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M M Jones

Publications and source records attributed to M M Jones.

At least 73 records · Page 4Linked to original sources
PubMed1994

Developmental toxicity evaluation of monoisoamyl meso-2,3-dimercaptosuccinate in mice.

Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS), a new dimercaptosuccinic acid (DMSA) analog with enhanced lipophilic properties, was evaluated for potential developmental toxicity. Intraperitoneal injections of Mi-ADMS were given to female Swiss mice (0, 47.5, 95, and 190 mg/kg) on gestational d 6-15. The maternal clinical status was monitored daily during treatment. At termination (gestational d 18), dams were evaluated for clinical status and gestational outcome. Each live fetus was weighed and examined for external, visceral, and skeletal abnormalities. Although no maternal mortality was observed, treatment with 95 and 190 mg/kg resulted in maternal toxicity, manifested as reduced body weight gain during treatment and increased relative liver weight. Embryo/fetal toxicity, consisting of a significant increase in the number of late resorptions as well as in the percentage of postimplantation loss, reduced (nonsignificant) fetal body weight, and an increase in the incidence of skeletal defects, was also observed at 190 mg/kg/d. However, no treatment-related external or soft-tissue malformations or developmental variations were found in any group. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 47.5 mg/kg/d, whereas the NOAEL for developmental toxicity was 95 mg/kg/d. These results indicate that Mi-ADMS did not produce developmental toxicity in mice in the absence of maternal toxicity.

Abnormalities, Drug-Induced↗
PubMed1994

Donor follow-up of influenza vaccine-related multiple viral enzyme immunoassay reactivity.

False-positive enzyme immunoassay (EIA) tests in blood donors receiving influenza vaccine were first reported in 1991. We conducted follow-up testing for 6 months of those donors with multiply reactive, but unconfirmed EIA (at least 2 positives in anti-HCV-1.0, anti-HIV-1, and anti-HTLV-I assays) with a history of recent flu vaccine to determine the duration of false positivity. Of 133,000 donors tested, 16 met study criteria; all 16 were reactive for anti-HCV, 10 were reactive for anti-HIV-1, and 12 were reactive for anti-HTLV-I. Fifteen donors were available for follow-up testing (using the original screening and supplemental tests): 10 (67%) reverted to negative for the 3 tests and 5 remained false positive for various markers at last sampling (3-6 months after vaccination). The mean duration of false positivity for those reverting to negative EIA test status, was 4.2 months (range 2-7 months) indicating a transient phenomenon and supporting studies which suggest a role for IgM in the mechanism.

Adolescent↗
PubMed1994

Cadmium mobilization by monoaralkyl- and monoalkyl esters of meso-2,3-dimercaptosuccinic acid and by a dithiocarbamate.

Syntheses and relative cadmium mobilizing properties are described for three new monoaralkyl esters (HOOCCH(SH)CH(SH)COOR, where R = phenylethyl ((CH2)2C6H5), MPhEDMS; R = 3-phenylpropyl ((CH2)3C6H5), MPhPDMS; and R = 2-phenoxyethyl ((CH2)2OC6H5). MPhOEDMS) of meso-2,3-dimercaptusuccinic acid. These were prepared by the reaction of the corresponding alcohol with meso-2,3-dimercaptosuccinic acid (DMSA) in aqueous HCl. When administered intraperitoneally to cadmium-loaded mice at 0.50 mmol/kg/day for four consecutive days, all induced significant reductions in the whole body cadmium levels. MPhEDMS, 60%; MPhPDMS, 66%; and MPhOEDMS, 58% in comparison with control levels. At the same dosage monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) and a dithiocarbamate, sodium N-benzyl-4-O-(beta-D-galactopyranosyl)-D-glucamine-N-carbodithioate++ + (BLDTC) induced reductions of 65% and 57%, respectively. Hepatic and renal cadmium were also depleted significantly, while brain cadmium levels were unchanged. These compounds induced a significant reduction in the cadmium levels of the spleen, and one, MPhOEDMS, produced a 10% decrease in pancreatic cadmium. The manner in which the later injections removed smaller fractions of the total body cadmium is consistent with a bodily distribution of these compounds by which they are concentrated primarily in the kidneys and the liver, with much smaller amounts reaching other organs. It is proposed that these compounds enter renal and hepatic cells through an anion transport system.

Animals↗
PubMed1994

Spaceflight alters autonomic regulation of arterial pressure in humans.

Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4-5 days) impairs one neural mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8-14 days. We found the following changes between preflight and landing day: 1) orthostatic tolerance decreased; 2) R-R interval spectral power in the 0.05 to 0.15-Hz band increased; 3) plasma norepinephrine and epinephrine levels increased; 4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and 5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevant reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.

Adult↗
PubMed1994

Monoisoamyl meso-2,3-dimercaptosuccinate as a delayed treatment for mercury removal in rats.

Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) was found to be superior to meso-2,3-dimercaptosuccinic acid (DMSA) in decreasing the body burden of 203Hg in rats under conditions of early treatment. In this experiment Mi-ADMS was used as late treatment for mercury removal. Albino rats aged 6 weeks and 7-day-old sucklings received a single intraperitoneal injection of 203Hg (as nitrate). Two weeks later they were treated with DMSA or Mi-ADMS (0.25 mmole/kg bw) on two consecutive days. The radioactivity in the carcass (whole body after removal of the gastrointestinal tract), liver, kidneys and brain was determined by solid crystal gamma scintillation counting six days after chelation therapy administration (3 weeks after 203Hg application). Both chelators reduced the body burden of mercury compared to controls. The effect of Mi-ADMS was superior to DMSA treatment in older rats for decreasing carcass and kidney retention, and in suckling rats for decreasing carcass, liver, and kidney retention. They were equally effective in decreasing brain retention in older rats and had no effect on brain retention in sucklings. The efficiency of Mi-ADMS in reducing the body burden of mercury was generally higher than the efficiency of the DMSA treatment. Therefore, Mi-ADMS deserves further attention as a late treatment for mercury removal.

Aging↗
PubMed1993

The effect of hydroxyl-containing dithiocarbamates on cisplatin-induced long-term renal dysfunction in Wistar rats.

The possibility of a slow, longer term deterioration in renal function following the administration of cisplatin has been little studied in animal models. To obtain data on this we have examined renal function and histopathology at 30 days post i.p. cisplatin (5 mg/kg) treatment in female Wistar rats with and without the administration of hydroxyl-containing dithiocarbamates as a protective measure. In contrast to the studies terminated at shorter times, the degree of protection furnished by the use of dithiocarbamates at longer times post-treatment is less impressive. Results suggest that a continuing deterioration in renal function occurs at times greater than 1 week post-treatment when such dithiocarbamates are administered at 1 and 3 h post cisplatin. This was evidenced in both several measures of renal function and in the histopathology of the S3 segment of the proximal tubule.

Animals↗
PubMed1993

In vivo spin trapping of nitric oxide in mice.

We report here an in vivo spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy to measure nitric oxide (.NO) production in the blood circulation of conscious mice. The method is based on the trapping of nitric oxide (.NO) by a metal-chelator complex consisting of N-methyl-D-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) to form a stable and water-soluble [(MGD)2-Fe(2+)-NO] complex, which gives rise to a characteristic three-line EPR spectrum of a mononitrosyl-Fe2+ complex (aN = 12.5 G and g(iso) = 2.04) at ambient temperatures. After simultaneous intravenous injection of sodium nitroprusside (an .NO donor) and the [(MGD)2-Fe2+] complex into the lateral vein of the mouse tail, the appearance of the three-line spectrum in the blood circulation of the mouse tail was monitored continuously by using an S-band EPR spectrometer, operating at 3.5 GHz. This represents the first spin trapping of .NO in living animals.

Animals↗
PubMed1993

meso-2,3-dimercaptosuccinic acid monoalkyl esters: effects on mercury levels in mice.

Seven monoesters of meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for relative activities in mobilizing and promoting excretion of mercury in mercury-laden mice. Compounds assessed were the ethyl (M-EDMS), n-propyl (Mn-PDMS), isopropyl (Mi-PDMS), n-butyl (Mn-BDMS), isobutyl (Mi-BDMS), n-amyl (Mn-ADMS), and isoamyl (Mi-ADMS) esters. 2,3-Dimercaptopropane-1-sulfonate (DMPS) and DMSA were used as positive controls. After the first oral dose of each compound at 0.5 mmol/kg, DMSA and DMPS reduced the corporal mercury burden 16% and 24%, respectively, compared to controls, while the monoesters effected reductions of 35% (M-EDMS) to 49% (Mi-ADMS). After the second treatment at the same dose, the respective reductions produced by DMSA and DMPS were 24% and 38%, and those conferred by the monoesters ranged from 52% (M-EDMS) to 61% (Mn-BDMS). Determination of the comparative dose-response relationships of DMSA and Mi-ADMS on corporal and renal mercury concentrations revealed the monoester to be more active than DMSA on both parameters at each dose used. The cumulative amount of mercury excreted in urine by control mice over a 3-day period was 7.08 micrograms; this was increased 22%, 85%, and 94% by daily i.p. injections of DMSA, DMPS, and Mi-ADMS, respectively, at a daily dose of 0.1 mmol/kg. The respective cumulative 3-day totals recovered in feces from control mice and from mice treated with DMSA, DMPS, and Mi-ADMS were 9.76, 8.21, 10.44, and 11.73 micrograms. Parallel daily measurements of retained whole body radioactivity from 203Hg in mice were in good agreement with the values calculated from the excretion data.

Animals↗
PubMed1993

Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice.

The therapeutic efficacy of six newly synthesized analogues of dimercaptosuccinic acid (DMSA) was investigated in acute arsenic trioxide poisoning in mice. Meso-2,3-di(acetylthio)succinic acid (DATSA) and meso-2,3- di(benzoylthio)succinic acid (DBTSA) are analogues of DMSA with protected thiol groups ("prodrugs"), and DMDMS, DEDMS, DnPDMS, and DiPDMS are various di-esters of DMSA with methyl, ethyl, n-propyl, and isopropyl alcohols, respectively. Thirty minutes after s.c. injection of an LD80 of arsenic trioxide (65 mumol/kg) male NMRI mice were treated with a single equimolar dose (0.7 mmol/kg) of DMSA i.p. or one of the analogues i.p. or via gastric tube (i.g.). Control animals received arsenic trioxide and saline 30 min later. The survival rate was recorded for 30 days. All of the animals treated with DMSA i.p. survived and all controls died within 2 days. Administered i.g., DATSA and DBTSA increased the survival rate to 29% and 43%, and injected i.p. to 86%. Treatment with DMDMS i.p. and i.g., and with DEDMS, DnPDMS, and DiPDMS i.g. did not reduce lethality. Given i.p., DnPDMS increased the survival rate to 72%, and DEDMS and DiPDMS to 86%, respectively. To investigate the efficacy of the DMSA analogues in reducing the tissue content of arsenic, male NMRI mice received an s.c. injection of an LD5 of arsenic trioxide containing a tracer dose of 73-As(III) (42.5 mumol/kg body wt). Thirty minutes later, saline (controls) or a single equimolar dose (0.7 mmol/kg) of DMSA i.p., or one of the analogues i.p. or i.g. was administered. The arsenic content of various organs (blood, liver, kidneys, heart, lungs, spleen, small intestine, large intestine, brain, testes, skeletal muscle, and skin) at 30 min, 2 h, 4 h, 6 h, and 8 h after the arsenic injection was measured using a gamma counter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Relative effectiveness of dithiol and dithiocarbamate chelating agents in reducing retention of polonium-210 in rats.

Nine different sulphur-based chelators, including dithiols and dithiocarbamates, were examined for their ability to remove Po-210 from the rat. In general, treatments merely caused a redistribution of Po-210 in the body. Greatest reduction of Po-210 in blood was achieved by 2,3-dimercaptopropanol (BAL), sodium diethyldithiocarbamate (DDTC), and N-(2,3-dimercaptopropyl) phthalamidic acid (DMPA). Nearly all the compounds tested decreased Po-210 in the spleen and muscle. On the other hand, BAL and DDTC substantially increased the accumulation of Po-210 in the brain while DMPA, DMPS (sodium 2,3-dimercaptopropane-1-sulphonate) and DMSA (meso-2,3-dimercaptosuccinic acid) increased by several times the Po-210 in kidneys. A less pronounced increase of Po-210 was sometimes observed in liver (due to DDTC and DMPA) and in muscle (due to BAL and DDTC). Three of the dithiocarbamates (BGDTC, MeOBGDTC and BLDTC) did not increase accumulation of Po-210 in the brain and muscle but they reduced Po-210 in blood to a lesser degree than DDTC. A derivative of DMSA (Mi-ADMS) reduced Po-210 in blood, bone and muscle more than DMSA, but at the same time increased Po-210 in the kidney. When BAL or DDTC were combined with other agents there was a greater reduction in the whole-body burden of Po-210. Removal of Po-210 from the bone, spleen and kidneys by BAL was increased by repeated treatment. However, under similar experimental conditions the effect of a single injection of BAL on Po-210 in blood was less pronounced when the period of observation was prolonged. Total-body retention of Po-210 could not be reduced to less than 85% of the untreated controls by any of the chelators tested. In spite of this some of them (BAL, DMPS, DMSA, DMPA) could still have a useful role in reducing the toxicity of Po-210.

Animals↗
PubMed1993

Superiority of Mi-ADMS to DMSA as parenteral treatment for decreasing mercury (203Hg) body burden in rats.

The efficiency of meso-2,3-dimercaptosuccinic acid (DMSA) and the monoisoamyl ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) in decreasing 203Hg retention was evaluated in rats in relation to age and time of treatment. The experiments were performed on six-week- and seven-day-old Wistar rats, which received 203Hg by intraperitoneal administration. The chelators DMSA or Mi-ADMS were also administered intraperitoneally, twice, on two consecutive days, in doses of 0.25 mmol/kg body weight as early (0.5 and 24 h) or delayed treatment (24 and 48 h, or 48 and 72 h) after 203Hg administration. The retention of 203Hg was determined in the carcass, liver, kidneys and brain six days after administration using gamma scintillation counters (double crystal, well type). In all experimental conditions, regardless of the animals' age and time of chelation therapy, Mi-ADMS was found to be superior to DMSA in reducing the body burden of 203Hg in whole body and organs. Mi-ADMS therefore seems to be a very promising chelator in the treatment of mercury poisoning.

Animals↗
PubMed1992

Mobilization of lead in mice by administration of monoalkyl esters of meso-2,3-dimercaptosuccinic acid.

The following six monoalkyl esters of meso-2,3-dimercaptosuccinic acid (DMSA) were synthesized and evaluated for relative activities in mobilizing lead from kidneys and brains of lead-bearing mice: n-propyl (Mn-PDMS), i-propyl (Mi-PDMS), n-butyl (Mn-BDMS), i-butyl (Mi-BDMS), n-amyl (Mn-ADMS) and i-amyl meso-2,3-dimercaptosuccinate (Mi-ADMS). DMSA was used as a positive control. When each was administered intraperitoneally (i.p.) as a single dose of 2.0 mmol/kg, DMSA lowered the kidney lead concentration 52%, while the monoesters effected reductions of 54-75%. Mn-ADMS was toxic at this dose. DMSA lowered the brain lead level 20% when given as a single dose, while the monoesters conferred reductions of 64-87%. When given as 5 daily i.p. injections at 0.5 mmol/kg, DMSA reduced the kidney lead concentration 45%, while the monoesters caused reductions of 56-73%. DMSA lowered the brain lead concentration 35% on the 5-day treatment regimen, while the monoesters evoked reductions of 59-75%. Mi-ADMS was equally effective when given orally or i.p. The i.p. LD50 value of this analog in mice is 3.0 mmol/kg, a value which lies between the reported LD50 doses of DMSA (16.0 mmol/kg) and dimercaprol (1.1 mmol/kg). It is suggested that the ability of these monoesters to cross cell membranes may account for their superiority to DMSA in mobilizing brain lead in this animal model.

Animals↗
PubMed1992

N-benzyl-N-lactyl dithiocarbamate treatment of mice after chronic cadmium administration.

Administration of N-benzyl-N-lactyl dithiocarbamate (BLDTC) to mice after chronic cadmium (Cd) administration evoked a prompt, dose-dependent reduction of the whole body burden; 75% of the retained Cd was mobilized and excreted after 20 i.p. injections of BLDTC at 1.0 mmol/kg/injection. This same dose regimen produced 71% and 98% reductions of the renal and hepatic Cd concentrations, respectively. There was no reduction by BLDTC of the endogenous level of any of seven other metals measured: iron, magnesium, selenium, copper, calcium, zinc, and manganese. Renal proximal tubular damage in mice which received Cd followed by BLDTC was much less than that observed in kidneys from mice which received Cd alone. Chronic Cd administration led to substantial epithelial vacuolar damage to renal distal tubules, and this process was not apparently reversed or antagonized by BLDTC treatment to the extent observed in proximal tubules.

Animals↗
PubMed1992

Control of the nephrotoxicity of cisplatin by clinically used sulfur-containing compounds.

Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cis-platin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.

Animals↗
PubMed1992

The action of chelating agents in experimental uranium intoxication in mice: variations with structure and time of administration.

The determination of the relative abilities of 11 chelating agents to enhance the urinary and fecal excretion of uranium when administered 10 min after uranyl acetate dihydrate (UAD) in mice showed that the most effective of these were Tiron, desferrioxamine, and 1,2-dimethyl-3-hydroxypyrid-4-one. An increase in the interval between UAD administration and that of the chelating agent drastically reduces the net mobilization of the uranium by the chelating agents examined. When given shortly after UAD, Tiron produced the greatest reduction in renal and bone levels of uranium. None of the chelating agents were able to affect the bone levels of uranium when administered 24 hr or more after the administration of the UAD.

Animals↗
PubMed1992

Effect of dithiocarbamates and dithiocarbamate-induced cadmium mobilization on essential trace metal metabolism in the female rat.

The effects of two dithiocarbamates (both of which induce an increase in the excretion of cadmium) on the biliary and urinary excretion of the essential trace elements zinc, copper, iron, magnesium, and calcium have been examined in the female Sprague-Dawley rat to estimate what alterations in the excretion of essential metals accompanies the use of these compounds. The dithiocarbamates studied were sodium diethyldithiocarbamate (DDTC) and sodium N-(4-methylbenzyl)-4-O-(beta-D-galactopyranosyl)-D-glucamine-N-carbod ithioate (MeBLDTC). DDTC induced a modest decrease in the biliary and urinary excretion of copper. The biliary excretion of both zinc and iron was significantly enhanced when MeBLDTC was given ip to normal rats, while those of copper, magnesium, and calcium were not significantly affected by this compound. DDTC treatment of normal female rats which had not been administered cadmium resulted in a slight decrease in the iron level of the liver. Treatment of rats with cadmium chloride resulted in a significant increase in the zinc and iron levels of the kidney, liver, and pancreas and an increase in the copper levels of the kidney and the liver. After a treatment with MeBLDTC, which reduced hepatic cadmium levels, only some of the levels of these essential metals were modified toward the levels found in untreated controls. Cadmium-loaded animals from which hepatic cadmium had been mobilized by MeBLDTC did not differ in renal or hepatic histopathology from the control (untreated) animals or from the group which had received cadmium only.

Animals↗
PubMed1992

Chelating agent reversal of cadmium effects on ionic transport in the isolated frog skin (Rana temporaria).

1. The application of 1 mM CdCl2 to the outside surface of frog skin causes a large increase in the potential difference (PD) across the skin and in the short-circuit current (SCC); the subsequent addition of selected dithiocarbamate chelating agents (which by themselves have no effect on PD or SCC) restored both electrical parameters to values close to initial levels. 2. The response observed on addition of the chelating agents indicates that the effect of CdCl2 is reversible and that the complexed ions do not possess the ability to initiate corresponding changes in the transepithelial ion transport processes in the frog skin.

Animals↗