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Biomedical subjects

V Mirkovitch

Publications and source records attributed to V Mirkovitch.

At least 55 records · Page 3Linked to original sources

[Is functional demand a condition without which the pancreatic auto transplant can not survive in the dog's spleen?].

Two groups of mongrel dogs underwent intrasplenic autotransplantation of pancreatic tissues prepared from the head and tail of the organ. In the first group (12), the operation was terminated by the removal of the rest of the gland. In the second group (8), total pancreatectomy was done 6-8 months after autotransplantation. The first group of dogs became spontaneously normoglycemic after ten days of moderate hyperglycemia; their insulinemia increased significantly during a glucose loading test. The second group of dogs never became normoglycemic but remained vivacious; insulin level in their splenic vein increased moderately only after glucose injection. Microscopically, exo- and endocrine pancreatic tissues were seen in the spleens of the first group of dogs; in the spleens of the second group of dogs, only a few degenerating B cells were observed. These results suggest that the temporary hyperglycemia following autotransplantation of pancreatic tissues is a functional demand: it is necessary for ultimate survival and function of transplanted B cells.

Animals↗

[Role of the bile in lesions of the intestinal mucosa above a mechanical occlusion].

In dogs, the principal lesion in the ileal mucosa above a mechanical obstruction is the induction of a secretory state in which there is a net loss of water and electrolytes into the intestinal lumen. The role of stagnated bile as a possible agent provoking this secretion was explored by ligating the common bile duct and diverting the bile by means of an anastomosis between the gall bladder and the ileum distal to the obstruction. Seven days after creation of an obstruction with bile derivation, the functional and morphological changes in the obstructed loop were almost identical to those occurring in animals with obstructions without bile diversion. The secretory response above the obstruction continued unabated. These results suggest that the secretion in the obstructed intestine is not influeced by the presence of bile.

Animals↗

Alterations in the dog renal tubular epithelium during normothermic ischemia.

Dog kidneys were subjected to one, two, or three hours' normothermic ischemia in situ and were then excised for biochemical and histological evaluation. The uptake of para-aminohippurate (PAH) by cortical slices progressively decreased with prolongation of the ischemia, but active transport was never abolished. Glycine uptake and oxygen consumption were only reduced to a modest extent by the ischemia. The intracellular ion levels were drastically altered, with loss of potassium and gain of sodium and chloride, and considerable increases in tissue water were observed. Acid phosphatase was liberated by the whole organ into the venous blood and by the incubated slices into the incubation medium, but both biochemical and histochemical techniques showed that the total quantity of the enzyme in the cells was hardly changed. The histochemical reaction product was localized exclusively in the lysosomes. Morphological damage was slight after one or two hours' ischemia, but more pronounced after three hours, when some cells were seen to be detached from the basement membrane. These relatively minor changes seem insufficient to predict the ultimate fate of the organ after ischemia.

Acid Phosphatase↗

Formation and fate of fibrin clots in the biliary tract: a clinical and experimental study.

Fibrin clots may form in the biliary tract from hemobilia or in inflammatory disease. There is a wide variation in the clinical course of such clots which is exemplified by 9 patients. They may either dissolve through fibrinolysis, get ejected into the intestine, remain and obstruct the biliary tract, or may even transform into gallstones. In order to elucidate the mechanisms involved, the behavior of blood clots in bile was studied in vitro. A model was constructed of the biliary tract and, drained by a T-tube, where human bile circulated with a flow rate resembling that in vivo. When a small amount of human blood was injected, it flowed immiscibly to the lowest level, displaced the bile, and formed a clot of pure blood. Even a minor bleeding may thus form a coagulum. This is different from the mixed clot of blood and bile that forms in experiments simulating major hemorrhage. These findings are related to clinical experience and especially to the disappearance of "retained stones" with or without the use of dissolving agents.

Biliary Tract↗

Intrasplenic autotransplantation of canine pancreatic tissues. Maintenance of normoglycaemia after total pancreatectomy.

In mongrel dogs, the horizontal part of the pancreas was infiltrated with collagenase, cut in pieces, incubated with collagenase, rinsed twice by centrifugation or sedimentation, and implanted into the spleen of the same animal. The operations were terminated by the removal of the rest of the pancreas. Of 26 operated dogs, one died because of a duodenal perforation, five developed severe hyperglycaemia without remission, and 20 were long-term normoglycaemic survivors followed for up to 10 weeks. These 20 animals became spontaneously normoglycaemic in the course of the first 10 postoperative days. Later, during glucose loading tests, the pattern of blood sugar values was the same in the transplanted animals as in those of a group of non-operated dogs, but the insulin release, although immediate, attained half the control values. The plasma insulin in the splenic vein was more than seven times higher than in the peripheral circulation. Splenectomies performed in seven animals were followed by severe hyperglycaemia and death. Light and electron microscopy demonstrated the presence of the intact endocrine and exocrine pancreatic tissues in the spleens of all animals investigated. It is concluded that laborious separations of endocrine from exocrine tissue are not mandatory for ulterior endocrine function, and that in an animal larger than rodents it is possible to obtain a diabetes-preventing function after the transplantation of only a part of the gland.

Animals↗

Functional and structural characteristics of the jejunum and ileum in the dog and the rat.

The dog jejunum is a much denser tissue than the ileum, with a greater weight per unit length and higher proportion of mucosal tissue. Morphometric analysis reveals longer and wider villi, deeper crypts and larger enterocytes in the jejunal mucosa. Uptake of phenylalanine or beta-methyl-glucoside by tissue slices in vitro is slightly greater in jejunal than in ileal tissue. The levels of acid phosphatase and alkaline phosphatase in the individual enterocytes are significantly greater in the jejunum, according to quantitative histochemical analysis. The absorption of water, sodium, potassium, chloride and glucose in vivo is significantly smaller in the jejunal than in ileal loops, particularly when expressed in terms of unit mucosal weight. Sodium and water absorptions are stimulated by glucose at both sites, but the stimulation is significantly greater in the ileum. Opposite results have been obtained in rats where the transport of phenylalannie in vitro is greater in the ileum, but water, electrolyte and glucose absorption in vivo is greater in the jejunum.

Acid Phosphatase↗

Pancreatic transplantation. Absence of diabetes in dogs after total pancreatectomy and intrasplenic autotransplantation of pancreatic tissue.

Two simple, rapid, and reproducible techniques of pancreatic tissue preparation produced favorable results after just part of the gland was autotransplanted in totally pancreatectomized animals. It is probable that the short and less traumatic treatment in vitro was responsible for the sufficient yield of viable islets. Moreover, the results show convincingly that the complete separation of endocrine from exocrine pancreas is not mandatory to insure adequate endocrine secretion. The spleen, an organ of no vital importance having a rich blood supply and belonging to the portal circulation, was a very suitable experimental implantation site, which permitted thorough evaluation of the tissue preparation techniques. These favorable results were not conditioned by the splenic tissue itself, because similar results have been obtained in dogs when the tissues were implanted into the liver via the portal vein.

Animals↗

The roles on intraluminal oxygen and glucose in the protection of the rat intestinal mucosa from the effects of ischaemia.

Rat ileal loops were subjected to 15 minutes ischaemia by clamping both mesenteric and collateral vessels, after which the functional capacity of their mucosae was assessed according to their ability to accumulate phenylalanine "in vitro". Groups of intestines were rinsed before being subjected to ischaemia. Independent and additive protective effects were observed when the rinsing buffer was oxygenated and/or when it contained glucose. Indeed, an oxygenated, glucose-containing buffer afforded full protection to the mucosa, whereas a nitrogenated, glucose-free buffer had no action.

Animals↗

Enhanced non-electrolyte uptake in vitro by the dog jejunal mucosa in the cholera-toxin-induced secretory phase.

A characteristic secretory response in the dog jejunumis observed following three hours' perfusion with cholera toxin. When this mucosa in the secretory phase is examined in vitro, the steady-state accumulation of phenylalanine and beta-methyl-glucoside is considerably enhanced. Since the initial rates of influx of these substrates are unchanged and the tissue ion contents are the same as normal, it is concluded that the increase in steady-state uptake may be attributed to a change in the rate of efflux of the substrates across the baso-lateral membrane of the cell. This change might be related to the reported collapse of the intercellular channels when the intestine is in a secretory state.

Animals↗

The consequences of ischaemia after mechanical obstruction of the dog ileum.

A mechanical obstruction was produced in the dog ileum, and four days later, loop of intestine above and below the occlusion were subjected to one hour's ischaemia. This led to widespread morphological and functional damage of the epithelium, indistinguishable from the response of the normal intestine. The recovery of the mucosa of both loops after the ischaemia followed exactly the same pattern as when there was no occlusion superimposed: The transport capacity for phenylalanine in vitro was entirely restored, whereas that of beta-methyl-glucoside, together with oxygen consumption and lactate production, remained depressed; morphometric examination revealed that the recuperating mucosa had smaller villi, shorter crypts and smaller epithelial cells than the contiguous untouched tissue. These results suggest that the regenerative potential of the crypts could not be obliterated by one hour's ischaemia, either in the presence of a noxious obstruction fluid above the occlusion, or in the atrophic mucosa below it.

Acid Phosphatase↗

The functional response of the dog ileum to one hour's ischaemia.

1. The function and structure of dog ileal mucosa was examined immediately after arterial ischaemia for 1 h and 1, 3 or 7 days after the trauma. 2. Immediately after the ischaemia, there was a net movement of water and ions into a luminal perfusate in vivo. One day later, there was no net movement of water and electrolytes but net absorption returned on the third day. 3. Active transport of phenylalanine or beta-methylglucoside by mucosal strips in vitro was abolished immediately after the trauma but was largely restored 1 day later. There was a close correlation between glucose absorption in vivo and beta-methylglucoside uptake in vitro. 4. Morphological study revealed pronounced desquamation of enterocytes immediately after the trauma. The regenerating mucosa had shorter villi and crypts, and lower enzyme activities assessed histochemically 1 day later. Most parameters had returned to normal by the third post-operative day.

Acid Phosphatase↗

Morphology and function of the dog ileum after mechanical occlusion.

1. Complete mechanical occlusion of the ileum was produced in dogs and the loops above and below the obstruction were examined functionally and morphologically 4 or 7 days later. 2. The intraluminal pressure in the occluded loop never exceeded 8 cm water. 3. The mucosa above the obstruction secreted water and ions into the lumen in vivo, though it absorbed glucose normally. Mucosal slices also absorbed amino acids and monosaccharides normally in vitro. 4. The mucosa below the obstruction absorbed ions and glucose in vivo and non-electrolytes in vitro to a slightly smaller extent than normal intestine. 5. The morphological changes above the occlusion included shorter, plumper villi and shorter crypts, a reduction in histochemically stainable brush-border enzymes, but an increase in acid phosphatase. Below the obstruction, there was atrophy of the villi and crypts and reductions in all enzymes studied. 6. The results suggest that the mucosa above the occlusion possesses an intact and almost normal epithelial layer, but that it has been stimulated to secrete in vivo, presumably by intraluminal factors. Below the obstruction, true atrophy of the mucosa has promptly developed.

Acid Phosphatase↗

The healing of liver wounds.

Cases of traumatic hemobilia are often characterized by a protracted history with recurrent episodes of hemorrhage over many years. It seems that while the liver regenerates quickly and profusely it heals slowly and poorly. This is in contradistinction to the kidneys where lesions often heal within a short time. In order to investigate the cause of this peculiar behavior a series of experiments was performed where local lesions were produced in the musculature, in the kidneys and in the liver of dogs. The healing process was studied at different intervals. There was essentially no difference between the rate and character of healing in the three localities. As the lesions that produce hemobilia are open to the biliary tract, another series of experiments was performed where the healing took place in presence of bile. The effect of this was striking with a very diminished production of fibrinous exudate, granulating tissue and fibrous scar.

Animals↗