摘要:

Abstract:Development of resistance against the highly toxic Cd++ion has been described earlier both in animals, cell cultures and in bacteria. In this paper we have tested if decreased intracellular concentration of Cd plays a role in resistance to Cd in three mammalian cell cultures. The cells originated from different tissue and from two different species. Cd‐resistant and corresponding “wild‐type” strains were used. The results from all three lines show essentially the same, namely that there is no significant difference in Cd content between the Cd‐resistant and the non‐resistant cells. The resistant cells from all three lines grow continuously with a cellular Cd‐content which is several times higher than that killing all cells of the non‐resist

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01592.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Cardiac toxicity of the new anthracycline antitumour antibiotics violamycin BI (V) and carminomycin (C) was studied in comparison with daunorubicin (D). Rabbits were intravenously given total doses of 0.1–1.5 mg/kg V or C, and 0.64–18 mg/kg D, respectively, twice weekly for one month. When examined two to six days, two and four weeks, respectively, after the last drug administration the gross findings consisted of hydropericard, hydrothorax and ascites in some animals. Histologically, loss of striation and focal necrosis of cardiac muscle cells and subsequently chronic inflammatory reactions and/or proliferation of mesenchyma cells were mostly found. These alterations were somewhat more pronounced in rabbits treated with V than in animals received D or C. At equitoxic doses of the antibiotics tested the ultrastructural lesions in the myocardial cells were altogether less marked after treatment with D than with C o

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01593.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Albino rats were given intraperitoneally manganese chloride (Mn2+, 4 mg/kg) daily for a period of 30 days. Manganese significantly inhibited the lipid peroxidation potential of treated rat brain without altering the contents of iron and ascorbic acid, the two prooxidant factors.In vitrolipid peroxidation studies in the fresh and heated brain homogenates showed almost a non‐enzymatic mechanism of inhibition by this metal ion. 30 μM Mn2+concentrations completely inhibited the formation of malonaldehyde (MDA) at 3 hours of incubation. Iron was found to reverse, to some extent, the effect of manganese onin vitrolipid peroxide formation in the mitochondrial fraction of brain and at concentrations of 5 μM Fe2+the amount of MDA formed is comparable to that observed with 1 μM Fe2+in the mitochondrial fraction without manganese. These observations suggest that the central nervous system toxicity of manganese may not be associated with acceleratedin vivolipid peroxidation. However, the mechanism of iron induced reversal onin vitroinhibition of lipid peroxidation by manganese is not understood, at pre

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01594.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Tracheal smooth muscle obtained from ovalbumin‐sensitized guinea pigs contracted with micromolar concentrations of tartrazine and indomethacin. The contractions were slightly reduced by clemastine, but were completely blocked by the SRS‐A antagonist FPL 55712. Arylsulfatase B, which is an enzyme that inactivates SRS‐A, also abolished the contractions induced by tartrazine. Contractions induced by carbacholine, histamine, egg albumin and arachidonic acid were slightly reduced by indomethacin and tartrazine. Tartrazine like indomethacin inhibited the generation of thromboxanes from human platelets. We suggest that SRS‐A plays an important role in the immediate hypersensitivity reactions of tartrazine and indomethacin in guinea pig

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01595.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Acute toxicity and organ distribution of cadmium was investigated in mice exposed to 1)single subcutaneousdoses of109Cd‐labelled cadmium (3.2 mg (0.028 mmol)/kg b.wt.) alone or in combination with nitrilotriacetic acid, NTA (32 mg (0.167 mmol)/kg b.wt.) or sodium tripolyphosphate, STPP (32 mg (0.087 mmol)/kg b.wt.) and 2)single oraldoses of cadmium (60 mg (0.53 mmol)/kg b.wt.) alone or together with NTA (600 mg (3.14 mmol)/kg b.wt.) or STPP (600 mg (1.63 mmol)/kg b.wt.) Whole‐body retention of radiolabelled cadmium as well as mortality was registered in all groups during 20–21 days. Five hours after exposure, 3–4 mice in each group were killed and cadmium distribution among proteins in liver and kidney studied by gel chromatography on a G‐75 Sephadex column. Organ concentration of cadmium was also determined at sacrifice of all other mice after an observation time of 20–21 days. A markedly increased mortality was observed during the first 24 hours after subcutaneous exposure to Cd+NTA (70%) or Cd + STPP (40%) compared to Cd alone (0%). On the contrary, no mortality was seen after oral exposure to Cd + STPP while oral exposure to Cd alone or with NTA resulted in a mortality of about 45% during the same observation time. Five hours after subcutaneous exposure, liver cadmium concentrations were equal in all mice and bound mainly to a low molecular weight protein (probably metallothionein). In kidney, concentrations were about twice as high in mice given Cd + NTA or Cd + STPP compared to mice given Cd alone. More cadmium was transferred to the kidneys in the presence of chelating agents. This was further supported by the decreased liver/kidney cadmium concentration ratio between 5 hours and 21 days. The increased mortality in mice given Cd + NTA or Cd + STPP may be due to an initially high accumulation of cadmium in liver, which may exceed the upper limit for metallothionein synthesis, whereby toxic damage of the hepatic cells and leakage of cadmium from the liver would occur. Five hours after oral exposure, cadmium retention in organs of mice given Cd+STPP was 4–6 times lower than in mice given Cd alone, while mice given Cd+NTA had slightly higher organ concentrations. The binding of more cadmium to metallothionein in liver of Cd + STPP‐exposed mice 5 hours after exposure, may be due to the lower accumulation of cadmium in these mice compared to those given Cd alone or Cd+NTA, where cadmium was bound mainly to high molecular proteins in the liver. After 20 days, mice given Cd+STPP has slightly higher body and organ retention of cadmium compared to mice given Cd alone. This may be due to a binding of cadmium to metallothione in these mice which is known to prolong the retention time of ca

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01596.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effects of 3‐methylcholanthrene (MC) pretreatment on metabolism and mutagenic activation of dimethylnitrosamine (DMN) were studied with liver subfractions from two strains of mice differing genetically with respect to aromatic hydrocarbon responsiveness. Both mutagenic activation and DMN N‐demethylase activity segregated with aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity as a dominant trait in appropriate crosses between C57BL/6J (AhbAhb) and DBA/2J (AhdAhd) mice. DMN metabolism and mutagenicity were increased by MC‐pretreatment in responsiveAhbAhbandAhbAhdmice, but not in non‐responsiveAhdAhdmice. This indicates the involvement of theAhlocus in the genetic regulation of these activities in mice. Deuteration of DMN reduced mutagenicity and DMN N‐demethylase activity by approximately 90 and 50 percent, res

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01597.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:LS 1727, a nitrosocarbamate of 19‐nortestosterone, was active against lymphoid, antimetabolite‐sensitive, cell linesin vitroespecially L1210 and Ehrlich ascites tumour lines. It was less effective against alkylating agent‐sensitive lines such as the Walker 256 carcinosarcoma. These results suggested a possible antimetabolite mode of action but LS 1727 had no effect on deoxy‐ or ribonucleotide pool sizes in L1210 cells. Studies on macromolecular synthesis showed an early inhibition of DNA synthesis whilst RNA and protein synthesis continued for 24–48 hours. This was reminiscent of a classic alkylating agent‐like effect.In vivostudies with specific alkylating agent‐sensitive, or antimetabolite‐sensitive tumours showed no antitumour activity although significant inhibition of Ehrlich ascites tumour cell growth was observed at high doses.In vitrocytotoxicity studies showed LS 1727 to be inactivated in the presence of mouse, rat and dog liver supernatants. This would explain the poor antitumour effectsin vivocompared with thein vitroobservations. Because LS 1727 is a nitrosocarbamate its possible mutagenic activity was investigated. LS 1727 was highly mutagenic but this property was also lost in the presence of a rat liver microsomal fraction. Although an effective cytotoxic agentin vitroLS 1727 is only effectivein viv

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01598.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effect of adrenalectomy and hypophysectomy on 5‐HT uptake by rat platelets and hypothalamic synaptosomes taken from the same animal was studied. The experiments were performed 1–2 weeks after the operations or the shamoperations. After adrenalectomy a significant decrease of 25% in 5‐HT uptake by platelets was noted. In synaptosomes there was a similar trend, but the decrease was not significant. After hypophysectomy a significant 25% decrease in 5‐HT uptake was observed both in platelets and in synaptosomes. These results suggest that corticosteroid hormones might mediate adaptive changes of 5‐HT uptake both in synaptosomes and in blood platelets. Blood platelets have been used as a peripheral model of serotoninergic nerve terminal in studies concerning physiology of monoamines systems, but the present results suggest that also in some pathological conditions changes in platelet biochemistry could reflect those in the CNS

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01599.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Urinary excretion of electrolytes and uric acid was investigated in six healthy subjects during repeated oral administration of 100 mg hydroflumethiazide (HFT) daily for seven days, and related to urinary thiazide excretion. Mean 24 hr‐urinary excretion of sodium and chloride increased 100% (P<0.02) after the first HFT‐dose, whereas 24 hr‐excretion values were at control level after the fourth and seventh doses. Mean 24 hr‐urinary excretion of potassium was increased by 31% after the first HFT‐dose (P<0.05) and by 47% after the fourth dose (P<0.05). After HFT was discontinued, mean urinary excretion rates of sodium and chloride dropped to 30% and that of potassium to 70% of control. In the state of fluid deficiency and elevated aldosterone concentration, there was a significant positive correlation between log excretion rate of HFT and excretion rate of sodium (r=0.68, P<0.002) calculated from excretion data 0–6, 6–12, and 12–14 hrs after the seventh dose. After the first dose of HFT, sodium excretion was also significantly correlated to log excretion rate of HFT (r=0.86, P<0.001) but was probably influenced by other factors as well. Mean serum concentration of uric acid increased significantly, but mean 24 hr‐urinary excretion of uric acid was constant dur

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01600.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Slices of rat lung were incubated with tritiated 5‐hydroxytryptamine and the tissue uptake of tritium was studied after separating the free and bound radioactivity by filtration on glass fiber filters. At 37° a rapid uptake occured during the first 10 min. After that time the uptake was less marked but it was still present after 60 min. The uptake was moderately potentiated by the MAO inhibitor iproniazid (3 μM) after 30–60 min. incubation. The 5‐hydroxytryptamine uptake was inhibited by some uptake inhibitors, their order of potency beeing: clomipramine>imipramine ≥ nortriptyline ≥ cocaine ≥ desipramine>maprotiline. At 0° the uptake of 5‐hydroxytryptamine was negligible. Non‐linear regression analysis of uptake data indicated that 5‐hydroxytryptamine was taken up by two different mechanisms. One of the uptake processes was saturated by high concentrations of 5‐hydroxytryptamine and showed an apparent Kmof 8×10−7M. The other uptake was linearly related to the 5‐hydroxytryptamine concentration and could not be saturated even by concentration

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01601.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY