2,4-D-Induced Changes in the K+ Uptake of Wheat Roots at Different pH Values

The effects of an auxin herbicide, 2,4-D, at a concentration of 0.01 mM, on the K⁺ uptake and efflux of excised roots of wheat (Triticum aestivum L. cv. Rannaya) were investigated at different pH values. The K⁺ movement was monitored with a K⁺ (⁸⁶Rb) tracer. In parallel experiments the ATPase activities of microsomal fractions were determined by the inorganic phosphate liberation method. 2,4-D inhibited the K⁺ uptake especially at low pH, irrespective of whether Ca²⁺ was present or not. No marked changes were observed in the K⁺ efflux properties at pH values above 4. The inhibitory effect on K⁺ uptake exhibited a correlation with the hydrocarbon solubility of the herbicide, but not with the 2,4-D-induced decrease of the ATPase activity. It is suggested that 2,4-D exerts a non-specific effect on the lipid-protein interactions, giving rise to a generalized alteration of the transport barrier properties of the plasma membrane even at as low a concentration as 0.01 mM.     

Kininogen and Kinin in Experimental Spinal Cord Injury

Activation of the kallikrein-kinin system has been implicated in the pathogenesis of vasogenic brain edema and posttraumatic vascular injury. We determined the levels of kininogen and kinin in an experimental spinal cord injury model in the rat. Kininogen content in traumatized cord segments increased in a time-dependent manner. Western blot analysis showed that the kininogen in traumatized cord comigrates with 68K low-molecular-weight kininogen or T-kininogen. Trypsin treatment of the kininogen in traumatized cord released both bradykinin and T-kinin, which were separated by HPLC and quantified with a kinin radioimmunoassay. Endogenous kinin levels in the frozen spinal cord also increased up to 40-fold 2 h after injury as compared with controls. The results demonstrate an increased accumulation of kininogen and its conversion to vasoactive kinins in experimental spinal cord injury.     

Calorimetric and x-ray diffraction studies of rye glucocerebroside mesomorphism.

Glucocerebrosides (GlcCer) isolated from the leaves of winter rye (Secale cereale L. cv Puma) differ from the more commonly investigated natural and synthetic cerebrosides, in that greater than 95% of the fatty acids are saturated and monounsaturated hydroxy fatty acids. Isomers of the trihydroxy long chain base hydroxysphingenine (t1(8:18 cis or trans)) and isomers of sphingadienine (d18:2(4trans, 8 cis or trans)) comprise 77% and 17%, respectively, of the total long chain bases. The phase behavior of fully hydrated and dry rye leaf GlcCer was investigated using differential scanning calorimetry (DSC) and x-ray diffraction. On initial heating, aqueous dispersions of GlcCer exhibit a single endothermic transition at 56 degrees C and have an enthalpy (delta H) of 46 J/g. Cooling to 0 degrees C is accompanied by a small exothermic transition (delta H = -8 J/g) at 8 degrees C. On immediate reheating, a broad exothermic transition (delta H = -39 J/g) is observed between 10 and 20 degrees C in addition to a transition at 56 degrees C. These transitions are not reversible, and the exothermic transition rapidly diminishes when the sample is held at low temperature. Using x-ray diffraction, it was determined that the endotherm at 56 degrees C represents a transition from a highly ordered lamellar crystalline phase (Lc) with a d-spacing of 57 A and a series of wide-angle reflections in the 3-10 A range, to a lamellar liquid crystalline (L alpha) phase having a d-spacing of 55 A and a diffuse wide-angle scattering peak centered at 4.7 A. Cooling leads to the formation of a metastable gel phase (L beta) with a d-spacing of 64.0 A and a single broad reflection at 4.28 A. Subsequent warming to above 15 degrees C restores the original Lc phase. Thus, rye GlcCer in excess water exhibit a series of irreversible transitions and gel phase metastability. Dry GlcCer undergo an initial heating endothermic transition at 130 degrees C, which is ascribed to a transformation into the HII phase from a two phase state characterized by the coexistence of phases with disordered (alpha) and helical (delta) type chain conformations but of unknown lattice identity: An exotherm at 67.5 degrees C observed upon subsequent cooling is of unknown origin. Since an undercooled HII phase persists down to 19 degrees C, the exotherm may derive in part from an alpha-to-delta type chain packing conformational change especially under slow cooling conditions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of Basal Gastric Acid Secretion on the Pharmacodynamics of Ranitidine

Twelve patients with inactive ulcer disease were administered placebo and ranitidine via bolus and continuous intravenous infusions, at doses ranging from 50 every 8 h, to 12.5 mg/h for 24 h. Gastric acid was collected for 20 min each h for 24 h, and ranitidine serum concentrations were measured ± every 2 h, during each of the six study periods. Cosinor analysis of gastric acid secretion during placebo treatment revealed a significant circadian rhythm in all subjects. Mesor acid output ranged from 1.7 to 11.6 mmol/h (mean 5.6 ± 2.8 mmol/h) and the amplitude ranged from 0.7 to 6.5 mmol/h (mean 2.8 ±1.6 mmol/h). Peak acid output (acrophase) occurred at 10 p.m. ± 3 h. A pharmacodynamic model, relating ranitidine serum concentration to hourly acid secretion, was derived, which incorporated the circadian change in basal acid output. Data for this fractional response model included basal acid secretion-as determined by time of day, measured acid secretion, and associated serum ranitidine concentration. The 50% inhibitory concentration (IC₅₀) for ranitidine ranged from 10-75 ng/ml, with a mean of 44 ng/ml. The variation in IC₅₀ and in basal acid secretion combined to produce a wide variation in the pharmacodynamic response to ranitidine. The model-predicted serum concentrations, required to maintain acid secretion at 0.1 mmol/h, ranged from 250 to 1550 ng/ml, at the time of peak evening acid secretion. Despite a constant degree of acid inhibition by ranitidine during the day, higher serum concentrations are required during times of peak acid output to maintain adequate suppression of hydrogen ion secretion.     

Pulmonary and leg VO2 during submaximal exercise: implications for muscular efficiency.

Insights into muscle energetics during exercise (e.g., muscular efficiency) are often inferred from measurements of pulmonary gas exchange. This procedure presupposes that changes of pulmonary O2 (VO2) associated with increases of external work reflect accurately the increased muscle VO2. The present investigation addressed this issue directly by making simultaneous determinations of pulmonary and leg VO2 over a range of work rates calculated to elicit 20-90% of maximum VO2 on the basis of prior incremental (25 or 30 W/min) cycle ergometry. VO2 for both legs was calculated as the product of twice one-leg blood flow (constant-infusion thermodilution) and arteriovenous O2 content difference across the leg. Measurements were made 3-5 min after each work rate imposition to avoid incorporation of the VO2 slow component above the lactate threshold. For all 17 subjects, the slope of pulmonary VO2 (9.9 +/- 0.2 ml O2.W-1.min-1) was not different (P greater than 0.05) from that for leg VO2 (9.2 +/- 0.6 ml O2.W-1.min-1). Estimation of "delta" efficiency (i.e., delta work accomplished divided by delta energy expended, calculated from slope of VO2 vs. work rate and a caloric equivalent for O2 of 4.985 cal/ml) using pulmonary VO2 measurements (29.1 +/- 0.6%) was likewise not significantly different (P greater than 0.05) from that made using leg VO2 measurements (33.7 +/- 2.4%). These data suggest that the net VO2 cost of metabolic "support" processes outside the exercising legs changes little over a relatively broad range of exercise intensities. Thus, under the conditions of this investigation, changes of VO2 measured from expired gas reflected closely those occurring within the exercising legs.     

Carcinogen-induced alteration of DNA structure

We have prepared covalent complexes between defined length DNA fragments and a diol epoxide derivative of the carcinogenic polycyclic aromatic hydrocarbon, benzo(a)pyrene. We have studied the structure of these complexes, using transient electric dichroism, circular dichroism, fluorescence quenching, thermal denaturation, polyacrylamide gel electrophoresis, and nuclease digestion. Our observations suggest that th covalently bound carcinogen is intercalated within the helix, forming a wedge-shaped complex. Binding of the carcinogen distorts the structure of the DNA over a region extending beyond the immediate binding site. The most striking aspect of this distortion is that it produces a bend in the helix.