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Biomedical subjects

A Jung

Publications and source records attributed to A Jung.

At least 145 records · Page 8Linked to original sources

Plasmodium vinckei: suppression of mouse infections with desferrioxamine B.

Plasmodium vinckei kills NMRI mice within 6 days after infection. Treatment of infected animals with desferrioxamine B for 5 days was found to suppress the parasitemia in a dose-dependent manner. The desferrioxamine B-iron complex (DFO/Fe3+) was ineffective, which suggests that the iron-chelating capacity of free desferrioxamine B is the antimalarial principle. All mice survived when they were given 0.3 mg desferrioxamine B/g every 12 hr for 14 days after infection. In addition, they were resistant to reinfection for at least 8 weeks. Eight months after desferrioxamine B treatment, all mice had lost their induced immunity and were as susceptible to malaria as controls. These results illustrate the dependence of the malarial parasite on ionic iron and suggests new methods for the therapy of parasitic diseases.

Animals↗

Suppression of parathyroid secretion after administration of WR-2721 in a patient with parathyroid carcinoma.

WR-2721 is an organic thiophosphate, known as a radioprotective agent, which also inhibits parathyroid hormone (PTH) secretion and reduces the plasma calcium level in euparathyroid animals and human subjects. In this study we present evidence that WR-2721 is also able to reduce an abnormal PTH secretion in a case of parathyroid carcinoma. The intravenous infusion of a single dose (750 mg/m2) of WR-2721 was followed within 3 h by a reduction in the plasma concentration of PTH by 60%, and of Ca by about 0.45 mmol/l. These changes were associated with a diminution in urinary cAMP excretion. Based on this observation it appears that WR-2721 merits further investigation as a possible agent for the medical treatment of hyperparathyroidism.

Amifostine↗

Diurnal variation of several blood parameters in the owl monkey, Aotus trivirgatus griseimembra.

Diurnal variations in normal hemogram, total serum protein and serum iron are documented in 6 adult owl monkeys, Aotus trivirgatus griseimembra, maintained in an artificial LD 12:12 (35:0.08 lx) with light phase from 03.00 to 15.00 h Central European time. Statistically significant high amplitude rhythms occurred in total leukocyte and in eosinophil numbers with acrophases at 06.35 and 09.53 h, respectively. Erythrocyte numbers and hemoglobin concentration showed statistically significant low amplitude rhythms with almost identical acrophases. Total serum protein exhibited a 10% daily fluctuation. Serum iron concentration showed high amplitude daily variations with a 60% mean range of oscillation.

Animals↗

A simple method for measurement of intestinal calcium absorption in humans by double-isotope technique.

We describe a method for the fast calculation of total fractional calcium absorption (TFCaA) by the double-isotope technique (45Ca orally and 47Ca intravenously). The gamma- and beta-activities of plasma or urine samples were measured simultaneously. 47Ca activity was obtained by a gamma-ray spectrometer after exclusion of scandium 47. The 45Ca activity was measured directly by subtracting the 47Ca plus 47Sc component from the total beta-activity. In addition, 45Ca activity was determined after 8 weeks, to allow for 47Ca and 47Sc decay. There was good correlation between these two methods of measuring 45Ca activity. TFCaA was calculated both by deconvolution taken as a reference method and from the equilibrium quotient 45Ca/47Ca observed in several blood or urine samples collected at different times. The most convenient sampling time for calculation of this ratio was reappraised, taking into account the type of solution ingested orally (water or milk). The results indicate that simultaneous counting of gamma- and beta-activities of an appropriate plasma or urine sample provides a good and rapid measure of the calcium absorption. This method is considered to be useful as a clinical tool.

Adult↗

[Dichloromethylene diphosphonate in the treatment of lytic bone metastases].

Dichloromethylene diphosphonate (Clodronate) has powerful activity against osteoclasts. We studied its effects on calcium balance in patients with malignant osteolytic lesions. Ten normocalcemic patients with advanced metastatic bone disease or myeloma were evaluated in a baseline 20-day calcium balance and kinetic study. They were then randomized to a clodronate or placebo regimen, treated intravenously for two weeks and orally for a month, and finally re-evaluated in another 20-day balance and kinetic study, conducted while they were still receiving treatment. The results show that both calcium balance and calcium absorption increased from base line in the clodronate group and that these changes were significantly different from those in the placebo group. There was a marginal decrease in bone resorption in the clodronate group and no change in bone accretion. Our results suggest that clodronate may be a useful adjuvant in managing metastatic bone disease.

Adult↗

Inhibition by diphosphonates of bone resorption induced by the Walker tumor of the rat.

An animal model is described to test the effect of diphosphonates, which are powerful antiosteolytic agents, against bone tumors. This model consists of injecting Walker tumor cells into one iliac artery of a series of rats while the contralateral artery is clamped during the injection, and waiting 7 days to obtain a significant destruction of the femur and tibia of the rats. In most of the animals, after this delay, extensive lesions are observed macroscopically by X-ray and histologically. The parenteral administration of three diphosphonates, dichloromethylene diphosphonate, ethanehydroxydiphosphonate , and aminopropanediphosphonate , at 16 and 160 mumol/kg/day, protects the bones by decreasing the extent of osteolysis. This protective effect is seen both in the tumor-injected leg and in the contralateral leg and is significant when compared to nontreated animals. The most active of the drugs was dichloromethylene-diphosphonate; ethanehydroxydiphosphonate and aminopropanediphosphonate were less active, especially when given at the higher dosage. All diphosphonates produce a marked decrease of the number of osteoclasts; ethanehydroxydiphosphonate at the higher dosage, induced a large increase of nonmineralized bone. These results are discussed in light of recent clinical work, showing that this animal model is a useful tool to test the effect of new drugs against osteolysis of cancer.

Animals↗

Use of dichloromethylene diphosphonate in metastatic bone disease.

Dichloromethylene diphosphonate (clodronate), a new compound, has powerful activity against osteoclasts and has been used successfully to treat hypercalcemia associated with cancer. We studied its effects on calcium balance in patients with malignant osteolytic lesions. Ten normocalcemic patients with advanced metastatic bone disease or myeloma were evaluated in a baseline 20-day balance and calcium kinetic study. They were then randomized to a clodronate or placebo regimen, treated intravenously for two weeks and orally for a month, and finally reevaluated in another 20-day balance and kinetic study, conducted while they were still receiving treatment. The results show that both calcium balance and calcium absorption increased from base line in the clodronate group and that these changes were significantly different from those in the placebo group (mean change [+/- S.D.] in calcium balance [clodronate vs. placebo], 203.8 +/- 140.1 vs. -65.2 +/- 98.8 mg [5.1 +/- 3.5 vs. -1.6 +/- 2.5 mmol] of calcium per day, P less than 0.01; change in calcium absorption, 158.8 +/- 158 vs. -38.2 +/- 96.0 mg [4.0 +/- 4.0 vs. -1.0 +/- 2.4 mmol] per day, P less than 0.05). There was a marginal decrease in bone resorption in the clodronate group and no change in bone accretion. Our results suggest that clodronate may be a useful adjuvant in managing metastatic bone disease.

Bone Neoplasms↗

Unilateral nephrectomy and 1,25-dihydroxyvitamin D3.

Several renal functions respond to nephron loss by a compensatory adaptation. Whether the production of 1,25(OH)2D3 also adapts to a renal mass reduction is still a matter of controversy. In the present study we have investigated in rats the influence of unilateral nephrectomy, in both the acute (48 hr) and chronic (2 to 6 weeks) state, on plasma 1,25(OH)2D3 level measured by competitive protein binding assay. In the acute state no difference in plasma 1,25(OH)2D3 level between sham-operated (SHAM) and unilateral-nephrectomized (UNI-NX) rats was found. The presence of the thyroparathyroid glands was not required for maintaining plasma 1,25(OH)2D3 at a normal level 48 hr after UNI-NX. In the chronic state in rats fed at 1.1% Ca diet, plasma 1,25(OH)2D3 (means +/- SEM) was 94 +/- 4 in SHAM and 98 +/- 8 pM in UNI-NX. In rats fed a 0.1% Ca diet it was 252 +/- 16 in SHAM and 239 +/- 20 pM in UNI-NX. Analysis of 3H-1,25(OH)2D3 plasma decay curve indicated that in UNI-NX under a high calcium diet the normalization of plasma 1,25(OH)2D3 appears to be entirely due to an increase in production, whereas under a low calcium diet part of it may also result from a moderate decrease in the elimination rate. In conclusion, this study indicates that unilateral nephrectomy does not affect the level of plasma 1,25(OH)2D3 even under a calcium restriction challenge. This compensatory adaptation appears to be independent of parathyroid hormone.

Animals↗

Polyamine excretion in the urine of cancer patients.

The polyamines putrescine, spermine, spermidine and cadaverine were determined in the urine of 56 cancer patients, most of whom suffered from breast or lung tumours. The excretion of spermine and putrescine was increased versus controls in a group of various cancers with metastases. The excretion of spermine, spermidine and cadaverine was increased in lung cancer without metastases. Polyamines were analysed in the urine of six women with breast cancer, before and after mastectomy. The excretion of putrescine, spermine and cadaverine was lower 6 to 9 months after the operation than before.

Adult↗

Effects of lactose on intestinal calcium absorption in normal and lactase-deficient subjects.

The effect of lactose on intestinal calcium absorption was studied in 12 normal-lactase subjects and 7 lactase-deficient subjects. Calcium absorption was compared by using the double isotope technique with or without the presence of an oral load of 50 g of lactose in each subject. The kinetic parameters were measured by the deconvolution method. In the normal lactase group, the lactose prolonged the duration of absorption at a maximum rate and therefore increased the total fractional calcium absorption from 0.224 +/- 0.039 to 0.356 +/- 0.076 (p less than 0.001). In the lactase-deficient subjects, the lactose decreased the total absorption from 0.255 +/- 0.039 to 0.209 +/- 0.032 (p less than 0.005); this effect resulted in a decrease of the maximum absorption rate. There was no significant difference between the two groups when calcium was ingested alone. These results indicate that the effect of lactose on calcium absorption is dependent on intestinal lactase activity.

Adult↗

[Activity of the glutathione redox system in human erythrocytes at various ages].

Human erythrocytes were separated into three groups according to their density and age by centrifugation in a continuous Percoll gradient. The specific activities of glucose-6-phosphate dehydrogenase, catalase, glutathione peroxidase, glutathione reductases as well as the glutathione and selenium content were highest in the youngest cell and uniformly decreased by about 20-30% in the eldest group. The age-dependence of superoxide dismutase was much more pronounced. The malondialdehyde content taken as an estimate for lipid peroxidation showed an inverse age dependence and increased by 35% in the eldest cell population. Red blood cells from 10 anemic patients exhibited less glutathione and also less malondialdehyde, while GSH-peroxidase and GSSG-reductase contents were higher. The parameters showed similar age profiles as in healthy subjects. The findings support the concept of lipid peroxidation as one of the causal events in red cell aging, but do not allow to deduce the involvement of a single enzyme related to the glutathione redox cycle in this process.

Adult↗

[[Clodronate therapy of hypercalcemia caused by hyperparathyroidism].

The diphosphonates, powerful agents which inhibit osteolysis, have been used parenterally with success to treat malignant hypercalcemia. 4 cases of anatomically confirmed primary hyperparathyroidism (age of patients 58-78 years) were admitted with a serum calcium of over 4 mmol/l in one case, over 3,5 mmol/l in a second case and over 3 mmol/l in the other two. The patients received an infusion of isotonic saline and dichloromethylene-diphosphonate (clodronate) parenterally in a dose of 500 mg a day. Serum calcium began to fall in all four patients 48 hours after the treatment was started. Intravenous clodronate therefore appears to be the treatment of choice for parathyroid crises and allows surgery of the adenomas in better metabolic conditions.

Aged↗

The use of percoll gradients, elutriator rotor elution, and mithramycin staining for the isolation and identification of intraerythrocytic stages of plasmodium berghei.

Intraerythrocytic parasites of Plasmodium vinckei and Plasmodium berghei were separated according to their developmental stages using discontinuous Percoll gradients. Contaminating nucleated blood cells such as leukocytes were removed by elutriation centrifugation. The stages were unequivocally identified in smears using a newly developed DNA-specific staining procedure with mithramycin and fluorescence microscopy. This stain can also be used to detect parasites in human blood of very low parasitemias. The combination of methods described has many possible applications in immunologic and biochemical parasite research.

Animals↗

Biochemical findings in blood of aged patients with femoral neck fractures: a contribution to the detection of occult osteomalacia.

A study was made in Geneva of 44 patients with femoral neck fractures and no risk factor of osteomalacia to determine concentrations of 25OHD3, calcium, phosphorus, alkaline phosphatase, albumin, and globulins in blood. The results were compared with those obtained for control groups of adult and aged subjects, as well as of 21 subjects operated on for hip osteoarthritis. For the detection of occult osteomalacia, femoral head bone tissue from 14 patients with fractures was examined by histomorphometric methods. In more than a third of the cases, 25OHD3 and serum albumin values were lower than those found for adult and even aged control subjects. Some slight histological signs of osteomalacia were observed in 1 patient with a femoral neck fracture, but there was no correlation between the histologic and the blood data. In practice, when dealing with aged people with no obvious risk of osteomalacia, it is important that a systematic antiosteomalacia treatment consisting of large supplements of vitamin D be avoided and that the conditions of diet and living be carefully controlled.

Adult↗

Comparison of two parenteral diphosphonates in hypercalcemia of malignancy.

The two diphosphonates, ethane-hydroxy-diphosphonate (EHDP) and dichloromethylene-diphosphonate (Cl2MDP) were injected into 30 patients with one or multiple episodes of hypercalcemia caused by osteolytic metastases. All patients responded well to the treatment after a men delay of two days. Cl2MDP was slightly more efficient than EHDP, but there was no difference in serum calcium measured after five days of therapy with Cl2MDP or after 10 days of EHDP: in both cases, the calcium level was normal. No acute or long-term side effect has been observed. Parenteral diphosphonates may well be the treatment of first choice against malignant hypercalcemia.

Adult↗