Impact on energy metabolism of quantitative and functional cyclosporine-induced damage of kidney mitochondria

In this study we have measured, under experimental conditions which maintained efficient coupling, respiratory intensity, respiratory control, oxidative phosphorylation capacity and protonmotive force. Succinate cytochrome-c reductase and cytochrome-c oxidase activities were also studied. These investigations were carried out using kidney mitochondria from cyclosporine-treated rats (in vivo studies) and from untreated rats in the presence of cyclosporine (in vitro studies). Inhibition of respiratory intensity by cyclosporine did not exceed 21.1% in vitro and 15.9% in vivo. Since there was no in vitro inhibition of succinate cytochrome-c reductase and cytochrome-c oxidase activities, the slowing of electron flow observed can be interpreted as a consequence of an effect produced by cyclosporine between cytochromes b and c₁. Cyclosporine had no effect on respiratory control either in vitro or in vivo. Statistically significant inhibition of the oxidative phosphorylation was observed both in vitro (6.6%) and in vivo (12.1%). Moreover, cyclosporine did not induce any change of membrane potential either in vivo or in vitro. Our findings show that cyclosporine is neither a protonophore, nor a potassium ionophore. In cyclosporine-treated rats we noticed a decrease of protein in subcellular fraction, including the mitochondrial fraction. The role of the inhibition respiratory characteristics by cyclosporine in nephrotoxicity in vivo must take account of these two parameters: inhibition of the respiratory characteristics measured in vitro and diminution of mitochondrial protein in cyclosporine-treated rats.     

Opposing effects of strychnine and brucine on the germination and growth of lettuce seeds

Strychnine and brucine, two related alkaloids that occur in plants belonging to theStrychnos species, were shown to have opposing effects on the elongation of the radicle of lettuce seeds. Strychnine was found to be inhibitory, whereas brucine was found to be stimulating to radicle elongation. Alkaloids, generally, are more commonly known for their inhibitory effects on plant growth rather than on their stimulating effects.     

Role of inositol trisphosphate as a second messenger in signal transduction processes: An essay

This essay attempts to summarize some of the best evidence for the role of inositol trisphosphate as a second messenger in signal transduction processes. The following aspects are addressed in the essay: (a) The synthesis of inositol trisphosphate and other inositol lipids, (b) Receptor-phosphatidylinositol bisphosphate phospholipase C coupling and the N-ras protooncogene, (c) Inositol trisphosphate and intracellular calcium, (d) Cell growth and oncogenes, (e) Receptors linked to the phosphatidylinositol cycle, (f) Phototransduction and (g) Interactions between inositol trisphosphate and other second messengers.Abbreviations Cyclic AMP Adenosine 3,5-cyclic monophosphate - Cyclic GMP Guanosine 3,5-cyclic monophosphate - DG sn, 1,2-Diacylglycerol - EGF Epidermal growth factor - GDP Guanosine diphosphate - GTP Guanosine triphosphate - IP Inositol 1-monophosphate - IP₂ Inositol 1,4-diphosphate - IP₃ Inositol 1,4,5-trisphosphate - PA Phosphatidic acid - PDGF Platelet-derived growth factor - PI Phosphatidylinositol - PIP Phosphatidylinositol 4-monophosphate - PIP₂ Phosphatidylinositol 4,5-bisphosphate - PIP₃ Phosphatidylinositol 3,4,5-trisphosphate - PLC Phospholipase C     

Pterygodermatites variabilis n. sp. (Nematoda: Rictularioidea) from the Indian gerbils of Pakistan

Pterygodermatites variabilis n. sp. (Nematoda: Rictulalarioidea) from the Indian gerbils Tatera indica collected from Sind and Baluchistan Provinces of Pakistan is described and compared with closely related species of the genus recovered from small mammalian hosts. The new species is characterised by a combination of the following characters: it possesses a regular crown of 26 and 14–38 denticles in male and female specimens respectively, 40–47 pairs of pre-vulvar spines, and a variable position of the vulva in specimens collected from different localities: it also differs in the size of the spicules and gubernaculum.     

Absence of a unique relationship between active transport of lactose and protonmotive force in E. coli

The relationship between active transport of lactose via the lactose permease and the protonmotive force has been determined in E. coli cells using either the respiratory chain inhibitor cyanide or protonophores to decrease the protonmotive force progressively. In contradiction with the prediction of the delocalized chemiosmotic theory, two different relationships were obtained depending on the method used.     

2-Bromoethyl glycosides in glycoside synthesis: preparation of glycoproteins containing alpha-L-Fuc-(1----2)-D-Gal and beta-D-Gal-(1----4)-D-GlcNAc

The applicability of 2-bromoethyl glycosides in carbohydrate synthesis is demonstrated by the synthesis of glycosides of alpha-L-Fuc-(1----2)-D-Gal and beta-D-Gal-(1----4)-D-GlcNAc. The bromoethyl aglycon was transformed into the methoxycarbonylethylthioethyl spacer, which allowed coupling of the sugars to proteins (BSA and KLH).     

Comparisons of warfarin metabolism by liver microsomes of rats treated with a series of polybrominated biphenyl congeners and by the component-purified cytochrome P-450 isozymes

R- and S-warfarin metabolite profiles (regio- and stereoselectivity) have been determined with hepatic microsomes from untreated rats and rats treated with nine individual polybrominated biphenyl (PBB) congeners, a commercial mixture of PBBs, and, for comparison with phenobarbital and 3-methylcholanthrene. The metabolic rates have been correlated with cytochrome P-450 (P-450) isozyme concentrations in the microsomes determined by immunochemical quantitation techniques (G. A. Dannan, F. P. Guengerich, L. S. Kaminsky, and S. D. Aust, (1983) J. Biol. Chem., 258, 1282–1288). The warfarin hydroxylase activities of the P-450 isozyme components of the various microsomal preparations (F. P. Guengerich, G. A. Dannan, S. T. Wright, M. V. Martin, and L. S. Kaminsky (1982) Biochemistry, 21, 6019–6030) were multiplied by the corresponding isozyme concentrations to obtain an assessment of the potential warfarin hydroxylase capacity of the microsomes, and the results were compared with actual activities. The results of these studies and comparisons indicate that substrate regio- and stereoselectivities of microsomal-bound P-450s are essentially retained on purification of the isozymes to homogeneity and reconstitution, that warfarin metabolism by microsomal preparations can be used to predict microsomal P-450 isozyme compositions, and that microsomal warfarin hydroxylase activity is greater than would be predicted based on the approx 20:1 ratio of P-450 to NADPH-P-450 reductase in the microsomes and on the known activities of constituent isozymes. Two P-450 isozymes which are induced by treatment of rats with phenobarbital appear to be more tightly linked to NADPH-P-450 reductase than does an isozyme induced by β-naphthoflavone.     

Cross-Reactions of Human Lupus Autoantibodies with 8-Methoxypsoralen Photomodified DNA Fragments

DNA fragments of around 200 base pair (average size) have been covalently crosslinked with 8-methoxypsoralen under 365 nm UV light. The photoadduct, induced antibodies in rabbits with a titer of > 1:12,800 by direct bindng ELISA. Binding data showed that the induced antibodies are conformation-specific recognizing restricted conformational change at site of crosslinking. Human autoantibodies against DNA, bound not only to native DNA but to the photomodified DNA fragment as well. In addition, binding patterns of SLE sera obtained from different patients were remarkably similar, indicating the recognition of altered conformation of the modified polymer by naturally occurring SLE anti-DNA autoantibodies.     

N NMR studies of the binding of CN with gold(I) drugs

¹⁵N NMR studies of the interaction of ¹⁵N cyanide ion with gold(I)-thiomalate (Autm) and gold(I)-thioglucose (Autg) have been carried out at pH* 7.40. The chemical shifts of the two ¹⁵N ions containing species Au(C¹⁵N)₂⁻ and RS-Au-C¹⁵N⁻ (where RS⁻ = tm⁻ or tg⁻) were identified at 265.94 and 260.30 ppm, respectively. From the broadened ¹⁵N NMR signals, approximate life times of the RS-Au-CN⁻ species were calculated.     

Does Gγ/Aγ ratio and Hb F level influence the severity of sickle cell anaemia

Sickle cell anaemia (SCA) exhibits significant variations in clinical presentation in different populations for which several genetic factors including SCA-associated -and -thalassaemias, G-6-PD deficiency and elevated Hb F level have been implicated as possible ameliorating factors. Saudi Arabia is unique in that mild and severe forms of the disease occur at a high frequency. We investigated the G/A ratio and Hb F level and correlated these values with the severity of SCA. The results showed that Hb F level varies significantly in both groups of patients with no evident correlation with the mild clinical manifestations. However, G/A ratio correlated significantly with the disease severity where a high ratio was observed in patients with the mild and a low ratio in patients with the severe disease. The results are evaluated and discussed in the light of correlation studies and regression analysis.