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Biomedical subjects

M M Jones

Publications and source records attributed to M M Jones.

At least 199 records · Page 11Linked to original sources
PubMed1984

Comparative effects of N,N-disubstituted dithiocarbamates and dimercaptosuccinate on mobilization of methylmercury in mice.

Diethyldithiocarbamate (DDTC) and five of its N,N-disubstituted analogs were compared with dimercaptosuccinate (DMSA) for effectiveness in mobilizing and promoting excretion of methylmercury (MeHg) following administration of a sublethal dose of MeHg labeled with Me203Hg. The previously reported effectiveness of DMSA was confirmed. Of the dithiocarbamates assessed, only di(carboxymethyl)-dithiocarbamate (DCDC) was active in mobilizing MeHg, and its activity on a molar dose basis was less than that of DMSA. The disparate structural requirements of dithiocarbamates as antagonists of MeHg and of cadmium were discussed.

Aged↗
PubMed1984

Antagonists for toxic heavy metals.

From a consideration of the donor preferences of toxic metals and the acceptor preferences of commonly used therapeutic chelating agents it is often possible to get a good estimate of the kinds of chelating agent which may be effective antagonists. The relative importance of extracellular vs. intracellular metal, however, introduces an important factor which can severely limit the utility of a given chelating agent with a toxic metal with which it forms very stable complexes. In general an effective antagonists of a specific toxic metal will be a chelating agent which can gain access to the metal in vivo and which forms a very stable complex, of modest toxicity with that metal ion which is rapidly excreted without damage to the kidney or liver. Such effective antagonists are not known for all metals.

Chelating Agents↗
PubMed1984

Effects of substituted dithiocarbamates on the testicular toxicity of cadmium.

Five substituted dithiocarbamates were evaluated for effectiveness in protecting mouse testes following administration of an LD100 dose of CdCl2 X 2.5 H2O (Cd). Toxicologic responses were assessed by light microscopic, electron microscopic, and computerized image analysis techniques. Diethyldithiocarbamate (DDTC) was the most effective antagonist. N-ethyl-N-hydroxyethyldithiocarbamate (EHDC), N-methyl-N-hydroxyethyldithiocarbamate (MHDC), and dimethyldithiocarbamate (DMDC) were moderately to minimally effective, while di-(hydroxyethyl)dithiocarbamate (DHDC) afforded no protection. Degenerative changes increased progressively in severity as the time interval between administration of Cd and DDTC was increased, but remained minimal when DDTC was given as late as two hours after Cd.

Animals↗
PubMed1984

Heterocyclic N-dithiocarboxylates as cadmium antagonists: 4-hydroxypiperidine- and 4-carboxamidopiperidine-N-dithiocarboxylate.

Sodium 4-hydroxypiperidine-N-dithiocarboxylate(HP-N-DTC) and sodium 4-carboxamidopiperidine-N-dithiocarboxylate (CAP-N-DTC) were synthesized by the reaction of each piperidine analog with CS2 in the presence of NaOH. Following isolation and characterization, each dithiocarboxylate (DTC) when added to an aqueous solution of CdCl2 formed a water-insoluble complex with Cd which was shown by elemental analyses to consist of DTC:Cd in a 2:1 molar ratio. HP-N-DTC was a highly effective antagonist of acute Cd toxicity in mice, while CAP-N-DTC was less effective. When seven equimolar doses of each DTC were administered to mice which had received a non-lethal dose of CdCl2 along with 1.0 microCi of 109CdCl2 50 days earlier, both effected marked reductions of renal Cd levels. CAP-N-DTC was much more effective than HP-N-DTC in reducing the whole body Cd burden, apparently due to its more rapid depletion of hepatic Cd accompanied by an enhanced rate of Cd excretion. The data illustrate that subtle structural modifications of this class of heavy metal binding agents can yield compounds with impressive differences in pharmacologic activity.

Animals↗
PubMed1984

The effect of sodium diethanolamine dithiocarbamate on distribution and excretion of Cd in rats drinking Cd-containing water.

The effect of sodium diethanolamine dithiocarbamate (DEDTC) on the distribution and excretion of cadmium was studied in three sets of rats whose drinking water contained cadmium at three different concentrations (5, 10 and 50 mg Cd.l-1) for a period of three months. DEDTC administration (500 mg.kg-1, ip) in all exposed groups significantly increased the biliary excretion of cadmium. With the exception of animals drinking water containing the lowest concentration of CD (5 mg.l-1) the urinary excretion was also increased.

Animals↗
PubMed1983

Mobilization of aged cadmium deposits by dithiocarbamates.

Mice with chronic cadmium intoxication were given low levels (0.6 mm/kg) of several dithiocarbamates (parent compounds: dihydroxyethylamine, iminodiacetic acid, methylhydroxyethylamine and sarcosine) in an attempt to reduce the cadmium present in the liver and kidney. Comparing the results with those obtained with the less polar sodium diethyldithiocarbamate (NaDDTC), only ammonium di(hydroxyethyl)dithiocarbamate (NH4DHE-DTC) possessed a similar ability to reduce kidney cadmium levels. Under the experimental conditions employed, the reduction obtained with NH4DHE-DTC was less than that effected by a comparable dose of NaDDTC. A subsequent dose-dependence study showed, however, that sodium di(hydroxyethyl)dithiocarbamate (NaDHE-DTC) is quite effective at higher dosage levels (up to 5.5 mmoles/kg) where substantial reductions in both kidney (89% mobilization) and liver (38% mobilization) stores of cadmium were observed. High doses of the NaDHE-DTC are well tolerated as the LD50 of this compound in mice is greater than 19.8 mmoles/kg.

Animals↗
PubMed1983

Ethylenediaminetetra(methylenephosphonic) acid (EDTPO) as a therapeutic chelating agent.

Ethylenediaminetetra(methylenephosphonic) acid (EDTPO), when administered as its calcium salt, is an effective antidote for acute intoxication by a number of metal ions. Significant antidotal action was found for the following cations: Cd2+, Ni2+, Zn2+, Pb2+, Be2+ and UO2+(2). Because EDTPO is capable of chelating more than one calcium ion, better results were obtained when the Ca2EDTPO complex was administered.

Animals↗
PubMed1983

Work in progress: potential oral and intravenous paramagnetic NMR contrast agents.

The potential use of paramagnetic compounds as nuclear magnetic resonance (NMR) contrast agents was examined in vitro. The T1 relaxation times for serial dilutions of Cu2+, Cr3+, Fe3+, and Mn2+ ions in saline, gadolinium oxalate (a potential oral contrast agent) in suspension, and chromium EDTA (a potential intravenous contrast agent) in solution were determined. The effect on T1 of increasing the concentration of oxygen in solution was also examined. The relative magnitude of the decrease in T1 was, as expected, proportional to both the concentration of the paramagnetic substance and its effective magnetic moment. Thus NMR has the potential to detect differences in tissue oxygenation. By incorporating paramagnetic metal ions into insoluble compounds or stable complexes, toxicity can be dramatically reduced while maintaining a significant paramagnetic effect. Highly insoluble paramagnetic compounds or stable paramagnetic ion complexes can thus be utilized as effective NMR contrast agents with significantly diminished toxicity.

Administration, Oral↗
PubMed1983

Antidotes for acute bismuth intoxication.

Nine chelating agents were tested as antidotes for acute bismuth intoxication in mice. Of these, those with sulfhydryl groups, adjacent aromatic hydroxy groups or appropriately positioned phosphonate groups proved themselves to be effective antidotes. Of the compounds currently approved for therapeutic use, D-penicillamine was the most effective.

Acute Disease↗
PubMed1983

Cardiovascular changes after weight reduction in obesity hypertension.

Intravascular volumes and systemic and regional hemodynamic variables were measured before and after weight reduction in 12 patients with obesity and essential hypertension. These findings were compared with those in nine patients who did not have any weight loss. Reduction of mean arterial pressure significantly correlated with the fall in total body weight (r = 0.46, p less than 0.05). Total circulating and cardiopulmonary blood volumes were significantly reduced (p less than 0.05 and p less than 0.01, respectively), and these changes permitted a decreased venous return and cardiac output (p less than 0.01). This fall in cardiac output was directly related to a contracted total blood volume (r = 0.49, p less than 0.05) and decreased cardiopulmonary blood volume (r = 0.52, p less than 0.05). Patients who did not lose weight showed no changes in any of these hemodynamic measurements. In addition, weight loss was associated with reduced resting circulating levels of plasma norepinephrine (p less than 0.01), suggesting that diminished adrenergic function may also be related to weight reduction and its associated fall in arterial pressure.

Blood Pressure↗
PubMed1982

Evidence of the incorporation of normally nonaggregating hemoglobins into crystalline aggregates of deoxy hemoglobin S.

Changes in the solubility of both components of binary mixtures of sickle-cell deoxyhemoglobin (Hb degrees S) and some normally nonaggregating hemoglobins were determined by direct compositional analysis of the solution phage following sedimentation of crystalline aggregates generated from them. Increases in turbidity associated with the suspension of the crystals in solution were also monitored for each mixture. Correlations between changes in species solubility and "excess' turbidity levels were observed which define two distinct forms of interaction between hemoglobin additives and Hb degrees S. The R-state quaternary structures, COHbS and metHbS in the absence of organic phosphate, are excluded from the aggregate phase and act to lower the solubility of Hb degrees S through increased excluded volume contributions to the activity of the solution phase. Increases in turbidity which parallel this solubility change reflect the increased population of highly asymmetric Hb degrees C crystals in solution. Deoxyhemoglobin A and metHbS fixed in the deoxy conformation lower the solubility of Hb degrees S in a more complex manner, which may include the establishment of a minimum solubility. The solubility of these additives also decreases, as does the turbidity due to the resultant crystals, when the proportion of additive exceeds 40% of the total. Analysis of the composition of pellets isolated from both hybrid and nonhybrid mixtures with Hb degrees A confirms its incorporation into the aggregates. Such "mixed" crystals appear to have solubility and morphological properties different from those of Hb degrees S alone. Comparison of phase composition data from mixtures prepared with varying initial concentrations of Hb degrees S suggests that the degree of HbA incorporation into HbS aggregates is a function of the amount of Hb degrees S itself available for self-aggregation and the stage of crystal development at which HbA participates.

Crystallization↗
PubMed1982

A hypothesis for the selection of chelate antidotes for toxic metals.

The problem of finding antidotes for toxic metal species for which antidotes have not been previously reported can be approached via a consideration of the metal-ion preferences of chelating agents already in clinical use. The metal ion preferences of six types of chelating agents together with information on antidotes used for other elements in the same family in the periodic table can be used to obtain a preliminary notion of which of these six structural types might furnish efficacious antidotes. The results of animal tests on a few of these chelate types can then serve as a guide in the selection of further compounds for testing. The data from the literature on antidotes for 20 toxic metal ions is summarized to assist the selection process.

Animals↗
PubMed1982

Five-year follow-up of oestrogen therapy in 94 women.

The present paper reviews a cohort of peri- and post-menopausal women who commenced hormone therapy in 1975 with follow-up observations for 5 yr. The study indicates that more than half of the patients discontinued treatment for various reasons within the 5 yr period. The drop-out rate was proportionately much greater in the bone clinic patients than in the menopause clinic patients. The reasons for this are discussed.

Aged↗
PubMed1982

Dose-dependent response of FSH, flushes and urinary calcium to oestrogen.

The reduction of gonadotrophin levels, urinary calcium and hot flushes in post-menopausal patients by ethinyl oestradiol is shown to be dose dependent, near maximum response being achieved by a dose of 15 micrograms daily. Equivalent ethinyl oestradiol doses to a number of other gonadal hormone preparations have been assessed using the derived dose-response curve of the reduction in urinary calcium.

Calcium↗
PubMed1982

Serum aluminum levels in dialysis dementia.

Serum aluminum concentrations were measured in 7 normal persons, 47 chronic hemodialysis patients and in 10 patients with the dialysis dementia syndrome. The concentrations were (mean +/- 1 SEM): 35 +/- 3.7, 109.3 +/- 10.6, and 369 +/- 51.6 micrograms/l, respectively. These results are consistent with the theory that aluminum is involved in the pathogenesis of this syndrome. In contrast to most previous reports dialysate contaminated with aluminum could not be implicated in our patients.

Aluminum↗
PubMed1982

A comparison of diethyldithiocarbamate and EDTA as antidotes for acute cadmium intoxication.

For mice which have been given the cadmium equivalent of CdCl2 X 2 1/2H2O at a level of 10 mg/kg, diethyldithiocarbamate (DDTC) administration at 500 mg/kg leads to a higher survival rate than is found with Na2CaEDTA under identical conditions. This occurs when the interval between administration of the cadmium salt and the antidote is either one or two hours. The surviving animals, however, are found to have appreciable levels of cadmium in their brain, liver and kidney when they were treated with DDTC, though their behavior appeared to be normal. The use of 50 mg/kg of DDTC after 2 hr in such cadmium poisoned mice also leads to a higher survival rate and reduced amounts of cadmium retained in the brain, liver and kidney. Unlike the other chelating agents which have been reported as useful in acute cadmium intoxication, DDTC appears to act by forming a lipid soluble complex which is largely immobilized in lipid containing tissues of the animal's body.

Acute Disease↗