Native and oxidized low density lipoproteins modulate mesangial cell apoptosis

Hyperlipidemia has been demonstrated to contribute to hypercellularity of the mesangium in experimental animal models of glomerulosclerosis. We studied whether it also has the potential to convert a hypercellular mesangium into a hypocellular one by inducing mesangial cell (MC) apoptosis. Low density lipoprotein (LDL) enhanced (P < 0.001) mouse mesangial cell (MMC) proliferation at lower concentrations (control, 10.3 +/- 0.3 vs. LDL 100 micrograms/ml, 24.2 +/- 0.3 x 10(4) cells/ml) but augmented (P < 0.001) apoptosis at higher concentrations (control, 5.6 +/- 0.5% vs. LDL, 500 micrograms/ml 26.2 +/- 3.4% apoptotic cells/field). Oxidized (OX) LDL enhanced MMC apoptosis in concentrations of 50 to 200 micrograms/dl. There was a direct relationship between MMC apoptosis and oxidation of LDL as judged by measuring thiobarbituric acid reactive species (TBARS). Since superoxide dismutase (SOD) attenuated (P < 0.001) LDL-induced MMC apoptosis, it seems to be mediated through the generation of free radicals by mesangial cells (control, 4.3 +/- 1.5%; LDL, 200 micrograms/ml, 19.4 +/- 0.5%; LDL + SOD, 8.1 +/- 1.3% apoptotic cells/field). LDL also induced a similar effect on human mesangial cells. These studies were further confirmed by DNA fragment assays and ELISA for programmed cell death. LDL treated cells also showed enhanced mRNA expression for RSG-2, a marker for active cell death. These in vitro results provide a basis for the speculation that LDL has the potential to cause an initial hypercellular and subsequent hypocellular mesangium in the course of the development of glomerulosclerosis.     

Evaluation of anti-nociceptive effects of neuronal nicotinic acetylcholine receptor (NAChR) ligands in the rat tail-flick assay

In the present investigation, anti-nociceptive effects of neuronal nicotinic acetylcholine receptor (NAChR) ligands, (+)- and (-)-nicotine, cytisine, methylcarbamylcholine (MCC), dimethylphenylpiperazinium iodide (DMPP), and (+/-)-epibatidine were evaluated in the rat tail-flick assay both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) administration. The pharmacology of the tail-flick response to NAChR ligands after s.c. and i.c.v. routes was similar. Epibatidine was the most potent ligand examined with a longer duration of action than any other agonist. (-)-Nicotine was more active than (+)-nicotine indicating stereospecificity. ICV administration studies indicated an apparent partial agonist activity for (+)-nicotine in the tail-flick response. Tail-flick responses to NAChR agonists are independent of opioid and muscarinic pathways and appear to be mediated both by central and peripheral NAChR recognition sites. Central administration of MCC activates both NAChR and muscarinic anti-nociceptive mechanisms. Studies employing the alpha-adrenergic receptor alkylating agent, phenoxybenzamine or the noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), suggested that the NAChR-noradrenergic and NAChR-serotoninergic interactions play an important role in the tail-flick response. Studies employing a selective alpha-bungarotoxin-sensitive NAChR receptor antagonist, methyllycaconitine (MLA), suggested a minimal role for these receptors in the tail-flick response. The biochemical studies also indicated that a sub-population of NAChR receptors are located pre-synaptically on noradrenergic and/or serotoninergic pathways in the hippocampus.     

Protein accumulation in cerebrospinal fluid during -90 degrees head-down tilt in rabbit

Plasma proteins are only somewhat larger than the intercellular spaces of the cerebral microvessels that constitute the blood-brain barrier or of the choroid plexus villi that elaborate cerebrospinal fluid (CSF). We hypothesized that the integrity of these barriers in anesthetized rabbits might be compromised during head-down tilt (HDT). Plasma protein and osmolality, hematocrit, and CSF protein concentration were compared in rabbits exposed to 1 h of HDT (n = 20) and prone rabbits (n = 10). In addition, the concentration of trypan blue dye, injected intravenously at the end of HDT or the prone position, was measured in brain homogenate. Finally, arterial blood pressure was measured via a catheterized carotid artery. HDT disrupted the barrier between blood and CSF, as indicated by a significantly (P < 0.01) greater brain trypan blue concentration in the HDT rabbits [172.2 +/- 14.4 (SD) micrograms/g dry wt] than in the prone rabbits (29.8 +/- 4.4 micrograms/g dry wt). Moreover CSF protein 5 min after HDT onset was significantly increased compared with control in HDT rabbits (54.6 +/- 1.9 vs. 81.4 +/- 5.2 mg/dl; n = 8) but not in prone rabbits (55.6 +/- 2.7 vs. 57.2 +/- 5.0 mg/dl; n = 6). Changes in the plasma protein-to-hematocrit ratio in the HDT animals, but not in the prone animals, were also compatible with a loss of fluid from the vascular compartment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Presence of genomes of phage PBV-1 in the mycelia of the fungus Penicillium brevi-compactum

Progressive systemic sclerosis may be associated with focal myocardial fibrosis. Electrocardiographic abnormalities including conduction block are common in progressive systemic sclerosis but whether they are due to direct destruction of the specialized conduction tissue of the heart is uncertain. The conduction systems of 35 patients with progressive systemic sclerosis were studied. Of these 35 patients, 17 (50 per cent) had myocardial fibrosis of the type seen in progressive systemic sclerosis. In 10 of the 17, it was severe. Sinus node fibrosis was present in 13 patients and was nearly as frequent in those with as in those without the progressive systemic sclerosis myocardial lesion. Overlying pericarditis may have contributed to the fibrotic changes within the sinoatrial nodes in seven of the 13 patients. The atrioventricular node and main His bundles were normal. However, fibrotic changes were found in the proximal bundle systems in six patients. In three of the six, severe myocardial progressive systemic sclerosis was present, two had focal fibrous atrophy of the left bundle, and one had complete interruption of the right bundle. In only the latter patient was this reflected in the electrocardiogram which showed a right bundle branch block. Three patients without progressive systemic sclerosis myocardial lesions also had fibrous atrophy of a portion of the proximal left bundle branch, and in one the electrocardiogram showed an isolated left anterior hemiblock. Thus, morphologic abnormalities within the conduction system in our patients are difficult to attribute to progressive systemic sclerosis per se. Furthermore, although conduction abnormalities were more frequent in patients with myocardial disease, specific conduction system disease was not the cause in most patients. As has been noted in ischemic heart disease, the conduction system appears to be relatively spared from the myocardial changes of progressive systemic sclerosis, and the high incidence of conduction disturbances in this condition may be a consequence, rather, of damage to working myocardium.     

Topical corticosteroid therapy complicating congenital glaucoma

A 4-month-old infant with congenital glaucoma had been treated with a topical antibiotic-corticosteroid for three months. This fact complicated initial management, delaying definitive diagnosis and therapy. Topical steroid therapy in infants can produce a condition simulating congenital glaucoma. Since there is little rationale for using topical steroids to treat most infantile external disease processes, they are best avoided. When steroids are used for a prolonged period, some strategy for detecting glaucoma should be adopted.     

Flux-Based Estimation of Field Capacity

Field capacity has been defined as the water content at which the drainage flux from a soil ceases, or becomes negligible. Field capacity is most commonly estimated as the water content at a pressure head of 1∕3 bar, which ignores its flux-based nature. A number of authors have proposed estimating field capacity as the water content at a given (negligible) flux, assuming unit gradient conditions. This flux-based method of estimating field capacity is discussed and the differences between this method and the more common pressure-based method are illustrated. The drainage flux considered to be negligible will depend on the particular application; values between 10?6 and 10?8 cm∕s were considered here. The observed differences in field capacity resulting from the negligible flux range considered produce significant differences in the available water capacity. These differences directly impact the calculated drainage. The effect of available water capacity on the water budget for waste disposal facility covers at an arid and humid site was illustrated using the HELP code. At the arid site, drainage decreased by a factor of 4 (from 25 to 6 mm∕year) as the available water capacity increased from 0.101 to 0.199. At the humid site, drainage decreased from 190 to 173 mm∕year over the same range of available water capacity. Finally, a simple procedure for the determination of an appropriate value for the negligible flux is discussed. Analysis of data from a lysimeter at Coshocton, Ohio, indicated that field capacity for the lysimeter soils was associated with a negligible drainage flux of about 3 × 10?7 cm∕s.     

A numerical prediction of carter coefficient in a curved air gap

Abstract

The effect of air gap curvature on the Carter coefficient and magnetic field is studied in this article. In the analysis, a finite‐difference successive relaxation technique is employed to solve a dimensionless Maxwell equation. Constant fluxes are applied on a simplified model and the calculated Carter coefficients in the curved air gap are compared with the data in the existing literature. Flux plots, dimensionless radial flux densities in the air gap, and the Carter coefficient with normalized air gap G=0.1 and 0.2, slot numbers N=18, 24 and 36, rotor curvature K=0.24, 0.17 and 0.1, slot depths D=0.4 and 2.0, and half slot width W=0.2 to 0.8 are presented.     

Oxidation sizing of iron and iron-neodymium-boron powders

A powder sizing test developed for use on WC powders has been extended for use on iron and iron-neodymium-boron powders. In this test the particle size is derived from the rate of oxidation, because finer powders oxidize quicker. The rate of oxidation is monitored in a thermogravimetric analyser, where the powders are subjected to a controlled heating rate from room temperature to 1100 °C. If the constants from the Arrhenius law are known the powder size can be determined by comparing experimental oxidation plots with theoretical curves. For the sizing of a commercial spherical iron powder, the oxidation technique compared favourably with direct sizing using scanning electron microscopy and image analysis. The values for the activation energy of 125 kJ mol^–1 determined in this study agree with previous studies. Validation of the sizing technique on a hydrogen-decrepitated stoichiometric Nd₂Fe₁₄B powder proved difficult because it was not possible to determine a definitive size distribution independently. Metallography of partially oxidized samples showed that the process is two-stage, at low temperatures the neodymium oxidizes, and above 400 °C the powder behaves as pure iron. Theoretical curves based on one oxidation process with an activation energy of 100 kJ mol^–1 gave the best fit to the experimental curves.