The renal lysosomes in acute experimental pancreatitis in dogs treated with prostacyclin (PGI2).

The inflammatory process in pancreas affects the function and structure of kidneys both by enzymatic toxemia and impairment of the renal circulation. In this study the stability of renal lysosomes in AEP in dogs treated with cytoprotective agent PGI2 was investigated. AEP was induced by injection of the bile and trypsin into the pancreatic duct; experiments were terminated after 12 hours. In lysosomal enriched subfraction of the kidney cortex (sedimenting in 15 000 x g) in untreated group (N = 5) relative free activity (r.f.a.) of cathepsins (Cs), acid phosphatase (APh) and beta-glucuronidase (BG) increased to 51,67 and 62% respectively, whereas in healthy dogs (N = 6) these activities were 20,38 and 25%. In dogs (N = 6) treated with PGI2 at the dose of 20 ng/kg/min. during 12 hrs, the r.f.a. of Cs, APh and BG was 18,40 and 49%, whereas in dogs (N = 5) additionally pretreated during 1 hr before induction of AEP with the same dose of PGI2, its values achieved 19,40 and 47% respectively. Our results suggest the stabilizing effect of PGI2 on kidney lysosomes damaged in acute experimental pancreatitis in dog. As possible mechanisms of prostacyclin action are discussed: limitation of necrotic process in the pancreas; improvement of renal haemodynamics; direct cytoprotective effect on the kidney.

Enhancements to the JET poloidally scanning vacuum ultraviolet∕visible spectrometers.

Enhancements to the JET poloidally scanning spectrometers are presented, which will aid the exploitation of the recently installed ITER-like wall in JET. They include the installation of visible filter∕photomultiplier tube assemblies and spectrometers and the replacement of large rotating mirrors in the JET vacuum with small oscillating mirrors outside. The upgrade has resulted in a more robust and reliable diagnostic than before, which is described. Drifts in the mirror angle reconstructed from quadrature encoder signals are found, a reference signal being required. The use of the small scanning mirrors necessitated the inclusion of focusing mirrors to maintain throughput into the vacuum ultraviolet spectrometers. The mirror design has taken account of the extreme sensitivity of the focusing to the grazing angle of incidence, an aspect of importance in the design of grazing incidence focusing components on future machines, such as ITER. The visible system has been absolutely calibrated using an in-vessel light source.

Pancreatic lysosomal hydrolases in acute experimental pancreatitis in dogs.

Majority of literature data support the significance of proteases activation in pathogenesis of acute pancreatitis. The ability of cathepsins to the activation of trypsinogen was shown and the labilization of lysosomes of pancreas in different models of acute experimental pancreatitis (AEP) was reported. In present work the dynamic of lysosomal changes during the course of AEP in dogs is evaluated. AEP was induced in 17 mongrel dogs by Elliot's method. Six healthy dogs served as a control group (I). Pancreatitic dogs were killed after 6 hr (G. II, n = 5), after 12 hrs (G. III, n = 5), and after 24 hrs (G. IV, n = 6 survivors). The pancreata were removed and divided into segments A (less advanced changes, [B] most advanced changes) and C (intermediate changes). The lysosomal enriched subfraction was isolated from the C segments at 15 000 X g for 20 min. The total (T) and free (F) activity of beta-glucuronidase (beta-G), acid phosphatase (AP), acid cathepsins (Cs) was estimated and the value F/T (relative free activity-r.f.a.) was calculated as an index of lysosomal stability. The progressive increase of r.f.a. of hydrolases in whole homogenate and in lysosomal enriched subfraction depending on time of AEP was observed suggesting labilization of pancreatic lysosomes. This labilization was more expressed in corresponding parts of organ with more advanced pathological changes. The differences between part A and B were most evident after 6 hrs of AEP. The labilization of lysosomes is more pronounced after 12 and 24 hrs than after 6 hrs in analogical parts of organ. These results indicate that labilization of lysosomes in pancreas correspond to the degree of pathological changes of pancreatic tissue.

Lysosomal hydrolases of dog kidney in superior mesenteric artery occlusion (SMAO) shock.

In 6 dogs with superior mesenteric artery occlusion (SMAO) shock and in 6 healthy animals the total and free activity of lysosomal hydrolases (acid phosphatase, betaglucuronidase and cathepsins) in the whole homogenate, the lysosomal enriched subfraction and the supernatant of kidneys were estimated. Statistically significant differences between the two groups were not observed. These results indicate that in SMAO shock, the stability of kidney lysosomes is well preserved during observed period.

The role of lysosomal alterations in the damage to the pancreas and liver in acute experimental pancreatitis in dogs.

The role of lysosomal hydrolases in the pathogenesis of acute pancreatitis and secondary liver injury, as an important aspect of multisystem organ failure, remains unclear. The purpose of this study was to assess the lysosomal fragility in both organs in acute experimental pancreatitis (AEP) of graded severity in dogs. In 7 dogs, the moderate (M) and in 13 dogs severe (S) variant of bile--trypsin AEP--was induced; 6 dogs were in control group (C). The 24 h survival time was 6/7 and 6/13, respectively. After that time, the dogs were sacrificed and the lysosomal enriched subfraction (L) from both organs was isolated by ultracentrifugation. The total (T) and free (F) activities of beta-glucuronidase (beta G), cathepsins (Cs) and acid phosphatase (AcP) according to Gianetto and de Duve were assayed. The fractional free activity (% F/T) was adapted as and index of lysosomal stability. The %F/T of BG in the homogenate of the pancreas in AEP(S) was higher than that in AEP(M) (92% vs. 71%, p < 0.05, and vs. 37% in C, p < 0.005). The %F/T of Cs and AcP showed a similar pattern. The %F/T of beta G in L of the liver in AEP(S) was 38% vs. 29% in AEP(M), (p < 0.05), and vs. 20% in C (p < 0.05). In AEP in dogs the %F/T activities of lysosomal hydrolases in the pancreas and liver were increased, suggesting the labilization of lysosomal membranes in severe form of this disease. Our results support the pathogenic role of lysosomal hydrolases in the damage to the pancreas and liver in acute pancreatitis.

Prostacyclin (PGI2) stabilises hepatic lysosomes during acute experimental pancreatitis in dogs.

In 15 mongrel dogs acute experimental pancreatitis (AEP) was induced by injection of bile and trypsin into the pancreatic duct. After 12 hrs in lysosomal enriched subfraction of the liver in untreated group (N = 5) relative free activity of cathepsins (Cs), acid phosphatase (AP) and beta-glucuronidase (beta G) increased to 50,62, and 53% respectively in comparison to the healthy dogs (N = 6) : 19,43 and 20%. In dogs with AEP treated with prostacyclin (PGI2) in the dose of 20 ng/kg X min for 12 hrs these activities of Cs, AP and beta G were lowered to 30,55 and 41% in comparison with the untreated group. In dogs with AEP (N = 5) additionally pretreated during 1 hr before the induction of AEP with the same rate of PGI2 i.v. infusion, the relative free activity of enzymes was similar to the treated group. After two hrs incubation of lysosomal enriched subfraction in acidic medium (pH = 5,0), the highest values of relative free activity were observed in untreated group, the difference being more pronounced in comparison with control group than before incubation. In those animals treated and pretreated with PGI2, postincubation activities were much lower than in untreated dogs. These results suggest the stabilising effect of PGI2 on hepatic lysosomes, damaged during the course of AEP in dogs.

Heparin effect on the activity of certain lysosomal hydrolases in dog pancreas (in vivo investigations).

The effect of heparin doses of 1.5 and 6.0 mg/kg of body weight on pancreatic lysosomes was investigated in vivo in dogs. Latent activity of beta-glucuronidase, acid phosphatase and cathepsins in whole pancreatic homogenate, in the subfraction sedimenting at 15 000 x g, and in the supernatant was determined as an index of lysosomal stability. In the whole homogenate a rise in the total activity of beta-glucuronidase was observed, proportional to heparin dose while there was no effect of heparin on the latent activity of beta-glucuronidase and acid phosphatase. On the other hand, the proportion of the latent activity of cathepsins in their total activity increased in heparin-treated dogs, which points to a direct stabilizing effect of the drug on pancreatic lysosomes in the dog. Investigations of subfractions gave, in part only, results approaching those obtained in the whole homogenate.

Plasma rotation induced by directed waves in the ion-cyclotron range of frequencies.

Changes of the toroidal plasma rotation induced by directed waves in the ion-cyclotron range of frequencies (ICRF) have been identified experimentally for the first time on the JET tokamak. The momentum carried by the waves is initially absorbed by fast resonating ions, which subsequently transfer it to the bulk plasma. Thus, the results provide evidence for the influence of ICRF heated fast ions on plasma rotation.