The effects of ionizing irradiation on production of thromboxane and prostacyclin by the isolated perfused rat kidney

Exposure to whole body radiation is associated with prompt changes in urinary excretion of prostaglandins. We investigated the separate effects of radiation on rat kidney capillary and tubular system prostaglandin synthesis. Animals were irradiated to the left kidney area with a single dose of 15 Gy. One week later the rats were anesthesized, the renal artery, vein and ureter of the left kidney cannulated, and the kidney removed and perfused with Krebs-Henseleit physiological buffer at a rate of 10-12 ml/min. Effluent fluids were collected separately from the renal vein and from the ureter of irradiated and control (operated sham-irradiated animals) and were assayed by radioimmunoassays for thromboxane A2 (TXB2) and prostacyclin (6 keto PGF1 alpha). Histological examination of the irradiated kidneys showed no significant changes, and electron microscopy revealed minimal interstitial edema. In contrast to these minimal changes, TXB2 assays showed a significant increase both in the venous and ureter effluents. Following stimulation with angiotensin II in the perfusate, a further significant increase in TXB2 production was observed both by the capillary and the tubular systems. With 6 Keto PGF1 a slightly different response was seen. The basal production was increased only in the ureter effluent of the irradiated animals, while there were no changes in the release in the venous effluents. In parallel, radiation significantly increased the angiotensin II stimulated production capacity of prostacyclin by the tubular system. The response of the capillary system following irradiation may create imbalance between these two important substances and lead to the radiation effects in the renal tissue.     

Extent of Resection in Temporal Lobectomy for Epilepsy. I. Interobserver Analysis and Correlation with Seizure Outcome

The extent of resection was assessed in 45 temporal lobectomies for medically intractable epilepsy with mapped temporal lobe foci. Postoperative magnetic resonance imaging (MRI) in the coronal plane was used to quantify the extent of resection of superior lateral, inferior lateral, basal, and medial structures, including the amygdalohippocampal complex. A new 20-compartment model of the temporal lobe was used for this assessment. Blinded interobserver variability was minimal. Intraoperative measurements and maps routinely overestimated the actual extent of resection, especially of medial structures. One year after surgery, 70% of patients remained seizure-free (except for auras). Seizure-free outcome was accomplished despite varying degrees of resection, but was more likely achieved with more extensive resections in all compartments. Among patients with mesiobasal foci, seizure-free outcome correlated significantly with extent of resection of amygdalohippocampal complex. We conclude that assessment of extent of resection by postoperative MRI provides an objective basis of evaluating outcome after temporal lobectomy. It allows a rational approach to understanding of operative failures and is potentially useful in comparing efficacy of various surgical approaches.     

Some Effects of Electrical Fields on Red Blood Cells with Remarks on Electronic Red Cell Sizing

Sizing normal RBC by an electronic method showed that with certain aperture currents a skewed bimodal size-distribution curve is obtainable. In these studies some possible causes for such distributions were investigated. The experiments show that an electrical field can cause change in shape, size, and staining properties of RBC as well as lysis. Extrapolation of the results of these experiments to the conditions of the RBC sizing method indicate that these changes are not responsible for the skewed bimodal distribution. We believe, therefore, that normal RBC vary among themselves in some structural or physiologic way, not necessarily size, that was measured by this system.
The use of aperture currents within the range that displays the bimodal distribution is helpful in diagnostic practice, because the bimodal size distribution enhances the discrimination of the system for detection of simultaneously existing different red cell populations.     

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Prostacyclin (PGI2) synthetic capacity was assayed at the surface of aortas at various intervals after removal of endothelium with a balloon catheter. Results were correlated with morphologic changes in the vessel wall seen by light microscopy, scanning and transmission electron microscopy. To assay PGI2 synthetic capacity, we applied an incubation chamber to the luminal surface of the aortas; after arachidonic acid stimulation we assayed the PGI2 synthesized with a bioassay and radioimmunoassay. PGI2 synthesis in de-endothelialized aortas was determined immediately after balloon-catheter injury and at intervals of 1 h and 2, 4, 15, 35, and 70 d. PGI2 synthesis was low at 1 h and increased over time with levels at 35 and 70 d reaching that of normal artery. Scanning and transmission electron microscopy of de-endothelialized areas showed persistent absence of endothelium with formation of a neointima composed of smooth muscle cells. De-endothelialized aorta was covered with adherent platelets shortly after injury, however several days later only a few platelets adhered to the denuded surface. Results indicated that (a) endothelium is responsible for nearly all PGI2 production at the luminal surface of the normal aorta, (b) de-endothelialized muscular neointima synthesized increasing quantities of PGI2 with time after injury, and (c) increase of PGI2 production at the luminal surface of de-endothelialized aorta correlates with formation of a neointima and with the acquired thromboresistance of the aorta.     

The heart of children with steroid-resistant nephrotic syndrome: is it all podocin?

Mutations in the gene NPHS2 encoding podocin are responsible for a recessive form of steroid-resistant nephrotic syndrome (SRNS). The common phenotype is of massive proteinuria in early childhood that tends to progress to end-stage renal failure. Extrarenal manifestations have not been described. Twenty-two children with SRNS from six unrelated Arab families were found to be homozygous for the R138X mutation in NPHS2. Eighteen patients underwent cardiac evaluation at diagnosis of SRNS while they had normal BP and preserved renal function. Cardiac anomalies were detected in 16 (89%) children: Left ventricular hypertrophy in eight, pulmonary stenosis in six, discrete subaortic stenosis in two, and Ebstein anomaly and ventricular septal defect in one each. The remaining four affected individuals were assessed only once they had end-stage renal failure. They had severe left ventricular hypertrophy and experienced repeated episodes of heart failure. Two control groups were equally evaluated. The first consisted of 37 siblings without nephrotic syndrome, of whom only one carrier had a cardiac defect (P < 0.001). None of the second group, which included 22 children with persistent nephrotic syndrome as a result of other causes, had a cardiac anomaly (P < 0.001). Cardiac disorders in homozygotes for mutations in NPHS2 cannot be attributed to an association by chance or to a state of persistent nephrotic syndrome. Because human podocin mRNA is expressed in fetal heart, it is speculated that it may have a role in normal cardiac development. Cardiac evaluation is recommended at the time of diagnosis of SRNS due to mutations in podocin.     

Distribution of myosin, actin and actin-binding protein in thrombasthenic platelets

The quantity of myosin, actin, and actin-binding protein (ABP) in platelets and platelet fractions of 5 patients with Glanzmann's thrombasthenia were compared to those of normal individuals. No significant differences were observed between the average amounts of these contractile proteins in unfractionated platelets or platelet membrane obtained after osmotic shock. However, the amount of myosin was significantly decreased in the KCl extract of thrombasthenic platelets ruptured by freezing and thawing,while its specific ATPase activity was increased.     

Effect of ticlopidine on neutrophil chemotaxis in rats

The ex vivo effect of oral administration of ticlopidine on rat neutrophil chemotaxis was evaluated. Rats received either 3 oral doses (100 mg/kg body weight) of the drug, within a period of 48 h, via a gastric tube, or the drug was administered in drinking water for 14 days at a dosage of 75 mg/kg/day. Absorption of the drug was manifested by significant inhibition of adenosine diphosphate-(ADP-)induced platelet aggregation. No impairment of neutrophil chemotaxis toward zymosan-activated serum was observed in the ticlopidine-treated animals. These results indicate that concentrations of ticlopidine that significantly inhibit platelet function in rats are without effect on neutrophil chemotaxis toward zymosan-activated serum.     

The effect of long-term colchicine therapy in patients with recurrent polyserositis on the capacity of blood platelets to synthesize thromboxane A2

Thromboxane B2 (TXB) production during platelet activation was measured in 13 patients with recurrent polyserositis on long-term colchicine therapy and 10 healthy controls. Plasma colchicine concentration in patients ranged between 0.8-7.8 ng/ml (2.0-19.5 X 10(-9) M). Thromboxane production induced during aggregation by arachidonic acid or collagen and serum TXB2 levels (clotted blood, 37 degrees C, 1 h) did not differ among patients and controls. Previous studies reporting platelet function defects including anomalous TXB2 production, were performed in vitro using colchicine concentrations markedly exceeding the therapeutic range.