Influence of dietary carbohydrate on zinc-deficiency-induced changes in oxidative defense mechanisms and tissue oxidative damage in rats

The aim of this study was to determine the effect of dietary carbohydrate type on the expression of zinc (Zn) deficiency in rats with respect to tissue oxidative damage and defense mechanisms. Rats were fed diets containing adequate (+Zn) or low concentrations (-Zn) of Zn. Both fructose- and glucose-based diets were tested. Pair-fed controls were also studied to evaluate changes in the oxidative defense system which are secondary to Zn-deficiency-induced anorexia. Plasma and liver Zn concentrations and CuZn superoxide dismutase activities were lower in the -Zn rats than in the +Zn rats. Liver glutathione (GSH) and disulfide glutathione concentrations were higher in the -Zn rats than in the +Zn rats; this difference was most pronounced in the fructose groups. Liver and heart selenium glutathione peroxidase (Se-GSH-Px) activities were lower in the -Zn-fructose group than in the +Zn-fructose group. Liver Se-GSH-Px activity was higher in the fructose groups than in the glucose groups. Liver GSH reductase (GSH-Red) activity was lower in the -Zn-fructose group than in its control group. Liver glutamine synthetase activity was lower in the -Zn-glucose group and in the fructose groups than in the glucose control group. Liver thiobarbituric acid reactive substance (TBARS) production was similar among the groups. Collectively, these results support the concept that Zn deficiency can result in an impaired oxidant defense system. Based on the observation that pair-fed control animals also showed evidence of oxidative damage, we suggest that one factor that contributes to the effect of Zn deficiency is the reduction in caloric intake that occurs in these animals. Fructose feeding resulted in increased activities of several of the oxidant defense enzymes. Protein oxidative damage assessed by glutamine synthetase activity was increased by both Zn deficiency and fructose feeding.     

Electrophysiology of the marine diatom Coscinodiscus wailesii IV: types of non-linear current-voltage-time relationships recorded with single saw-tooth voltage-clamp experiments

Electrophysiological states of the marine diatom Coscinodiscus wailesii are known to change spontaneously in the temporal range of seconds. In order to assess the genuine current-voltage-time relationships of individual states in less than a second, voltage-clamp experiments have been carried out using single sweeps of saw-tooth shaped command voltages. This method is introduced with model calculations. Plotting the results in current-voltage coordinates provides convenient access to several electrophysiological entities, such as absence of drift (smoothly closed IV loops), membrane capacitance (by I jump at sign reversal of dV/dt), and ohmic conductances (in linear regions of the current-voltage relationship), as well as equilibrium voltage (internal intersection of capacitance-corrected, 8-shaped tracings) and coarse gating kinetics (rise or fall of capacitance-corrected I at sign reversal of dV/dt) of a voltage-sensitive ion conductance. From electrophysiological measurements with double-barreled glass-microelectrodes on C. wailesii, several distinct types of current-voltage loops are presented. Most of the data, including recordings from electrical excitation, can be interpreted as temporal relaxations of voltage-sensitive conductances for K⁺ and Cl⁻. A more detailed analysis of the effect of tetraethylammonium (TEA⁺) shows that 10 and 20 mM TEA⁺ inhibit the K⁺ conductance in C. wailesii only by up to about 20% but predominantly via a K⁺ outward rectifier. Received: 23 December 1998 / Revised version: 1 June 1999 / Accepted: 1 June 1999     

Two blood pressure/cardiac mass quantitative trait loci on Chromosome 3 in Dahl rats

Interval mapping was used to identify putative quantitative trait loci (QTL) for blood pressure and cardiac mass on Chromosome (Chr) 3 in F₁(S × R) × S population of 150 rats raised on an 8% NaCl diet. Two genetic markers 95.7 cM apart, D3Wox3 and D3Mco5 (tightly linked to Edn3), showed ``suggestive' linkage to blood pressure (LOD = 2.0 and 1.8 respectively). In addition, D3Wox3 showed ``suggestive' linkage to heart weight (LOD = 2.5), and D3Mco5 showed ``suggestive' linkage to body weight–adjusted heart weight (LOD = 2.1). Congenic rats (designated S.R-Edn3) were constructed by introgressing the R-rat Edn3 allele (and flanking loci) into the S strain. On a 2% NaCl diet, S.R-Edn3 rats had lower blood pressure (21.4 mm Hg, P= 0.0005) and heart weight (59 mg, P= 0.0038) compared with S rats, confirming the existence of a blood pressure QTL on Chr 3 near Edn3 even though QTL linkage analysis of blood pressure did not achieve stringent statistical criteria for significance. The results of the congenic experiment and the large distance between the two putative QTL suggest the presence of at least two independent blood pressure/cardiac mass QTL detectable on Chr 3 in the Dahl rat model of genetic hypertension. Received: 24 April 1998 / Accepted: 29 September 1998     

Human apolipoprotein E N-terminal domain displacement of apolipophorin III from insect low density lipophorin creates a receptor-competent hybrid lipoprotein

The surface of Manduca sexta low density lipophorin (LDLp) particles was employed as a template to examine the relative lipid binding affinity of the 22 kDa receptor binding domain (residues 1–183) of human apolipoprotein E3 (apo E3). Isolated LDLp was incubated with exogenous apolipoprotein and, following re-isolation by density gradient ultracentrifugation, particle apolipoprotein content was determined. Incubation of recombinant human apo E3(1–183) with LDLp resulted in a saturable displacement of apolipophorin III (apo Lp-III) from the particle surface, creating a hybrid apo E3(1–183)-LDLp. Although subsequent incubation with excess exogenous apo Lp-III failed to reverse the process, human apolipoprotein A-I (apo A-I) effectively displaced apo E3(1–183) from the particle surface. We conclude that human apo E N-terminal domain possesses a higher intrinsic lipid binding affinity than apo Lp-III but has a lower affinity than human apo A-I. The apo E3(1–183)-LDLp hybrid was competent to bind to the low density lipoprotein receptor on cultured fibroblasts. The system described is useful for characterizing the relative lipid binding affinities of wild type and mutant exchangeable apolipoproteins and evaluation of their biological properties when associated with the surface of a spherical lipoprotein.     

Biologic Response to Peripheral and Central Administration of Recombinant Human Leptin in Dogs

LEBEL, CARL, AMY BOURDEAU, DAVID LAU, AND PAMELA HUNT. Biologic response to peripheral and central administration of recombinant human leptin in dogs. Obes Res. Objective: Because leptin is believed to act within the central nervous system, the objective of this study was to test that presumption by comparing the biologic responses to recombinant human leptin (rHuLeptin) when delivered either subcutaneously or intrathecally in a large animal species, the beagle dog. Methods and Procedures: Adult beagle dogs were used for all studies (n = 3 to 14). Treatment with rHuLeptin was either as daily subcutaneous or intermittent intrathecal injections. Results: Subcutaneously administered rHuLeptin was absorbed with peak concentrations appearing at 2 to 4 hours. After intrathecal administration, cerebral spinal fluid concentrations declined in a bi-phasic manner with a terminal half-life of ?6 to 8 hours. When lean beagles were given leptin subcutaneously, at 0. 05 to 5 gkglday for up to 6 months, reductions in body weight (up to 30%) and food intake (up to 75%) were observed. Body fat loss was observed in both lean and obese dogs, and confirmed by dual energy X-ray absorptiometry and histology of adipose tissue. When rHuleptin was delivered intrathecally at 4 to 1000 μg/dose for up to 3 months, the primary effects observed were reductions in body weight and food intake. In general all findings reported in the intrathecal studies were consistent with those noted in the subcutaneous studies; however, the required intrathecal dose was substantially lower than that for subcutaneous delivery. Discussion: These studies demonstrate that both subcutaneous and intrathecal treatment of rHuLeptin was associated with effects on body weight, food intake, and body fat in dogs. These results support the concept that the central nervous system is the probable primary site of action for leptin and suggest that rHuLeptin has similar physiologic activities that influence body weight, body fat, and metabolism in large animals to those reported previously in rodents.     

Narrow hybrid zone between two subspecies of big sagebrush (ARTEMISIA TRIDENTATA: Asteraceae). IX. Elemental uptake and niche separation

The concentrations of selected elements and their biological absorption coefficients were determined for leaves from plants in native stands and reciprocal transplant gardens to determine whether niche differentiation occurs among the parental taxa and their hybrids in the big sagebrush hybrid zone in Utah. The bounded hybrid superiority model predicts such niche differentiation, while the ecologically neutral dynamic equilibrium model predicts complete niche overlap, at least in the vicinity of the hybrid zone. The concentrations of elements in the leaves of site-indigenous sagebrush and the biological absorption coefficients differed significantly between the subspecies and between either parental taxon and hybrids. Within reciprocal transplant gardens, both the elemental concentrations and the biological absorption coefficients differed among the gardens and taxa. Significant genotype-by-environment interactions were observed for several essential elements. Niche differentiation was evident as correspondence analyses ordinated the parental taxa and hybrids into separate groups even when raised in the same garden. These findings support the ecologically based bounded hybrid superiority model and suggest that the big sagebrush parental taxa and their hybrids have adapted to their respective unique habitats.