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Biomedical subjects

A Hodgson

Publications and source records attributed to A Hodgson.

At least 55 records · Page 3Linked to original sources

The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.

Administration, Inhalation↗

Factors affecting the in vitro dissolution of cobalt oxide.

In a recent interspecies comparison of the lung clearance of cobalt oxide (57Co3O4), differences of up to 4-fold were found in the translocation rates of 57Co to blood between seven different animal species, including man. This study investigated some factors that could influence the dissolution of this material in vitro. The effect of bicarbonate and citrate concentrations (over physiological ranges) and medium pH on in vitro dissolution of 57Co from 57Co3O4 particles was measured in a simple noncellular system. pH levels of 4.5, 6.1, and 7.2 were used to correspond to those in the alveolar macrophage lysosome, its cytoplasm, and the extracellular lung fluid. Measurements of the fractional dissolution rate were made weekly for 3 months. pH had the greatest effect on dissolution rates, with particles suspended in the lowest pH medium (4.5) dissolving at a significantly faster rate than at higher pH values. Increasing citrate concentrations resulted in slightly higher dissolution rates, but there was no effect of bicarbonate concentration. There was no evidence of synergism between the factors studied.

Antacids↗

Effect of bronchopulmonary lavage on lung retention and clearance of particulate material in hamsters.

Hamsters were exposed to an aerosol of fused aluminosilicate particles (FAP) labeled with 57Co. Three groups of animals were given bronchopulmonary lavage, beginning at either 1 week, 1 month, or 6 months after exposure. Each treated group was lavaged eight times over a period of 25 days. Each lavage involved 10 saline washes of the lungs. For each group, about 60-70% of the body content of 57Co at the start of lavage treatment was removed; nearly half of this was recovered in the first two lavages. A positive correlation was demonstrated between the macrophage content and 57Co activity of the washings. The subsequent fractional clearance rate of 57Co from lavaged animals was not significantly different from that in a group of untreated control animals.

Aerosols↗

Involvement of cellular division cycle in the susceptibility of Escherichia coli to cold- and osmotic-shock.

Susceptibility of Escherichia coli to cold-shock, osmotic-shock and cold-osmotic-shock has been evaluated throughout the cellular division cycle for a variety of generation time. Two periods of sensitisation were detected. The first of these was towards cold-shock which occurred 60 min prior to cell division and might correspond to initiation of DNA replication. The second period of sensitisation was towards both cold-, osmotic- and cold-osmotic-shock and occurred immediately prior to and during cell division. Patterns and extents of sensitisation towards each of these three stresses during the second period were suggestive of a common sensitising event associated with constriction of the cell and separation.

Cell Cycle↗

The efficacy of DFO-HOPO, DTPA-DX and DTPA for enhancing the excretion of plutonium and ameriicum from the rat.

A hydroxypridinone derivative of desferrioxamine (Na-DFO-HOPO), a dihydroxamic derivative of diethylenetriaminepenta-acetic acid (ZnNa-DTPA-DX), and DTPA (CaNa3- and ZnNa3-DTPA) were tested at dosages of 30 mumol kg-1 for their ability to remove 238Pu or 241Am from rats after their intravenous injection as citrate or inhalation as nitrate. The most effective treatment regimen for injected Pu was the repeated administration of DFO-HOPO; by 7 days the body content was reduced to 8% of that in untreated animals. Repeated dosages of 3 mumol kg-1 DFO-HOPO were as effective as those of 30 mumol kg-1 DTPA. After inhalation of Pu nitrate, repeated treatment with DTPA, DTPA-DX or DFO-HOPO reduced the body content by 7 days to, respectively, 10, 15 and 31% of those in untreated animals. After inhalation of Am, DTPA-DX and DTPA were equally effective, the body contents being reduced to 7% of control values with repeated treatment. Injection of DFO-HOPO was ineffective for enhancing the elimination of inhaled or injected Am. The results confirm the strategy of examining the use of siderophore analogues for the decorporation of Pu or Am. However, at present DTPA should remain the agent of choice, particularly after inhalation.

Administration, Inhalation↗

Double-blind comparative multicentre study of fluvoxamine and mianserin in the treatment of major depressive episode in elderly people.

This is a multicentre double-blind study of fluvoxamine versus mianserin in the treatment of major depressive episode in patients over 65 years of age. Fifty-seven patients received either fluvoxamine (100-200 mg daily) or mianserin (40-80 mg daily). There was no statistically significant difference in improvement between the 2 treatment groups as measured by the Montgomery-Asberg Depression Rating Scale. Eleven patients (7 in the fluvoxamine group and 4 in the mianserin group) discontinued treatment because of intolerance. No statistically significant differences were seen in biological parameters with either drug. Both drugs improved the symptoms of depression though the overall response rate was not outstanding. The side effects profile for the fluvoxamine was contrary to previous studies in that frequent nausea and vomiting were not seen.

Aged↗

The efficacy of DTPA treatment after deposition of thorium nitrate in the rat lung.

The efficacy of CaDTPA and ZnDTPA, the chelating agents of choice for several actinide elements, have been evaluated after the deposition of thorium in the rat lung in widely different amounts. The results showed that: 1. When the initial mass concentration of thorium simulated human exposure to four times the annual limits on intake for 232Th, the prompt (300 or 1000 mumol kg-1 body weight at 0.02 d) or repeated (30 or 300 mumol kg-1 body weight at 0.02, 0.25, 1,2,3 d) administration of CaDTPA were at best only moderately successful for enhancing the elimination of thorium. By 7 d after exposure, the body contents of thorium were, respectively, about 74%, 65%, 90% and 74% of those present in untreated animals. 2. When the mass concentration simulated 1.7 x 10(-3) times the annual limits on intake for 232Th, the efficacy of treatment was not increased appreciably despite the substantial reduction in mass. After the repeated administration of CaDTPA at doses of 30 and 300 mumol kg-1 using the protocol above, the body contents of thorium by 7 d were, respectively, 69% and 51% of those in untreated animals. 3. Under comparable conditions, the efficacy of ZnDTPA was less than CaDTPA. The results suggest that more effective chelating agents are needed for the treatment of workers exposed to water soluble thorium compounds.

Administration, Inhalation↗

A new small animal inhalation facility: design and performance.

A new inhalation facility is described which allows any combination of up to 72 rodents ranging in size from the mouse to the guinea pig to be exposed simultaneously. Typically for aerosols of MMD 1.5 microns the initial lung deposit in the rat is 0.05 to 0.07% of the total amount of material used and the coefficient of variation between animals is 15 to 20%.

Administration, Inhalation↗

The metabolic behaviour of uranium octoxide bearing residues after their deposition in the rat lung: the implications for occupational exposure.

This paper describes the metabolic behaviour in rats of uranium inhaled as a U3O8 bearing residue. The biokinetic behaviour of uranium in workers has been predicted by combining the transfer rates to blood in rats with mucociliary clearance rates obtained from human volunteers exposed to other aerosols. It is concluded that chest monitoring will be of value for assessing acute and chronic intakes of the residue below the proposed annual limit (6 x 10(3) Bq) whilst urinary excretion data should be interpreted with caution.

Air Pollutants, Occupational↗

The efficacies of pure LICAM(C) and DTPA for enhancing the elimination of plutonium-238 and americium-241 from rats after their inhalation as nitrate.

After the inhalation of 238Pu and 241Am as nitrate, the repeated administration of DTPA is far superior to that of LICAM(C) for enhancing their elimination from the body. The therapeutic efficacies of these chelating agents are however similar after intravenous injection of 238Pu as citrate. It is concluded that DTPA should remain the agent of choice for treating persons contaminated internally with transportable forms of these actinides.

Administration, Inhalation↗

The efficacies of pure LICAM(C) and DTPA on the retention of plutonium-238 and americium-241 in rats after their inhalation as nitrate and intravenous injection as citrate.

The pure carboxylated catechoyl amide LICAM(C) and the calcium and zinc salts of diethylenetriaminepenta-acetic acid (DTPA), were tested for efficacy for removing 238Pu and 241Am from rats after inhalation of the nitrate or intravenous injection of the citrate. The results were compared with the efficacy of methylated LICAM(C) used in previous experiments. It was shown that: (1) after inhalation of 238Pu nitrate, DTPA was far superior to pure LICAM(C); (2) after intravenous injection of 238Pu citrate, the infusion of DTPA plus LICAM(C) was only marginally more effective than DTPA alone; and (3) after inhalation or intravenous injection of 238Pu plus 241Am, the efficacy of pure LICAM(C) was only marginally more effective than the methylated form and neither form was effective for the decorporation of 241Am. It was concluded that DTPA, at present, remains the chelating agent of choice for treating persons accidentally contaminated with transportable forms of Pu and Am.

Aerosols↗

The metabolism of ceramic and non-ceramic forms of uranium dioxide after deposition in the rat lung.

Ceramic and non-ceramic forms of uranium dioxide, produced industrially, were administered to rats either by inhalation or as an aqueous suspension which was injected directly into the pulmonary region of the lungs. The results showed that: 1 both materials should be assigned to inhalation class Y as defined by the International Commission on Radiological Protection; 2 whilst the translocation of uranium to the blood for the non-ceramic UO2 was about twice that obtained for the ceramic form, the two dioxides were unlikely to be differentiated on the basis of their lung retention kinetics; 3 the distribution of uranium amongst body tissues and the relationship between systemic content and cumulative urinary excretion indicated that it was transported in the hexavalent form; 4 in addition to air sampling procedures, lung radioactivity counting measurements could be used to advantage for assessing occupational exposures; 5 the exposure limits should be based on radiation dose rather than chemical toxicity.

Administration, Inhalation↗

Premenstrual syndrome. A double-blind cross-over study of treatment with dydrogesterone and placebo.

A double-blind, cross-over, placebo-controlled study of dydrogesterone (10 mg b.d.) in the treatment of premenstrual syndrome is described. Two groups of women were studied: secondarily referred hospital clinic patients, and self-referred patients. Only one-third of patients screened completed the study. All patients showed significant improvements in symptom scores during the course of the study, the only significant difference between placebo- and dydrogesterone-treated patients being an increase in frequency of breast tenderness and a decrease in pain with menstrual bleeding in the latter.

Adult↗

The use of microinjected colloidal gold and immunocytochemistry to localise pressor sites in the rostral medulla oblongata of the rat.

A new technique for localising the centre of sites of microinjection of drugs in the brain using the silver intensification of colloidal gold is described. The technique is compatible with immunocytochemistry and in this study was used in Wistar-Kyoto rats to investigate the relationship between the location of phenylethanolamine-N-methyltransferase-like immunoreactive (PNMT-LI) cell bodies in the medulla and the precise sites where microinjection of L-glutamate elicited pressor responses. Colloidal gold provided a simple technique for localising the centre of sites of microinjection with a high degree of spatial resolution and allowed pressor sites to be precisely localised in the region of ventrolateral medulla with the highest density of PNMT-LI cells.

Animals↗

The accuracy of the pulse oximeter in neonates.

The Nellcor pulse oximeter was studied in 16 newborn infants. The transcutaneous oxygen saturation (TCSaO2) was compared to both fractional saturation and functional saturation. TCSaO2 was found to be closer to fractional SaO2. 95% prediction intervals were established for the estimation of arterial oxygen saturation (SaO2) from TCSaO2. At a pulse oximeter reading of 85% to 90%, SaO2 could be as low as 83% and as high as 98%.

Humans↗

Studies on the metabolic behaviour of industrial actinide-bearing aerosols after deposition in the rat lung: an experimental basis for interpreting chest monitoring data and assessing limits on intake for workers.

UNLABELLED: The metabolism of 239Pu and 241Am in 3 site-specific industrial dusts has been studied after their deposition in the rat lung. A comparative experiment has also been carried out with a mixture of these actinides inhaled as their nitrates. The aim of this study was to provide an experimental basis for assessing limits on intake and to establish whether the 239Pu content in the lungs could be interpolated from measurements of 241Am. THE RESULTS: 1 demonstrate the wide differences in the lung retention kinetics of the actinides and in the absolute and relative amounts translocated to the blood that can occur for industrially produced materials; 2 show that the annual limits on intake (ALIs) for the different materials vary between those postulated for class W and Y compounds by the International Commission on Radiological Protection; 3 indicate that acute intakes of 239Pu equivalent to the ALI can, depending on the nature of the dust, be estimated from 241Am chest monitoring data at times from a few days up to about 3 years after exposure.

Aerosols↗

Metabolism of uranium in the rat after inhalation of two industrial forms of ore concentrate: the implications for occupational exposure.

Aerosols produced from two commercially available ore concentrates in which the uranium was present essentially in the one as ammonium diuranate (ADU) and in the other as uranium octoxide (U3O8) were administered to rats. The results show that: 1 uranium in the ADU bearing material was cleared rapidly from the lungs, mainly to the blood, such that the retention kinetics were similar to those for a class D (highly transportable) compound as defined by ICRP; 2 uranium in the U3O8 bearing material was removed from the lungs principally by mechanical processes, the retention kinetics in this case being similar to those defined for a class Y (poorly transportable) compound; 3 for both materials the distribution of uranium amongst body tissues and the fraction of the systemic content excreted in urine were similar to those obtained after the injection of soluble hexavalent compounds; 4 for workers potentially exposed to both these materials, urine monitoring and lung radioactivity counting measurements should be used in addition to air sampling procedures for assessing the intake of uranium. 5 intakes of the ADU bearing material should be restricted to those permitted for short-term exposures on the basis of chemical toxicity, whereas those for the U3O8 bearing material should be governed by radiation dose.

Aerosols↗

Does substance P coexist with adrenaline in neurones of the rostral ventrolateral medulla in the rat?

Spinally projecting substance P- (SP) and adrenaline-containing neurones of the rostral ventrolateral medulla are believed to be important in the tonic and reflex control of blood pressure. In this paper we used dual immunofluorescence staining to investigate the degree of co-localisation of these two putative neurotransmitters in this region. In contrast to a recent report that SP and phenylethanolamine-N-methyltransferase (PNMT) are extensively co-localised, we report here that only a small number of neurones were found to be immunoreactive for both SP and PNMT.

Animals↗