The effects of the clinically used diuretics amiloride (an inhibitor of Na+/H+ exchange) and bumetanide (an inhibitor of Na+, K+, Cl- co-transport) were tested on the cytotoxicity of estramustine and ...bleomycin in cultured fibroblasts. Both estramustine (50 micrograms/ml) and bleomycin (10 micrograms/ml) reduced the number of surviving clones. Amiloride (100 microM) but not bumetanide (100 microM) partly protected against the cytotoxic effect of both estramustine and bleomycin. The protective effect of the combination of amiloride and bumetanide was not stronger than the effect of amiloride alone. Amiloride or bumetanide alone did not affect the clonal survival. It is suggested that the protective effect of amiloride is not mediated by an effect of the molecular mechanism of cytotoxicity but may rather be due to changes in cellular metabolism and/or drug handling.
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The effect of probenecid on frusemide‐induced diuresis and hyperglycaemia was studied in mice.
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Probenecid, a known inhibitor of tubular secretion of organic anions in the kidney, strongly reduced ...the diuretic response to frusemide (25 or 200 mg kg−1 body weight). This effect of probenecid appeared to be dose‐dependent up to 240 mg kg−1 body weight, at least at the lower concentration of frusemide.
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Pretreatment with probenecid (240 mg kg−1 body weight) potentiated the hyperglycaemic effect of frusemide (25 or 200 mg kg−1 body weight).
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The results show that probenecid has opposite effects on frusemide‐induced diuresis and hyperglycaemia in mice. It is suggested that the acute hyperglycaemic effect of frusemide is not directly linked to diuresis.
The effect of furosemide on carbohydrate metabolism was studied in ob/ob mice. Intraperitoneal injection of a single dose of furosemide (200 mg/kg body weight) into fasted mice resulted in acute ...hyperglycaemia and two days after such a single dose, the mice showed fasting hyperglycaemia and glucose intolerance. Pancreatic islets from mice that had been injected with furosemide (200 mg/kg body weight) two days prior to the in vitro experiments showed increased basal (3 mmol/1 D-glucose) and decreased glucose-stimulated (20 mmol/1) insulin release. Islets from furosemide- or saline-injected animals showed no difference in islet insulin content. The results show that furosemide has both acute and long-term effects on carbohydrate metabolism in ob/ob mice. It is suggested that this, at least in part, is due to an effect on the pancreatic beta-cells.
The effects of loop diuretics on 36Cl- uptake was tested in isolated beta-cell-rich pancreatic islets. Bumetanide reduced the 36Cl- influx and the levorotatory form of ozolinone reduced both the ...influx and equilibrium content of 36Cl- in the islets, whereas the dextrorotatory form was largely inactive. The data suggest that the beta-cells are equipped with a loop diuretic-sensitive system for 36Cl- uptake and that this system is confined to a sterically well-defined structure.
A single-step assay for serum glucose measurements is described. The assay is based on the phosphorylation of D-glucose by glucokinase and the measurement of ATP consumption by firefly luciferase. ...The luminescence is recorded in an ordinary liquid scintillation spectrometer. The use of stable reagents and a stable final signal (light emission) makes it possible to analyze a large number of samples in each assay run. The assay is of particular value when repeated serum glucose determinations are performed on samples from small laboratory animals.
: We used 86Rb+ (K+ analogue) to study potassium influx during the interaction of highly specific 5‐HT3‐receptor antagonists, ondansetron and granisetron, with the effects of the anticancer drug, ...estramustine phosphate, on P31 mesothelioma cells. Estramustine phosphate (80 mg/l, 142 μmol/l) for 120 min. reduced 86Rb+ influx by 18.7%. The reduction was inhibited by ondansetron (0.1 μmol/l), but augmented by granisetron (0.1 μmol/l). Serotonin (1.0 μmol/l) antagonized ondansetron inhibition and restored granisetron‐augmented reduction of estramustine phosphate‐induced 86Rb+ influx to the level of the drug itself. Estramustine phosphate inhibited cellular Na+, K+, 2Cl− ‐cotransport activity whereas Na+, K+, ATPase activity was unaffected. Ondansetron blockade of estramustine phosphate‐induced reduction of 86Rb+ influx was due to increased Na+, K+, ATPase and Na+, K+, 2Cl−‐cotransport whereas augmentation of estramustine phosphate‐induced reduction of 86Rb+ influx by granisetron, or combination of 5‐HT3 receptor antagonists with serotonin was due mainly to inhibition of cellular Na+, K+, ATPase activity. Thus, ondansetron possesses a distinct ability to reverse K+ influx of tumour cells exposed to estramustine phosphate whereas granisetron does not, due to different effect on cellular Na+, K+, ATPase and Na+, K+, 2Cl− ‐cotransport activity. Highly 5‐HT3 receptor‐specific antiemetic agents may have different effects on ion transport of tumour cells during treatment with cytotoxic drugs.
I dag lever 80 procent av patienterna med cancer i barn- och ungdomsåren fem år efter diagnos.
Ungefär 6 000–7 000 individer i Sverige är före detta barncancerpatienter.
Sena komplikationer till ...sjukdom och behandling ses hos 60–70 procent av överlevarna.
Extra utsatta är de med hjärntumör, de som strålbehandlats och vissa grupper som stamcellstransplanterats.
Inte alla som behandlats för cancer i barn- och ungdomsåren drabbas av sena komplikationer.
En kohortstudie bestående av alla i Norden som under 20 års ålder insjuknade i cancer (n ≈55 000) åren 1943–2008 har påbörjats 2010.
Riktlinjer för uppföljning efter barncancer baserat på given behandling har tagits fram av Svenska arbetsgruppen för långtidsuppföljning efter barncancer (SALUB).
The 5-year survival for children and adolescents with cancer in developed countries is now 80 % and as a result of this, the number of adults who were treated for cancer in childhood is steadily increasing. Studies have shown that 60-70 % of survivors have at least one late complication after their disease and/or its treatment, with as yet no plateau in increased incidence. Most affected are survivors of brain tumours, those who received radiation therapy and some groups of survivors after stem cell transplantation. Problems include increased late mortality, second malignant neoplasms, endocrinological matters including infertility, cardiac and pulmonary issues and neurocognitive problems. A Nordic cohort study (Nordic Childhood Cancer Study, NCCS) is starting 2010 with the largest number of survivors yet followed. Recommendations for follow-up have been produced in North America and the United Kingdom and for Sweden by the working group for long-term follow-up after childhood cancer (SALUB).
The effects of furosemide on fasting serum glucose, glucose tolerance and pancreatic islet morphology were studied in ob/ob mice of two age groups, 3 months and 8 months. A single dose of furosemide ...(200 mg/kg body weight) induced acute hyperglycaemia in the young (3 months) as well as the old (8 months) ob/ob mice. Two days after the furosemide injection the glucose tolerance was markedly impaired in older animals, whereas it was normal in younger animals. Glucose tolerance in old mice varied markedly between individuals and showed two patterns. Thus, in one group of 8 months old mice, fasting serum glucose was elevated and glucose tolerance was very poor, whereas in the other group it was at least as good as in the saline-injected controls. Histological analysis showed normal islet morphology in furosemide-treatment young mice but an inflammatory reaction in islets from furosemide-injected old animals. A significant correlation between the degree of islet abnormality and glucose tolerance was observed. The data suggest that susceptibility to develop furosemide-induced long-term glucose intolerance is associated with the development of the obese-hyperglycaemic syndrome rather than being linked to the inheritance of the ob/ob genome as such.
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