Determinants of plasma homocyst(e)ine in patients with nephrotic syndrome

Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria.     

Changes of plasma volume and plasma composition in water-deprived rats

Summary Plasma volume, hematocrit, protein and electrolyte concentrations in plasma were measured in control and water-deprived rats every three days after starting the experiment until the 15th day. Plasma volume variations, as related to body weight, suggest that water loss from plasma was proportional to total body water at three days and after 9 days of water deprivation. Greater plasma water than body water loss was found during the period between 3 and 9 days. Plasma protein and electrolyte variations suggest that during water deprivation there is a loss of protein, sodium and potassium from plasma, which is proportionally less than that of plasma water. Potassium, calcium and inorganic phosphorus were lost proportionally to plasma water. The variations in plasma volume changes were partially explained as due to variations in plasma protein and electrolyte concentrations.     

Failure of averaging in the construction of a conductance-based neuron model

Parameters for models of biological systems are often obtained by averaging over experimental results from a number of different preparations. To explore the validity of this procedure, we studied the behavior of a conductance-based model neuron with five voltage-dependent conductances. We randomly varied the maximal conductance of each of the active currents in the model and identified sets of maximal conductances that generate bursting neurons that fire a single action potential at the peak of a slow membrane potential depolarization. A model constructed using the means of the maximal conductances of this population is not itself a one-spike burster, but rather fires three action potentials per burst. Averaging fails because the maximal conductances of the population of one-spike bursters lie in a highly concave region of parameter space that does not contain its mean. This demonstrates that averages over multiple samples can fail to characterize a system whose behavior depends on interactions involving a number of highly variable components.     

The effect of amiloride on sodium and potassium fluxes in red cells

1. The effect of amiloride on the influx and efflux of (24)Na and (42)K in red cells was studied. The drug was added to the bathing Ringer or else incorporated in resealed ghosts.2. Amiloride does not inhibit the active or the passive (ouabain insensitive) extrusion of (24)Na.3. Amiloride inhibits the influx of (24)Na into red cells by 70%.4. Whether added to the inside or to the outside of the cells amiloride has no effect on the efflux of (42)K.5. Amiloride does not modify the uptake of (42)K from control Ringer. This uptake is strongly inhibited by the removal of Na. Amiloride has no effect on the extent of this inhibition.6. It is concluded that amiloride specifically inhibits the passive penetration of Na, and has no effect on the Na-K-pumping mechanism. However, at the concentration which inhibits 70% of the influx, amiloride fails to produce an observable effect on the ouabain-insensitive Na-efflux.7. On the basis that the information obtained could be extrapolated to other membranes, the effect of amiloride on epithelial membranes is discussed.     

The aniridia-Wilms tumor association: The critical role of chromosome band 11p13

The role of del (11)(p13) as a cause of aniridia, with and without Wilms tumor, is strengthened by demonstration of this chromosome aberration in 3 patients: monozygous twin girls, both of whom have aniridia and mental retardation and one of whom has a Wilms tumor; and an unrelated boy with aniridia and ambiguous genitalia. The break points defining the interstitial deletion for the twins are 11p13 and 11p15.1, while for the boy they are 11p1302 and 11p14.1. These patients and their karyotypes substantiate the critical importance of chromosome band 11p13 (or its hemizygous representation) in the development of aniridia and an associated Wilms tumor diathesis, as had been suggested previously (Riccardi VM, Sujansky E, Smith AC, Francke U, (1978): Pediatrics 61, 604-610).     

The oxidizing agent tertiary butyl hydroperoxide induces disturbances in spindle organization, c-meiosis, and aneuploidy in mouse oocytes

It has been recently proposed that a concomitant generationof oxidative stress of oocytes with increasing maternal agemay be a major factor responsible for the age-related increasein aneuploid conceptions. As a preliminary step in the testingof this hypothesis, we need to confirm that oxidative stressin itself can induce errors in chromosome segregation. In orderto achieve this goal, germinal vesicle (GV)-stage mouse oocytesfrom unstimulated ICR and (C57BLxCBA) F₁ hybrid female micewere matured in vitro for 9 h for metaphase I (MI) oocytes or16 h for metaphase II (MII) oocytes in the presence of varyingconcentrations of the oxidizing agent tertiary-butyl hydroperoxide(tBH). MII oocytes from (C57BLxCBA) F₁ hybrid mice were fixedand C-banded for karyotyping analysis. MI and MII oocytes fromICR mice were fixed and stained with the DNAfluorescent probe4',6-diamidino-2-phenylindole (DAPI) to detect abnormalitiesin chromosomal distribution. Meiosis I and meiosis II spindlesfrom ICR mice were visualized by confocal immunofluorescencemicroscopy. Data from these experiments demonstrate that in-vitroexposure of mouse oocytes to tBH during meiosis I reduces thelength (pole-to-pole distance) and width (diameter at the equatorof the spindle) of meiosis I and meiosis II spindles. This reductionis associated with an increase in the percentage of oocytesshowing chromosome scattering and clumping on the MII plate,and of aneuploidy (hyperhaploidy) in MII oocytes. However, tBHat the concentrations used in the present study has only a minimalnegative effect on the frequency of meiotic maturation. Theseresults suggest that oxidative stress during meiotic maturationin vitro may induce chromosomal errors that are undetectablein the living oocyte and whose developmental consequences maybecome manifest after fertilization. aneuploidy/meiosis/mouse oxidative stress/spindle/tertiary butyl hydroperoxide