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In mammals, the renal medulla is in a hypertonic environment related to the renal concentrating mechanism. Renal cells accumulate osmolytes such as betaine to protect cells from the perturbing effect of high concentration of electrolytes. Hypertonicity-induced cell death and the effect of betaine were investigated in Madin Darby canine kidney (MDCK) cells.

8-iso-prostaglandin F2 α(8-iso-PGF2 α), a representative isoprostane, has been reported to be a reliable marker for oxidant stress in vivo. To examine if 8-iso-PGF2αis generated in patients with acute myocardial infarction (AMI), we measured the level of immunoreactive 8-iso PGF2 αin the great cardiac vein as well as classical eicosanoids, 6-keto-prostaglandin F1α(6-keto-PGF1 α) and thromboxane B2(TXB2) in the process of urgent coronary balloon angioplasty. Fourteen patients with anterior AMI were divided into two groups: the totally occluded (n=7) and the already perfused groups (n=7). In the former, transient elevation of 8-iso-PGF2αwas observed immediately after the angioplasty, i.e. the ratio of post-angioplasty level to pre-level was approximately 2.4 for 8-iso-PGF2 α, 14 for 6-keto-PGF1 α, and 5 for TXB2. In the already perfused group, the levels of these eicosanoids were unchanged. In the totally occluded group, peak creatine phosphokinase in a peripheral vein was correlated with the level of 8-iso-PGF2α(r2=0.841, P<0.01), but not with those of the other two eicosanoids. In conclusion, transcardiac 8-iso-PGF2 αgeneration is a reliable marker for the size of myocardium exposed to oxidant stress.

Solute-free water diuretics (aquaretics) that antagonize hydrosmotic vasopressin 2 (V2) receptors may be useful in treating diseases in which water is retained. An orally active, nonpeptide, selective V2 antagonist (OPC-31260) was administered in six dose steps (3, 15, 30, 60, 100 and 200 mg) to six healthy, normally hydrated men to investigate the aquaretic effects in comparison with 12 placebo-treated control subjects (two at each dose). All subjects tolerated all six doses without serious clinical side effects. OPC-31260 increased the first 6-hr hypotonic urine volume dose-dependently. Administration at 30 mg raised the 6-hr urine volume to 2 times, 100 mg to 3 times and 200 mg to 4 times (1828.0 +/- 130.2 ml/6 hr) that of the placebo group (470.4 +/- 52.1 ml/6 hr). The drug increased urine flow maximally between 1 and 1.5 hr at all doses (e.g., 10.0 +/- 0.7-10.8 +/- 0.4 ml/min at 60-200 mg). The drug rapidly lowered urine osmolality for 4 hr, particularly between 60 and 90 min (e.g., 72.3 +/- 2.3 and 62.3 +/- 5.1 mOsm/kg at 100 and 200 mg, respectively). In marked hypotonic diuresis, mean free-water clearance of the 6-hr urine increased dose-proportionally into the positive range, reaching 2.82 +/- 0.21 ml/min at 200 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

A hepatic malignant tumour composed of both hepatocellular and cholangiocellular elements was studied histologically, immunohistochemically and electron microscopically in an 18-year-old Thoroughbred mare. Bile canaliculi and alpha-fetoprotein were useful in identifying the hepatocellular element, and mucin and keratin were good markers of biliary differentiation. The simultaneous presence of bile canaliculi and mucin-producing cells in most of the neoplastic lesions suggested that this tumour arose from a stem cell with capacity to differentiate into hepatocytes and biliary epithelium.

Locally activated renin angiotensin system plays an important role in the progression of the glomerular diseases. In order to understand the local effect of overexpressed angiotensin II in the glomerulus in situ, we introduced human genes for renin and angiotensinogen into the rat kidney by hemagglutinating virus of Japan-liposome procedure. Three days after transfection human renin was detected in the glomeruli by immunohistochemistry. Seven days after transfection, extracellular matrix was expanded in the glomeruli and α-smooth muscle actin was expressed in the mesangial cells. These results suggest that locally activated renin angiotensin system induces glomerular sclerosis and a phenotypic change in mesangial cells.

Myocardial infarction was produced in 29 anaesthetized mongrel dogs by a closed-chest coronary occlusion technique. A two-dimensional echocardiographic examination (2-D echo) was carried out just before occlusion and again 48 h after occlusion. Many cross-sectional images were recorded by a video-tape recorder. The applied site of the probe was fixed in an intercostal space and the direction of the ultrasonic beam was tilted stepwise from the basis to the apex. The animals were sacrificed at 49 hours after occlusion. The hearts were removed, quick frozen, sliced into radiating sections and stained with nitroblue tetrazolium (NBT). The outline of dyssynergy, including dyskinesis, akinesis or extreme hypokinesis, was traced with a tablet digitizer by two specialists. The three-dimensional image of dyssynergy in the left ventricular wall was reconstructed by a computer in spherical co-ordinates and assumed to be made of numerous triangular pyramids. The volume of dyssynergy was calculated quantitatively as the sum of volumes of these numerous triangular pyramids. The volume of dyssynergy seen in 2-D echo correlated well over a wide range with the volume of infarction determined by NBT staining.

Involvement of microtubules in the cellular action of vasopressin was studied by physiological and biochemical procedures. The inhibitory effect of 10(-4) M colchicine on the hydro-osmotic response of the toad bladder to 2 mM cyclic AMP was completely blocked by an increase in the concentration of calcium in the serosal bathing medium from 1 to 8 mM. Most of the colchicine-binding activity of extracts of the bladder epithelial cells was recovered by DEAE-Sephadex chromatography in a procedure similar to that used to isolate tubulin of bovine brain. Sodium dodecyl sulfate urea and urea gel electrophoresis of the DEAE-Sephadex fraction from the bladder epithelial cells yielded bands that corresponded to those of bovine brain tubulin. When 8 mM CaCl2 was present in an incubation mixture, the binding of colchicine to tubulin from the bladder epithelial cells and bovine brain was significantly inhibited. However, 1 mM CaCl2 did not affect the binding of colchicine to tubulin. Although the present study supports the concept that microtubules and calcium play an important role in the cellular action of vasopressin on the toad urinary bladder, the mechanism by which calcium blocks the inhibitory effect of colchicine on the hydro-osmotic response to cyclic AMP could not be elucidated.

Urine from 5 renal transplant recipients treated with frusemide was analyzed for unchanged frusemide (F), glucuronidated frusemide (G) and 4-chloro-5-sulfamoylanthranilic acid (CSA) by HPLC.

This paper describes a surface crack growth simulation using a new mesh generation technique. The generated mesh is constituted of all hexahedral elements. Hexahedral elements are suitable for an analysis of fracture mechanics parameters, i.e. stress intensity factor. The advantage of a hexahedral mesh is good accuracy of an analysis and less number of degrees of freedoms than a tetrahedral mesh. In this study, a plural crack growth simulation is computed using the hexahedral mesh and its distribution of stress intensity factor is investigated.