglobin. Together the release of reactive forms of oxygen and haemoglobin can lead to the appearance of low molecular mass chelatable iron (bleomycin-detectable iron). All patients undergoing open heart surgery appear to release iron to plasma transferrin, increasing its iron saturation. In 13% of patients, however, the transferrin became fully iron-saturated, and by the end of open-heart surgery we could detect bleomycin-chelatable iron in the plasma. Saturation of transferrin with iron eliminates its iron-binding antioxidant properties, which can result in a stimulation of iron-dependent radical damage to selected detector molecules.