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Biomedical subjects

A Shostak

Publications and source records attributed to A Shostak.

At least 37 records · Page 2Linked to original sources

Cultured rat mesothelial cells generate hydrogen peroxide: a new player in peritoneal defense?

This study was designed to examine whether rat peritoneal mesothelial cells in culture could generate hydrogen peroxide in different experimental conditions. Mesothelial cells, incubated in M-199, spontaneously released hydrogen peroxide. This process was significantly increased by addition of phorbol myristate acetate, as well as of superoxide dismutase to the medium, whereas it was substantially inhibited by catalase. Exposure of mesothelial cells to modified M-199 medium with 1.5% glucose concentration-lactated peritoneal dialysis solution did not seem to interfere either with the spontaneous release of hydrogen peroxide, or with that induced by phorbol myristate acetate. Furthermore, exposure of mesothelial cells to the glucose (4.25%) peritoneal dialysis solution in Medium M-199, was coincident with increased hydrogen peroxide generation, which was significantly higher than the spontaneous release, and not far from that observed with phorbol myristate acetate and superoxide dismutase. So far, it can be inferred from this evidence that peritoneal mesothelial cells in culture are not only endowed with the capability of producing hydrogen peroxide, but they can also be activated to do so in a way comparable to that observed in neutrophils and macrophages. This attribute is one more indication that mesothelial cells play a relevant role in the peritoneal mechanism of defense against infection. On the other hand, continuous exposure of mesothelial cells to glucose-enriched fluids, as occurs in clinical continuous ambulatory peritoneal dialysis, may well also be at the origin of a process of continuous injury, resulting from an increased hydrogen peroxide generation.

Animals↗

Treatment of surgical and non-surgical septic multiorgan failure with bicarbonate hemodialysis and sequential hemofiltration.

OBJECTIVE: Hospital mortality of patients with septic multiorgan failure (MOF) is still around 95%. The present study investigates whether this high mortality could be significantly reduced by the addition of sequential hemofiltration (SH) with bicarbonate hemodialysis (HD) to the currently used life supportive measures. DESIGN: 35 (18 surgical and 17 nonsurgical) patients, with 3 or more organ failures, had daily sessions of zero balance SH, for periods ranging from 2-22 days. MEASUREMENTS AND RESULTS: SH induced significant improvement of PaO2/100 FIO2, Apache II score, MAP, as well as blood chemistry in survivors. Dying patients had less marked improvement of blood oxygenation, non-significant changes in other variables, in addition to low MAP before and after SH, as well as marked hemodynamic unstability during the procedure. The observed hospital mortality was 38% for the surgical group, and 35.3% for the medical patients (n.s.). CONCLUSIONS: Mortality observed in this retrospective, uncontrolled study was significantly lower than that currently observed with conventional supportive therapy, with or without the addition of other forms of blood purification, e.g. CAVH and CAVHD. This improvement in results appears to be related to the property of SH to completely clear 90% of the blood from mediators of inflammation in only one passage through the hemofilter, and to better tolerance of HD done using bicarbonate buffer. A definite evaluation of this technique will be eventually reached by a programmed, appropriate sample size study, which is out of reach for one individual ICU.

Adult↗

Endocytosis and transcytosis of albumin gold through mice peritoneal mesothelium.

The present transmission electron microscopy (TEM) study was designed to investigate whether mesothelial cells of mice diaphragmatic, parietal and mesenteric peritoneum are actively coupled to the mechanisms involved in the transerosal absorption of albumin gold complexes (Alb-Au). Five albino mice were injected intraperitoneally with 0.5 ml of a suspension of Alb-Au. In three animals, in vivo fixation was done 10 minutes after injection of Alb-Au, whereas in the remaining two, fixation was performed 45 minutes after injection of the tracer. At both time intervals, a substantial part of Alb-Au complexes was observed within plasmalemmal and coated vesicles, mainly attached to the luminal aspect of the internal luminal membranes. The amount of Alb-Au contained in plasmalemmal vesicles was significantly higher than that detected in intermesothelial junctions. Plasmalemmal vesicles were observed discharging Alb-Au complexes in the submesothelial interstitium, showing a significantly higher proportion of the tracer associated with non-junctional areas. Evidence presented in this study supports the idea of local degradation of Alb-Au in mesothelial cells after endocytosis, and that of a continuously transcytotic mechanism transporting polymerized albumin across the mesothelial layer. In this sense, transcytotic vesicles could represent the large pore equivalent.

Animals↗

The cytochemical profile of visceral mesothelium under the influence of lactated-hyperosmolar peritoneal dialysis solutions.

Male albino mice had one daily intraperitoneal injection of 4.25 g/100 ml glucose concentration fluid for peritoneal dialysis at pH 5.0-5.2, for a period of 30 days. At the end of the experimental periods, mesothelial cell imprints were taken from the peritoneal layer of the anterior liver surface. Histochemical staining of imprints obtained from mice exposed to the peritoneal dialysis fluid showed a consistently increased activity of: (a) enzymes associated with the cell membrane: Na-K-ATP-ase, alkaline phosphatase and 5-nucleotidase; (b) cytoplasmic enzymes: acid phosphatase and cytochrome oxidase, and (c) a modestly increased activity of glucose-6-phosphatase. These changes, which are not far from those observed in activated mesothelial cells, suggest that exposure of mesothelial cells to high glucose concentrations of PD fluid is associated with increased production and disposal of energy to be used for maintaining the constancy of the cellular environment and, probably, for fuelling the transcellular transport of solutes of large molecular size.

5'-Nucleotidase↗

Acute and long-term changes observed in imprints of mouse mesothelium exposed to glucose-enriched, lactated, buffered dialysis solutions.

Solutions for peritoneal dialysis (PD), the hyperosmolarity of which is obtained with glucose, have been shown to initiate and maintain a situation of continuous mesothelial cell injury associated with a process of regeneration which also takes place continuously. The present study was done using the in vivo and almost in situ technique of mesothelial cell imprints. Acute exposure to 4.25% glucose solution at pH 5.2 and 7.0 induced higher mitotic activity, defective cytokinesis, and reduced cell viability. Long-term exposure (15 and 30 days) to both 4.25% glucose solutions was associated with a reduced population density, increased surface area, and lower mesothelial cell viability, regardless of the pH. The use of 1.5% glucose fluid showed that this effect was dose related. After 30 days of recovery, mesothelial cells exposed to the high-glucose solution at both pH 5.2 and 7.0 appeared repopulated by small cells and showed evidence of defective cytokinesis. So far, it appears that the alterations observed after long-term exposure of the mesothelium to PD fluid are mainly caused by the high concentration of glucose per se. The additional effects of hyperosmolarity are still unclear, whereas the eventual role of low pH, at least in the experimental model used here, can be defined as less than marginal.

Analysis of Variance↗

Loss of microvascular negative charges accompanied by interstitial edema in septic rats' heart.

We studied the effect of Gram-negative sepsis on negative charges of heart capillaries and myocardial cells. We used a rat model of multiorgan failure, with ruthenium red (RR) and polyethyleneimine (PEI) as cationic binding tracers. Twenty-four hours after induction of sepsis, negative charges had decreased in glycocalyx and basement membrane of myocardial capillary endothelial cells. There were substantial amounts of interstitial edema. Density of anionic charges in the sarcolemmal glycocalyx complex of cardiac cells was markedly reduced. Myocardial cells' mitochondria consistently showed morphologic changes, whose severity ranged between stages II and IV C of Trump. Thirteen days after induction of sepsis, capillary endothelial and myocardial cells had recovered almost completely and showed no intracellular edema. Gram-negative sepsis caused a significant reduction in negative charges normally present in the microvascular wall as well as on myocardial cells. Consequently, several membranes limiting the various compartments of heart tissue lost their structural integrity. This morphometric data could explain the development of protein-rich interstitial edema and defective cell volume regulation observed in cardiac muscle of endotoxin-shocked animals. This myocardial edema may be at the origin of the cardiac dysfunction observed in both experimental and human septic shock.

Animals↗

The Ural train-gas pipeline catastrophe: the report of the IDF medical corps assistance.

Following the destruction of two trains in the Urals 2000 km east of Moscow, as a consequence of the conflagration caused by an explosion from a leaking natural gas pipeline, 3000 people were injured;* most of them (2200) died* immediately and the others (about 800) were badly burned. At the request of the Soviet Union Government a medical military delegation was sent to give assistance to the injured people. This report describes the treatment given by the delegation to 40 patients with burns of between 40 and 90 per cent TBSA during a period of 10 days. An insight into a Soviet Union Trauma Center is given and the good treatment given by the Soviet colleagues is emphasized.

Blast Injuries↗

Protamine sulfate induces enhanced peritoneal permeability to proteins.

We present a direct link between the neutralization of anionic sites by intraperitoneal protamine and a rise in protein passage to the peritoneal cavity during isosmotic peritoneal dialysis in rabbits. Each experiment included two 1-hour exchanges. No drugs were added in the first exchange. In group A (control) there were no drugs in the second hour either. In group B, protamine (50 micrograms/ml) was added to the second exchange volume. In group C, protamine and heparin (50 U/ml) were added. In groups A and C, appearance curves of metabolites during the first (baseline) and the second (experimental) hours were not statistically different. In group B, differences for urea, glucose and uric acid were not significant, but they were highly so for protein (increase of 100%, p less than 0.01). Transperitoneal passage of albumin is substantially enhanced by protamine. Neutralization of protamine with heparin prevents this, showing that availability of anionic sites is the crucial limiting factor. Protamine did not significantly affect the transfer of small neutral molecules.

Animals↗

Anionic fixed charges in the fenestrated capillaries of the mouse mesentery.

Previous studies showed the existence of submesothelial fenestrated capillaries in the human parietal and rabbit diaphragmatic peritoneum, as well as in the mouse mesentery. The present study demonstrates the presence of electronegative fixed charges at the luminal aspect of endothelial cells, as well as long the subendothelial basement membrane of the fenestrated capillaries of the mouse mesentery. This situation will eventually preclude the transfenestral passage of anionic plasma proteins. On the other hand, fenestrated capillaries are much more permeable to water and small-molecular-size solutes than those of the continuous type. Therefore, the high hydraulic conductivity of fenestrae may well imply that a substantial part of water and small solutes leave the blood compartment through the fenestral channels.

Animals↗

Prolonged intraperitoneal dwell decreases ultrafiltration coefficient in rabbits.

In rabbits undergoing peritoneal dialysis, hypertonic (6% dextrose) dialysis solution increased the net ultrafiltration rate (UF) from 233 to 462 microL/kg/min, which was not proportional to the increment in the osmotic gradient, so the ultrafiltration coefficient decreased. As intraperitoneal dwell of hypertonic dialysate was prolonged, the gross and net UFs and ultrafiltration coefficients decreased, and the UF per dextrose absorption declined. The decrement in UF was multifactorial, including a component of fluid and solute stagnation, increasing the distance over which osmotic forces must exert their effects. Excessively hypertonic dialysis fluid should be used only briefly to achieve ultrafiltration efficiently and to avoid the high dextrose loading.

Absorption↗

Effects of histamine and its receptor antagonists on peritoneal permeability.

Peritoneal fluid and mass transfer rates were studied in rabbits undergoing control dialyses and dialyses with intraperitoneal histamine, or its receptor antagonists alone or in combination. These drugs had negligible effects on peritoneal ultrafiltration and small solute clearances. Histamine raised protein exudation from 1.6 to 2.9 mg/kg/min, an effect blocked by its antagonists which given alone did not lower protein loss. These data demonstrate the existence of histamine receptors in the peritoneal diffusion barrier and show that they do not control transport under baseline conditions, but can be blocked should abnormal histamine release occur. Increased peritoneal permeability with sterile peritonitis was unaffected by ranitidine, suggesting alternative mediators.

Animals↗