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Biomedical subjects

J Alexander

Publications and source records attributed to J Alexander.

At least 541 records · Page 30Linked to original sources
PubMed1982

Organ distribution and cellular uptake of methyl mercury in the rat as influenced by the intra- and extracellular glutathione concentration.

Intravenous administration of CH3HgCl (4 mumol/Kg) premixed with glutathione or cysteine (8 mumole/kg) to female rats caused a rapid uptake of mercury in the kidney and a depressed content in the liver and blood as compared to CH3HgCl given alone. GSH depletion in the tissues, produced by injection of diethylmaleate, DEM (3.9 mmole/kg) did not influence the kidney uptake of mercury from administered (CH3Hg+-GSH, whereas the uptake of injected CH3HgCl was depressed. Both GSH and cysteine (8 mumole/kg) promoted the biliary excretion of methyl mercury. In suspensions of rat erythrocytes and isolated hepatocytes, additions of GSH reduced the cellular uptake of CH3Hg+ from the medium, whereas this was increased in the hepatocytes by adding cysteine or methionine. Cysteine addition slightly reduced the uptake of CH3Hg+ in the erythrocytes. GSH-depletion as obtained by DEM pretreatment of the cells, reduced the Ch3Hg+ uptake into hepatocytes by 40%, in contrast to only a negligible effect on the erythrocytes. Our results support previous reports that a physiological CH3Hg+-GSH-complexation takes place intracellularly, at least in liver cells. Our results are furthermore consistent with the assumption that biliary excreted CH3Hg+-GSH, which can be reabsorbed, only to a limited extent is taken up by the liver, whereas this GSH-complexation and reabsorption is of importance for the Ch3Hg+-uptake in the kidneys.

Animals↗
PubMed1982

The effect of chelating agents on vanadium distribution in the rat body and on uptake by human erythrocytes.

Pentavalent vanadium (V5) as Na48VO3 was given i.p. to male Wistar rats at a dose of 5 mumol/kg in order to study its organ distribution pattern. Two days after injection, kidneys reached a V level of about 28 nmol/g wet weight, followed in decreasing order by spleen, liver, bone, blood plasma, testis, lung, erythrocytes and brain in control rats. A similar distribution pattern was seen after injection of tetravalent vanadium (V4) given as 48VOSO4. Two chelators, desferrioxamine B (Desferal) or Ca-Na3-diethylene triamine pentaacetic acid (DTPA), were given i.p. 24 h after the vanadium injections to different groups of rats at two dosage levels, 30 and 100 mumol/kg. Desferal (30 mumol/kg) reduced the vanadium content of the kidney by 17%, of the liver by 0%, and of the lung by 7%. The corresponding figures for the effect of DTPA (30 mumol/kg) were 7%, plus 15%, and 0%, respectively. At 100 mumol/kg, Desferal reduced the same organ levels by 20%, 26%, and 25%, respectively, and DTPA by 9%, 18%, and 25%, respectively. Both chelators raised faecal excretion at the low level, and both urinary and faecal excretion at the high level. Spleen and bone seemed to bind vanadium to a higher degree than the other organs under examination. Human erythrocytes, when incubated with 48VOSO4 (V4) or Na48VO3 (V5), were found to accumulate nearly the double amount of V5 as compared to V4. Glutathione (GSH) which is the main reducing substance within the erythrocytes, reduced the uptake of V5 to the V4 level when incubated together with GSH before addition to the cell suspension. Pretreating the erythrocytes with diethyl-maleate (DEM) which blocks the reducing SH groups of intracellular GSH, also reduced the uptake of V5. This may indicate a GSH dependent reduction of V5 to V4 within the erythrocytes. Four chelators, among them Desferal and DTPA, were found to reduce the cellbound amount of vanadium, either by extracting vanadium as V4, or by inhibiting uptake by the red blood cells.

Animals↗
PubMed1982

Radionuclide angiographic exercise left ventricular performance in chronic aortic regurgitation: relationship to resting echographic ventricular dimensions and systolic wall stress index.

Forty-five patients with chronic aortic regurgitation (AR) underwent first-pass radionuclide angiocardiography (RNA) at rest and during upright bicycle exercise, as well as M-mode echocardiography at rest. Abnormal left ventricular (LV) exercise reserve, defined by the absolute change in ejection fraction (EF), was present in 16 of 45 patients (36%). Seven of ten patients with abnormal resting EF (less than 50%) and three of seven symptomatic patients had normal LV exercise responses. Patients with normal LV exercise reserve by RNA had LV dimensions by echo at end diastole (5.9 +/- 0.2 vs 6.5 +/- 0.3 cm, p = NS) and end systole (3.9 +/- 0.2 vs 4.4 +/- 0.3 cm, p = NS) comparable to those in patients wht abnormal LV exercise reserve. However, the mean corrected LV end-diastolic (LVED) radius/wall thickness ratio was significantly greater in AR patients with abnormal LV exercise reserve than in those with normal LV exercise reserve (395 +/- 15 vs 315 +/- 16, p less than 0.01). There data suggest that resting echocardiographic LV dimensions as well as the corrected echo LVED radius/wall thickness ratio have a variable relationship to RNA LV exercise performance in patients with chronic AR.

Adolescent↗
PubMed1982

A radioattenuated Leishmania major vaccine markedly increases the resistance of CBA mice to subsequent infection with Leishmania mexicana mexicana.

Vaccinating CBA mice with radioattenuated Leishmania major amastigotes but not with radioattenuated L. mexicana mexicana amastigotes rendered them highly resistant to subsequent infection with L. m. mexicana. Unvaccinated CBA mice were highly susceptible to infection with L. m. mexicana producing rapidly growing non-ulcerating cutaneous lesions. Two manifestations of resistance were induced in vaccinated animals depending on the timing of the challenge infection: no lesions appeared at the site of subcutaneous challenge in animals vaccinated four or more weeks previously, while lesions grew rapidly but ulcerated and healed in animals vaccinated less than 3 weeks beforehand. L. major amastigotes were found to be markedly more resistant to gamma irradiation than L. m. mexicana amastigotes both as measured by their ability to infect susceptible strains of mice and to transform and multiply as promastigotes in NNN medium.

Animals↗
PubMed1982

Uptake of chromium by rat liver mitochondria.

Isolated rat liver mitochondria rapidly accumulate chromate (1.2 microM 51CrO4(2-)) to about 0.25-0.30 nmol Cr/mg protein. The relative uptake decreases with increasing chromate doses. Chromate uptake decreases when pH is raised from 7.0 to 7.5.N-ethylmaleimide (0.25 mM) and butylmalonate (5 mM) inhibit chromate uptake to 70% and 30% of control values, respectively, whereas mersalyl (40 nmol/mg protein) causes an inhibition of greater than 95%. Both sulphate and phosphate decrease mitochondrial chromate uptake, the former being more effective in lower doses (5 mM). These results indicate that transport of chromate is mediated both on the dicarboxylate and the phosphate carrier. The extensive mitochondrial chromium accumulation can be explained by trapping of chromium, probably by reduction of chromate to the trivalent form, within the mitochondria. Release of chromium after chromate loading was seen after 15 min. Added after chromate loading, mersalyl partly prevents this release. Trivalent chromium as 51CrCl3 is taken up to a much lower degree than hexavalent chromium as 51CrO4(2-). The presence of glutathione (5 mM) reduces the uptake both of 51Cr-III and 51Cr-VI, indicating extramitochondrial reduction of Cr-VI to Cr-III and subsequent binding to GSH.

Animals↗
PubMed1982

Serum selenium levels in liver diseases.

A possible pathogenetic role of selenium deficiency in alcoholic cirrhosis of the liver has previously been discussed. In the present study serum selenium was analyzed in 5 groups of liver diseases. The method used for selenium determination was electrothermal atomic absorption, after thermal stabilization of selenium compounds by addition of nickel nitrate. The selenium level of a reference group of healthy Norwegian adults (n = 40) was 1.53 +/- 0.25 mumol/l. The serum concentrations of selenium in patients suffering from alcoholic cirrhosis, chronic active hepatitis and chronic persistent hepatitis were lowered to 40-80 per cent of those of the reference group. In alcoholic cirrhosis and chronic active hepatitis the decreased serum selenium concentrations were significantly correlated to decreased levels of albumin and prealbumin.

Hepatitis, Chronic↗
PubMed1982

Uptake of 51Cr-chromate by human erythrocytes-a role of glutathione.

Hexavalent chromium (Cr-VI), as Na2CrO4 in an aqueous solution, was reduced rapidly ot the trivalent form (Cr-III) in the presence of glutathione, GSH (0.3-3.0 mM). Such GSH-dependent reduction Cr-VI can take place in the cytosolic space of Cr-VI-exposed cells, since GSH is found in reactive concentrations in this compartment. The reduction makes chromium essentially impermeable through the cell membrane, explaining the observation that Cr-VI, when added to red cell suspensions, is bound quantitatively intracellularly after a few hours. Diethylmaleate conjugation of the SH-group of the intracellular GSH preventing the oxidation to GSSG, lowered the chromium-uptake significantly, showing that reduced GSH plays a role for the chromium binding. In healthy red cells chromium is partially bound to haemoglobin and partially to small molecular weight substances, probably in the trivalent form. This intracellular chromium cannot be removed to the extracellular space by addition of chelating agents as long as the cell membrane is intact.

Chromates↗
PubMed1982

Biliary excretion of chromium in the rat: a role of glutathione.

The relative amount of chromium excreted in rat bile after injection of Cr-III is much less than after injection of Cr-VI, about 0.1% and from 6-8% during 5 hours respectively, for corresponding dose levels. The liver to bile ratio was 50-100 for Cr-III injection, for Cr-VI the ratio was 2-3. With doses up to 18 mumol Cr/kg, only Cr-III was found in bile even after injection of Cr-VI. Glutathione depletion of the liver with cyclohexene oxide decreased chromium excretion in bile. Such treatment also decreased the reduction of Cr-VI to Cr-III in the liver cell as only Cr-VI was found in bile. A different distribution of Cr-III in the liver dependent on whether derived from Cr-VI or taken up by the liver as such must be assumed. Taking into account the usual low penetration of biological membranes by Cr-III, a possible active transport mechanism or a specific diffusable Cr-III compound must be postulated.

Animals↗
PubMed1982

Attitudes of patients toward diagnostic tests. The case of the upper gastrointestinal series roentgenogram.

As part of a study of the clinical value of the upper gastrointestinal roentgenogram series (UGI), we assessed patient attitudes toward the UGI and toward tests in general. We surveyed 483 people undergoing 495 outpatient UGIs at three different hospitals. The majority of the patients wanted to have the UGI, were reassured by the test, thought it helped their physicians, would undergo it again for the same problem, and would have requested the test had their physicians not ordered it. Factors that were associated with favorable attitudes toward tests included male sex, older age, having been told the results of the UGI, improvement in symptoms, and lower educational achievement. We conclude that patients place a high value on certain diagnostic tests and that these attitudes may be associated with sociodemographic factors, patient-physician communication and patient symptom status.

Adult↗
PubMed1982

Treatment of mercuric chloride poisoning with dimercaptosuccinic acid and diuretics: preliminary studies.

The distribution and excretion of mercury were studied in mice given a single injection of HgCl2 with or without chelation treatment. DMS (2,3-dimercaptosuccinic acid) given intravenously (0.5 mmol SH/kg) to mice 24 h after the mercury injection reduced the kidney Hg level significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. The effectivity of DMS to remove Hg from kidneys was comparable to that of BAL-sulph (2,3-dimercaptopropane-1-sulfonate), irrespective of whether these chelating agents were given orally or intravenously. Immediate chelation treatment with DMS or mercaptodextran reduced the renal Hg level to about 50% of control levels, as measured 3 d after the treatment. Combination of DMS with immediate intraperitoneal treatment with spironolactone was even more effective in reducing the renal levels, and acted both by increasing the fecal and urinary excretion. The DMS treatment, as well as DMS + spironolactone in combination, could protect against kidney damage following injection of 30 mumol HgCl2/kg. Such treatment was essentially nontoxic.

Animals↗
PubMed1981

Effect of thiocarbamate derivatives on copper, zinc, and mercury distribution in rats and mice.

Oral treatment of rats with tetramethylthiuram disulphide (TMTDS), 0.1% mixed in the food (corresponding to 20--30 mumol daily) for one week, increased the brain levels of endogenous copper and zinc to 120% and 170%, respectively, of the control levels. Mice injected with HgCl2 (2.5 mumol/kg) were used to study further the effect of DDC (diethyldithiocarbamate), disulfiram, TMTDS or CS2 on heavy metal distribution. The brain levels of Hg were significantly increased in mice given DDC or TMTDS. Disulfiram and CS2 increased the brain levels marginally. Pregnant rats exposed to HgCl2 (0.5 mumol/kg) were also included in the studies. Treatment with DDC (0.5 mmol/kg) immediately after the mercury injection, increased the maternal brain concentration of mercury considerably, as measured after 24 and 78 h. The kidney levels were also increased. In the foetuses, the brain and liver levels were transiently increased after treatment with diethyldithiocarbamate. The observations support the hypothesis that the neurotoxicity of diethyldithiocarbamate and other thiocarbamates may be related to changes in heavy metal metabolism.

Animals↗
PubMed1981

[Acute myocardial infarction: epidemiologic study of the proportion of patients who die before reaching a hospital].

In the treatment of acute myocardial infarction, the first few hours following the onset of symptoms are often decisive as to the outcome. However, many patients die before reaching a hospital. We tried to estimate this proportion for one year for the canton of Tessin by studying hospital data and official death certificates. Such an estimation is most important for the measurement of the incidence of an often rapidly fatal disease like acute myocardial infarction, as well as for the evaluation of forms of emergency transport and care in our health system.

Female↗
PubMed1981

Evaluation of methyl mercury chelating agents using red blood cells and isolated hepatocytes.

The relative efficacy of thiol-containing mercurial scavengers was assayed by using cellular suspensions of erythrocytes or isolated hepatocytes. The blood cells incubated in a buffer (pH 7.4) containing 1 mM glucose (10% hematocrit) were exposed to 5 microM methyl mercuric chloride. In the absence of extracellular thiols the red blood cells took up more than 90% of methyl mercury from the surrounding medium during 5--10 min. This uptake was almost completely inhibited by dimercaptosuccinic acid (DMSA) (1 mM) and the same chelant could rapidly remove 80% of the mercury from 'pre-loaded' erythrocytes. Hepatocytes prepared according to the method of Seglen [11] in a suspension of 10(6) cells/ml in a buffer containing 5 mM glucose and 5 mg/ml of bovine serum albumin were also exposed to methyl mercuric chloride (4 microM). Almost 50% of the mercurial was taken up by the cells slowly during the incubation period of 240 min. DMSA (1 mM) almost completely blocked the methyl mercury binding by the hepatocytes. 2-Mercaptopropionylglycin (Thiola) or mercaptosuccinic acid (MSA) was almost as effective mercurial scavengers as DMSA in hepatocytes and in red blood cells. Diethyldithiocarbamate (DDC) and dimercaptopropanol (BAL) were considerably less effective than DMSA to inhibit the mercurial binding to hepatocytes. Experiments in vivo have shown that DMSA is a better mercurial chelator than Thiola or MSA, whereas DDC and BAL may both be considered to be inapplicable in methyl mercury poisonings. Our cellular assay provides preliminary information of the efficiency of chelating thiols and may serve as a useful first approximation when planning further experiments.

Adult↗