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Biomedical subjects

A Jung

Publications and source records attributed to A Jung.

At least 127 records · Page 7Linked to original sources
PubMed1988

Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate.

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Resorption↗
PubMed1987

Glutathione and peroxide metabolism in malaria-parasitized erythrocytes.

The glutathione metabolism of Plasmodium falciparum, P. vinckei and P. berghei has been investigated. Human erythrocytes with low glutathione reductase and synthetase activity are still capable of harbouring P. falciparum. Both enzymes have been demonstrated in Plasmodium spp. Moreover, evidence is given for a selenium-independent glutathione peroxidase in malaria parasites.

Animals↗
PubMed1987

Plasmodium falciparum: inhibition in vitro with lactoferrin, desferriferrithiocin, and desferricrocin.

The microbial iron chelators desferriferrithiocin and desferricrocin as well as human lactoferrin were tested in vitro against Plasmodium falciparum. The microbial chelators inhibit the growth of P. falciparum in a dose dependent way. Parasite multiplication is stopped at 25-30 microM desferriferrithiocin, whereas 60-90 microM desferricrocin are needed to exhibit the same effect. After iron saturation, the microbial chelators are ineffective. Human lactoferrin (30 microM), both iron free and iron saturated, inhibits P. falciparum. A 3-day preincubation of host erythrocytes with iron free and iron saturated lactoferrin prior to infection enhances this effect, which is therefore attributed to lactoferrin bound iron. It has been suggested that the lactoferrin/iron complex generates oxygen free radicals, which may cause membrane damage of both erythrocyte and parasite. This process can be considered to lead to growth inhibition of the parasite.

Animals↗
PubMed1986

14C-desferrioxamine B: uptake into erythrocytes infected with Plasmodium falciparum.

Plasmodium falciparum-infected human erythrocytes (early trophozoite stages) and non-infected erythrocytes were incubated in 1.7 mM 14C-desferrioxamine B (specific activity 1 microCi/2.6 mg desferrioxamine B). After 270 min the cells were washed and the radioactivity was measured in the cell pellet and, after lysis, in cytoplasm and membranes. The results indicate that Desferrioxamine B can the red blood cell and pass through the parasite membrane and that the parasites are killed by the intracellular action of the chelator.

Animals↗
PubMed1986

Stage-specific sensitivity of Plasmodium falciparum to antifolates.

Highly synchronous cultures of Plasmodium falciparum were exposed to therapeutic concentrations of sulfadoxine or pyrimethamine at different developmental stages to investigate the effect on subsequent growth. Morphological observations showed that schizont formation from uninuclear trophozoites was the only process inhibited by the drugs. Segmentation of mature schizonts, merozoite invasion and development of the ring stage remained unaffected. These results support earlier reports suggesting that DNA synthesis is most pronounced in 32-42 h old trophozoites. The possible relevance of our results to the metabolism of P. falciparum is discussed.

Animals↗
PubMed1986

Mechanisms of sulfadoxine resistance in Plasmodium falciparum.

Three possible mechanisms of resistance to sulfadoxine were investigated in resistant Plasmodium falciparum: drug uptake, metabolism and alternate pathways. Uptake of [35S] sulfadoxine was markedly reduced in resistant plasmodia. By Thin Layer Radiochromatography it could be demonstrated that plasmodia do not metabolize sulfadoxine to pharmacologically inactive forms. Metabolism of sulfadoxine to the toxic analog of dihydropteroate is reduced in resistant plasmodia. Para-aminobenzoic acid (pABA) is not an essential nutrient for sulfonamide-resistant plasmodia. Instead, they seem to be able to synthesize pABA de novo. Four enzymes of the respective biosynthetic chain were demonstrated in isolated plasmodia: 3-deoxy-D-arabino-heptulosonate-7-phosphate synthetase (EC 4.2.1.15), shikimate dehydrogenase (EC 1.1.1.25), shikimate kinase (EC 2.7.1.71) and pABA synthetase. We conclude that these three effects account for the reduced sulfonamide stress observed in the resistant parasite.

3-Deoxy-7-Phosphoheptulonate Synthase↗
PubMed1986

The mechanism of pyrimethamine resistance in Plasmodium falciparum.

The uptake of radioactive pyrimethamine by a sensitive and a resistant strain of Plasmodium falciparum, the metabolic fate of pyrimethamine inside these parasites and the kinetic properties of dihydrofolate reductase (DHFR) from both strains have been studied. Uptake of the drug was identical in both strains and no metabolite of pyrimethamine was found in either strain. DHFR from the resistant strain was 300 times less sensitive to inhibition by pyrimethamine than the enzyme from the sensitive strain, while the Michaelis constant for dihydrofolate remained unchanged and inhibition was competitive in both cases. Altered properties of plasmodial DHFR are apparently the only mechanism responsible for pyrimethamine resistance in the strain of Plasmodium falciparum studied.

Animals↗
PubMed1986

Stage-dependent inhibition of chloroquine on Plasmodium falciparum in vitro.

Morphological observation of the life cycle of the malaria parasite, Plasmodium falciparum, in highly synchronous cultures after an exposure to therapeutic concentrations of chloroquine in ring, trophozoite and schizont stages, respectively, were carried out in order to determine the influence of chloroquine on the growth of the different stages of the malarial parasites. It was found that chloroquine could not affect merozoite invasion of the erythrocytes; the ring stage was more sensitive to chloroquine than the trophozoite and schizont stages; and chloroquine in therapeutic concentrations prevented only the transformation of rings to trophozoites and could not affect the transformations of trophozoites to schizonts and schizonts to new rings. The determination of the IC50 of chloroquine showed that the IC50 of trophozoites was about 6 times as high as that of rings.

Animals↗
PubMed1985

[Tumoral hypercalcemia: physiopathology and treatment].

The regulation of plasma calcium involves many factors acting at the gut, bone and kidney levels. The mechanism leading to hypercalcemia in malignant neoplasm may well differ according to the type of tumor, the presence or otherwise of bone metastasis, the stage of the disease as well as additional factors such as the state of hydration. Increased bone resorption would certainly play an important role. However, increased tubular reabsorption of calcium could be the main hypercalcemic mechanism in some types of malignant tumor. Therapeutically, the approach has so far been to reduce the input of calcium from gut and bone and/or improve its renal clearance. Until now, the most efficient action appears to be the blockage of bone resorption. Among several bone resorption inhibitors, the diphosphonate compounds have been shown in several reports to be quite efficient in normalising calcemia.

Bone Neoplasms↗