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Biomedical subjects

I Romslo

Publications and source records attributed to I Romslo.

At least 91 records · Page 5Linked to original sources

Effects of hemorrhagic shock on gastric blood flow and acid secretion in cats.

Anesthetized cats were cannulated and successively bled to arterial pressures of 100, 75 and 50 mmHg. The pressure was maintained at each level for 20 min. One group of animals was given 16 mu . kg-1 . h-1 of pentagastrin and another group 2 mg . kg-1 . h-1 of cimetidine throughout the experiment. Blood flow was determined by means of the microsphere distribution technique using spheres 14 +/- 1 micrometer in diameter. At each pressure level 15 min sample of gastric juice were collected. Twenty ml of saline was instilled into the stomach and withdrawn together with the gastric juice. Adenosine triphosphate (ATP) content and enzymatic activity (LD, ASAT) of the gastric mucosa and blood pH, pCO2 were determined at 140 and at 50 mmHg. In both pentagastrin and cimetidine treated cats gastric mucosal blood flow decreased and the vascular resistance increased markedly when the pressure was lowered by bleeding from 140 to 100 mmHg. On further bleeding to 50 mmHg only slight additional flow reduction occurred and the vascular resistance remained constant. Under shock blood flow was higher and the resistance lower in pentagastrin than in cimetidine treated animals. In pentagastrin treated animals a parallel decrease in acid secretion and mucosal blood flow occurred under shock. Cimetidine inhibited acid secretion both at normal blood pressure and under shock. The ATP content of the mucosa did not decrease, no morphological changes of the mucosa occurred and there was no leakage of cellular enzymes during the period of hypotension.

Adenosine Triphosphate↗

Porphyrin-sensitized photodynamic damage of isolated rat liver mitochondria.

The respiration rates and the respiratory control ratios of isolated rat liver mitochondria have been measured following exposure to 0--160 kJ/m2 of near-ultraviolet radiation (blacklight) in the presence of low concentrations of porphyrins (0.1--0.2 mumol/l). Depending on the light dose, the concentration and the type of porphyrin, the following sequence of reactions occurred: uncoupling and inhibition of oxidative phosphorylation, energy dissipation, inhibition of respiration and swelling and disruption of the mitochondria. The detrimental effects could not be elicited in the absence of oxygen, neither could they be elicited by porphyrins or light alone. At equimolar concentrations, the effectiveness of the porphyrins as photosensitizers were: deuteroporphyrin greater than protoporphyrin much greater than coproporphyrin greater than uroporphyrin. The results may be of importance to explain the skin lesions seen when porphyrins of different hydrophobicity accumulate in the skin.

Animals↗

Uptake of protoporphyrin IX by isolated rat liver mitochondria.

Rat liver mitochondria accumulate protoporphyrin IX from the suspending medium into the inner membrane in parallel with the magnitude of the transmembrane K+ gradient (K+in/K+out). Only protoporphyrin IX taken up in parallel with the transmembrane K+ gradient is available for haem synthesis. Coproporphyrins (isomers I and III) are not taken up by the mitochondria. The results support the suggestion by Elder & Evans [(1978) Biochem. J. 172, 345-347] that the prophyrin to be taken up by the inner mitochondrial membrane belongs to the protoporphyrin(ogen) IX series. Protoporphyrin IX at concentrations above 15 nmol/mg of protein has detrimental effects on the structural and functional integrity of the mitochondria. The relevance of these effects to the hepatic lesion in erythropoietic protoporphyria is discussed.

Animals↗

Studies on the efflux of metalloporphyrin from rat-liver mitochondria. Effect of albumin, globin, haemin and haemoglobin.

The mechanism by which metalloporphyrins escape from mitochondria has been studied in isolated rat-liver mitochondria using Co-deuteroporphyrin as the model compound. During the first 10--15 min of incubation the efflux is about 10% of the total amount of Co-deuteroporphyrin synthesized. The efflux then increases to a second steady-state leve of 25--35% after 30--45 min of incubation. The efflux is inversely correlated to the energy state of the mitochondria. Globin at concentrations less than 0.4 mumol/l enhances the efflux of Co-deuteroporphyrin, but has no effect on the degree of energy coupling or on the rate of Co-deuteroporphyrin synthesis. The effect of globin can be competitively inhibited by adding haemin. Haemin (0.5--1.0 mumol/l) when added to the medium in the absence of globin reduces the efflux of Co-deuteroporphyrin by 20--30%, but has no effect on the metal-chelatase activity. Neither albumin nor haemoglobin increases the efflux of Co-deuteroporphyrin from intact mitochondria. The results suggest that the efflux of metalloporphyrin is regulated in part by the energy state of the mitochondria and in part by the presence of metalloporphyrin-binding ligants and unattached haemin in the incubation medium.

Animals↗

Uptake of iron from transferrin by isolated rat-liver mitochondria mediated by phosphate compounds.

1. Isolated rat-liver mitochondria accumulate iron from transferrin at neutral pH by a mechanism which is markedly stimulated by small-molecular-weight polyphosphate compounds. The efficiency of the phosphate compounds decreases in the order: pyrophosphate > ATP > GTP > 2,3-bis-(phospho)glycerate > phosphate. 2. The uptake has a very low energy dependence, and it does not depend on the hydrolysis of ATP or the saturation of transferrin, but it increases in parallel to the concentration of iron to reach a saturation level of 800-1200 pmol iron/mg protein. 3. Following a chase with unlabelled transferrin (125I)-labelled transferrin bound to the mitochondria remains constant, whereas the progressive uptake of 59Fe levels off. 4. During reincubation of iron-loaded mitochondria up to 30% of the iron is mobilized in the presence of ascorbate and ATP (or apotransferrin). 5. The results suggest that iron is mobilized from transferrin by the polyphosphate compounds outside the mitochondria in a subsequent reaction.

Adenosine Triphosphate↗

Effect of zinc on protoporphyrin induced photohaemolysis.

Zinc is readily inserted into protoporphyrin suspended either in a salt-sucrose buffered solution or endogenously present in red cell haemolysate in erythropoietic protoporphyria. Red cells from healthy persons were incubated with metal-free protoporphyrin or zinc-protoporphyrin and irradiated with light at 360-470 nm. The photohaemolysis was significantly less with zinc-protoporphyrin compared with that of the metal-free protoporphyrin. The results are discusssed in relation to the possibility of using zinc as a photoprotective and hepatoprotective agent in erythropoietic protoporphyria.

Animals↗

Studies on the mobilization of iron from ferritin by isolated rat liver mitochondria.

Rat liver mitochondria and rat liver mitoplasts mobilize iron from ferritin by a mechanism which depends on a respiratory substrate (preferentially succinate), a small molecular weight electron mediator (FMN, phenazine methosulphate or methylene blue) and (near) anaerobic conditions. The release process under optimized conditions (approx. 50 mumol/1 FMN, 1 mmol/l succinate, 0.35 mmol/1 Fe(III) (as ferritin iron), 37 degrees C and pH 7.40) amounts to 0.9--1.2 nmol iron/mg protein per min. The results suggest that ferritin might function as an intermediate in the cytosolic transport of iron to the mitochondria.

Animals↗

Stool porphyrins determined by high pressure liquid chromatography and by fractional hydrochloric acid--ether extraction.

When stool copro- and protoporphyrin were quantitated by spectrophotometry, after fractional hydrochloric acid-ether extraction, up to 30% of the protoporphyrins were recovered in the coproporphyrin extract. In disorders with elevated stool protoporphyrin excretion (e.g. erythropoietic protoporphyria), this method therefore may give falsely elevated coproporphyrin values. When the stool porphyrins were determined by high pressure liquid chromatography there was no carry-over of protoporphyrin to coproporphyrin. The recoveries were 82 and 87%, and the coefficients of variation 5.6 and 3.1% for proto- and coproporphyrin, respectively. Moreover, in specimens containing a more complex mixture of porphyrins, a complete separation of the C2-C8 porphyrins and porphyrin isomers was obtained in a single run. High pressure liquid chromatography should therefore be considered the method of choice to obtain a quantitative profile of stool porphyrins in the routine laboratory.

Chemical Fractionation↗

Serial determination of serum ferritin in children with acute lymphoblastic leukemia. Evaluation of its usefulness as a prognostic index.

Thirty children with acute lymphoblastic leukemia were monitored with serial serum ferritin determinations for up to 17 months. In children with acute lymphoblastic leukemia before initiation of therapy, or in relapse, the mean serum ferritin concentration was 636 microgram/l. In children who went into primary remission. the mean serum ferritin concentration fell from 265 microgram/l prior to start of treatment, to 161 microgram/l after 3 months of treatment. Five patients relapsed. Their serum ferritin levels prior to the relapses ranged from 7 to 135 microgram/l. At the time of relapse a further increase in serum ferritin was found in only 2 of the children. Thus, whereas high serum ferritin levels may signal disease activity in acute lymphoblastic leukemia, a normal serum ferritin level does not exlude disease activity or impending relapse.

Adolescent↗

Reduced mucosal blood flow and acid secretion related to accelerated healing of gastric ulcer in rats after omentectomy including partial gastric devascularization.

Gastric ulcers were produced in rats by local application of acetic acid to the serosal surface of the stomach. In half of the animals the greater omentum was excised just before the application of acid. Gastric mucosal blood flow was estimated by means of the (14C)-aniline clearance technique. Gastric acid secretion was determined under basal conditions and under pentagastrin stimulation. Removal of the greater omentum resulted in accelerated healing of the gastric ulcers. Maximal acid output and mucosal blood flow were found to be decreased in omentectomized animals 24 h after ulcer induction. 3 weeks later the secretion and blood flow in omentectomized animals did not differ significantly from the values of the control animals. The accelerated ulcer healing in omentectomized animals is assumed to be due to decreased acid secretion resulting from decreased mucosal blood flow following partial devascularization of the stomach.

Animals↗

Plasma estriol, progesterone, cortisol, placental lactogen and alpha-fetoprotein in a pregnancy with an anencephalic fetus followed from the seventh week till term.

Concentrations of total estriol, progesterone, cortisol, human placental lactogen and alpha-fetoprotein were measured in maternal venous plasma at regular intervals from the seventh week of pregnancy until term in a woman with an anencephalic fetus. Except for the first trimester, during which the values were in the lower normal range, the concentration of estriol was constantly subnormal. The "physiological" rise in cortisol levels was absent. Progesterone and HPL were both within the low normal range. The levels of alpha-fetoprotein were transiently raised during the 13th--25th weeks of pregnancy.

Adult↗

Studies on the uptake of porphyrin by isolated rat liver mitochondria.

1. The uptake of deuteroporphyrin by isolated rat liver mitochondria proceeds by two different mechanisms, a passive binding, and a mechanism sensitive to CCCP plus valinomycin, with different pH, temperature and time dependencies. 2. The CCCP plus valinomycin-sensitive uptake of deuteroporphyrin parallels the transmembrane potassium gradient ([K+in]/[K+out]). 3. Only that deuteroporphyrin taken up in parallel to the transmembrane potassium gradient is accessible to ferrochelatase. 4. The uptake of deuteroporphyrin at high concentrations is followed by series of damaging effects on the mitochondria: uncoupling, dissipation of the mitochondrial energy potential, increased ion permeability and leakage of endogenous potassium. 5. The detrimental effects of porphyrins at high concentrations on mitochondrial structure might explain the apparently unrelated metabolic aberrations characteristic of certain porphyric diseases.

Animals↗