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Biomedical subjects

M S Rose

Publications and source records attributed to M S Rose.

At least 73 records · Page 4Linked to original sources
PubMed1981

Factors affecting the efflux of paraquat from rat lung slices.

In an attempt to reduce the toxicity of paraquat several compounds were examined for their ability to increase the rate of efflux of paraquat from the lung. The compounds were selected because they were known, from in vitro studies, to reduce the accumulation of paraquat into the lung. Histamine (100 MicroM), promethazine (100 microM), putrescine (100 microM), bromthymol blue (300 microM) and the metabolic inhibitors iodoacetate (1 mM), rotenone (100 microM) and KCN (1 mM) have been shown to reduce the accumulation of paraquat into rat lung slices, as did the incubation of slices under nitrogen. The efflux of paraquat from lung slices prepared from rats dosed intravenously with paraquat was biphasic, having a very fast component and a slow component. The slow component was first order and was characterised by a t1/2 of 17 h. This half life is similar to that seen in vivo (24 h) following intravenous dosing. When lung slices prepared from rats dosed intravenously with paraquat were incubated in the presence of iodoacetate (1 mM) or under nitrogen, the half life of paraquat in the slices was reduced to approximately 3 h. In the presence of rotenone (100 microM) it was reduced to approximately 9 h. Histamine (100 microM) and promethazine (100 microM) did not affect the efflux of paraquat from lung slices. Bromthymol blue, a dye which forms "ion pair" complexes with paraquat, also significantly increased the efflux of paraquat from lung slices. The effect of bromthymol blue, however, decreased with time and thus paraquat efflux in the presence of bromthymol blue did not obey first order kinetics. In order to measure cellular viability of lung slices, oxygen consumption, glucose oxidation and the rate of the efflux of protein from the slices into the incubation medium were determined. Iodoacetate (1 mM) and rotenone (100 mM) almost abolished oxygen consumption and glucose oxidation whereas these activities were inhibited to a lesser extent by bromthymol blue (300 microM) (18% and 30%, respectively). During the first 30 min of incubation in the presence of KCN (1 mM) oxygen consumption was almost abolished but between 30 min and 4 h returned to control levels. The effect of KCN could therefore be divided into 2 phases. Over 4 h incubation glucose oxidation was inhibited by 36%. Iodoacetate (1 mM) and incubation under nitrogen caused the most pronounced increases in the rate of protein efflux from slices. KCN (1 mM) and rotenone (100 microM) also increased the rate of protein efflux but to a lesser extent. We have therefore suggested that the effect of KCN (1 mM) on cellular viability, while severe, may be less than that of iodoacetate (1 mM) or incubation under nitrogen...

Animals↗
PubMed1981

Malignant lymphomas: results and observations from St George's Hospital.

With both Hodgkin's and non-Hodgkin's lymphoma, the results documented compared well with reference series. Hence the advantages of a modest clinic need not be at the cost of recovery or of survival. A major factor attenuating the scale of therapy in Hodgkin's disease is the risk of inducing second malignancies. Four such complications have been observed amongst 27 patients with Hodgkin's disease. Amongst the patients with non-Hodgkin's lymphoma better results were noted than the designation 'poor prognosis histology' had led the authors to expect. These findings suggest that the concept of histologically based prognosis may be over-subscribed and that contemporary therapeutic strategies can be extremely effective in this group.

Adolescent↗
PubMed1980

The use of biochemical methods for detecting changes in cell population of rat bone marrow.

The in vitro incorporation of 14C-glycine into haem, and 35S-sulphate into macromolecules have been investigated as biochemical measurements with the potential to reflect the proportion of certain erythroid and myeloid cells within rat bone marrow. Erythroid hyperplasia caused an increase of haem synthesis and a concomitant decrease in 35S-sulphate incorporation. Erythroid hypoplasia reduced haem synthesis and increased 35S-sulphate incorporation. The measures of haem synthesis and 35S-sulphate incorporation thus provide useful tools for detecting specific changes in cell populations in rat bone marrow suspensions.

Animals↗
PubMed1979

The toxicity and renal handling of paraquat in cynomolgus monkeys.

The acute intravenous and oral toxicity of single doses of paraquat dichloride was studied in the cynomolgus monkey. Renal handling and effects upon renal function were also investigated following an oral dose of [14C]paraquat. Clinical signs consisted of vomiting, anorexia and dyspnoea. By 48 h all animals showed signs of acute renal failure with oliguria, high plasma urea and SGPT levels and metabolic acidosis. Animals dosed orally showed similar, though less severe, signs to those dosed intravenously. The oral LD50 was approx. 70 mg paraquat cation/kg. Following an oral dose plasma levels peaked by 2 h, but were constant from 12 h to 24 h. Paraquat clearance was high initially and exceeded the creatinine and urea clearance, but fell off markedly after 14 h as renal failure developed. By 18 h urine production had ceased. It is concluded that acute renal failure and acute pulmonary damage are the main causes of death, with interstitial pulmonary fibrosis being a factor in animals surviving the acute phase.

Absorption↗
PubMed1974

Effective treatment for paraquat poisoning in rats and its relevance to treatment of paraquat poisoning in man.

After oral administration of a lethal dose of paraquat to rats the plasma concentration remained relatively constant over four to 30 hours and was related to the paraquat content of the small intestine over the first 16 hours. During the first 30 hours the concentration of paraquat in the lung rose progressively above that of the plasma to levels which are known to cause pulmonary damage. A treatment has been devised which prevents the absorption of paraquat into the plasma and prevents accumulation of paraquat in the lung. This treatment consists of a stomach was followed by four administrations of bentonite plus purgatives at two- to three-hour intervals. Even when treatment was delayed until 10 hours after administration of paraquat 80% survival was obtained. The relevance of this treatment to paraquat poisoning in man is discussed in the light of the finding that slices of human lung accumulate paraquat in the same way as those of rat lung.

Absorption↗