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Biomedical subjects

M M Jones

Publications and source records attributed to M M Jones.

At least 91 records · Page 5Linked to original sources
PubMed1992

Distribution and excretion of cadmium and nickel after simultaneous exposure and the effect of N-benzyl-D-glucamine dithiocarbamate on their biliary and urinary excretion.

A rat model for combined exposure to cadmium and nickel is presented that involves the administration of drinking water containing these elements over a period of 90 d. Coadministration of these two ions in drinking water leads to brain levels of both elements that are significantly higher than results from the administration of equal doses of the metals individually. The enhanced biliary excretion of cadmium in rats given sodium N-benzyl-D-glucamine dithiocarbamate (BGDTC) is almost twice as great in those animals given cadmium and nickel as in those animals given cadmium only. The excretion of nickel is reduced by the administration of this chelating agent. Although equal amounts of nickel and cadmium were administered to these animals, liver and kidney cadmium levels were approximately 100 times greater than the corresponding nickel levels. The results suggest that combined exposure to these elements may lead to enhanced levels of nickel and cadmium in the brain and a level of nervous system damage not predictable from information obtained under conditions of exposure to only one of these elements.

Administration, Oral↗
PubMed1992

Cadmium mobilization in vivo by intraperitoneal or oral administration of monoalkyl esters of meso-2,3-dimercaptosuccinic acid in the mouse.

The relative activities of a series of nine monoalkyl esters of meso-2,3-dimercaptosuccinic acid have been examined as agents for the mobilization of cadmium from mice one week after intraperitoneal administration of cadmium chloride. Eight of these are newly synthetized; all are of the type ROOCCH(SH)CH(SH)COOH, were R = Me, MMDMS; R = C2H5, MEDMS; R = (CH2)2CH3, Mn-PDMS; R = CHMe2, Mi-PDMS; R = (CH2)3CH3, Mn-BDMS; R = CH2CHMe2, Mi-BDMS; R = (CH2)4CH3, Mn-ADMS; R = (CH2)2CHMe2, Mi-ADMS; and R = (CH2)5CH3, Mn-HDMS. All are soluble in dilute sodium bicarbonate solutions and can be administered as aqueous solutions. Cadmium mobilization data were collected on each compound using mice previously loaded with cadmium; the monoesters were administered at a level of 0.40 mmol/kg intraperitoneally daily for five days. Data on whole body cadmium mobilization indicated that the monoester with the isoamyl group was the most effective under the conditions used. The relative whole body cadmium mobilization increased with the number of carbon atoms in the alkyl group of the monoester up to C5 and then decreased for the C6 compound. Cadmium removal from the kidneys and liver was also measured. It was found that the monoisoamyl ester was the most effective in removing cadmium from both the liver and the kidneys. The monoisoamyl ester also proved to be very effective in mobilizing cadmium from both the liver and the kidneys when given orally. This is the first compound which is reported capable of mobilizing cadmium in vivo from aged deposits after oral administration.

Animals↗
PubMed1992

Evidence of active transport of cadmium complexing dithiocarbamates into renal and hepatic cells in vivo.

A study was made of the effects of certain inhibitors of transport systems on the actions of four cadmium (Cd) complexing N,N-disubstituted dithiocarbamates (DTCs) in mobilizing murine renal and hepatic Cd in vivo. Probenecid, the prototypical antagonist of organic anion transport in the kidney, when given 1 hr prior to each DTC, sharply suppressed the DTC-induced reduction of renal Cd but was virtually without effect on mobilization of Cd from liver. Sulfinpyrazone, which blocks tubular reabsorption of uric acid and also inhibits transport of a variety of organic acids, inhibited markedly the mobilization of both renal and hepatic Cd by DTCs. Phlorizin, an inhibitor of tubular sugar reabsorption, did not affect the Cd mobilizing actions of DTCs in any consistent fashion. We propose that the high degree of selectivity of DTCs in mobilizing renal and hepatic Cd is dependent, at least in part, upon active transport of DTCs into these tissues via the organic anion transport systems. This report presents the first evidence that compounds of the (R)2NCSS- class may gain access to intracellular space by an active, carrier-mediated process.

Animals↗
PubMed1992

Short-duration spaceflight impairs human carotid baroreceptor-cardiac reflex responses.

Orthostatic intolerance is a predictable but poorly understood consequence of space travel. Because arterial baroreceptors modulate abrupt pressure transients, we tested the hypothesis that spaceflight impairs baroreflex mechanisms. We studied vagally mediated carotid baroreceptor-cardiac reflex responses (provoked by neck pressure changes) in the supine position and heart rate and blood pressure in the supine and standing positions in 16 astronauts before and after 4- to 5-day Space Shuttle missions. On landing day, resting R-R intervals and standard deviations, and the slope, range, and position of operational points on the carotid transmural pressure-sinus node response relation were all reduced relative to preflight. Stand tests on landing day revealed two separate groups (one maintained standing arterial pressure better) that were separated by preflight slopes, operational points, and supine and standing R-R intervals and by preflight-to-postflight changes in standing pressures, body weights, and operational points. Our results suggest that short-duration spaceflight leads to significant reductions in vagal control of the sinus node that may contribute to, but do not account completely for, orthostatic intolerance.

Adult↗
PubMed1992

Effectiveness of chemical agents in removing platinum from DNA isolated from cisplatin-treated HL-60 cells.

Human promyelocytic leukemia cells, HL-60, were treated with cisplatin [cis-diamminedichloroplatinum (II)] (2 mM, 1 h). DNA-cisplatin-protein complexes were isolated and exposed to thiourea (1 M), NaCN (100 mM), diethyldithio-carbamate (500 mM), or N-methyl-D-glucamine dithiocarbamate (500 mM) for 12 h. The release of platinum was measured by atomic absorption spectroscopy. Sodium cyanide was the most effective agent, releasing about 90% of the DNA-bound platinum. Thiourea was the least effective agent, while dithiocarbamates exhibited an intermediate. The ability of the same group of agents to split the proteins off from the protein-cisplatin-DNA complex was also evaluated and similarly dithiocarbamate were also the most effective.

Chelating Agents↗
PubMed1992

Association between increased atrial natriuretic peptide and reduced cisplatin nephrotoxicity in rats.

Plasma atrial natriuretic peptide (ANP) concentrations were monitored in two experimental models of protection from cisplatin nephrotoxicity. Sprague-Dawley rats made diabetic with streptozotocin (65 mg/kg) were protected from cisplatin-induced nephrotoxicity when compared to control rats as indicated by reduced plasma creatinine (0.49 +/- 0.02 vs. 0.9 +/- 0.06 mg/dl; P less than .001) and blood urea nitrogen concentrations (18.51 +/- 1.4 vs. 43.08 +/- 2.1 mg/dl; P less than .001). Plasma ANP was also increased with experimental diabetes (76.5 +/- 8.98 fmol/ml) vs. normoglycemic controls (43.8 +/- 8.9 fmol/ml; P less than .02). When diabetic rats were treated with insulin, the renal protection observed with the diabetic state was reversed (creatinine, 0.70 +/- .05 mg/dl); plasma ANP concentrations were also reduced (52.2 +/- 15.2 fmol/ml). Renal platinum concentrations were significantly lower in the diabetic group and the reversal of diabetic-induced renal protection with insulin was associated with increased renal platinum concentrations. In rats given a single i.p. dose of cisplatin (5 mg/kg), a reduction in cisplatin-induced nephrotoxicity was observed when 5% NaCl was the vehicle of choice compared to that seen in rats given the same dose of drug in 0.9% saline (creatinine, 0.43 +/- 0.07 with 5% NaCl vs. 0.63 +/- 0.03 with 0.09% NaCl). NaCl (5%) administration also resulted in increased plasma ANP concentrations when compared to rats receiving equivalent volumes of 0.9% NaCl (88.4 +/- 6.2 vs. 50.5 +/- 5.6 fmol/ml, respectively). These data suggest that increased endogenous ANP may be a mechanism of renal protection common to both experimental diabetes and hypertonic saline administration. Chronically increased ANP may prevent renal accumulation of platinum in the kidney.

Animals↗
PubMed1992

Enhanced mobilization of hepatic cadmium in mice upon coadministration of an N, N-disubstituted dithiocarbamate and an alkyl monoester of dimercaptosuccinate.

Oral (po) administration of mono-iso-amyl (2,3-dimercapto) succinate (Mi-ADMS), 0.5 mmol/kg for three consecutive days, to mice previously injected with cadmium (Cd) chloride reduced the whole body Cd burden 34%. Intraperitoneal (ip) administration of N-iso-amyl-N-glucaminedithiocarbamate (i-AmGDTC) by the same regimen reduced total body Cd 41%. Coadministration of the two compounds reduced the whole body Cd burden 60% (p less than 0.05). The liver Cd concentration was reduced 56% and 50%, respectively, by Mi-ADMS given po and i-AmGDTC given ip, each at 0.5 mmol/kg for three consecutive days. Coadministration of the two chelators reduced the liver Cd concentration 90% (p less than 0.05). The kidney Cd concentration was reduced 10% by Mi-ADMS alone, and 60% by i-AmGDTC alone, but there was only a 47% reduction when the two chelators were coadministered, probably as a result of redistribution of mobilized hepatic Cd to the kidneys. As 50-55% of the administered Cd is sequestered in the liver in this mouse model, it is concluded that coadministration of the two chemical classes of Cd complexing agents may offer a therapeutic advantage over administration of either agent alone.

Administration, Oral↗
PubMed1992

Monoisoamyl meso-2,3-dimercaptosuccinate: interaction with metallothionein-bound cadmium in vitro and evidence of active transport into renal and hepatic cells in vivo.

Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) and the unesterified 2,3-dimercaptosuccinic acid (DMSA) were evaluated for relative reactivities against metallothionein (MT)-bound cadmium (Cd) in vitro by elution of the reaction products through Sephadex G-75 gel. After 3 hr of incubation, Mi-ADMS removed about 70% of the Cd from Cd-MT, and a new peak emerged which corresponded to that obtained by elution of a 2:1 molar mixture of Mi-ADMS and Cd. Only about 15% of the Cd was removed from Cd-MT by DMSA. After 24 hr of incubation with Mi-ADMS, no evidence remained of the presence of Cd-MT; all of the Cd was recovered in a very high molecular weight fraction and in a fraction corresponding to Cd ion. In contrast, after 24 hr of incubation with DMSA, 25% of the Cd was still present as Cd-MT, while the remainder eluted in a fraction corresponding to a 2:1 molar complex of DMSA and Cd. When Mi-ADMS was administered to Cd-bearing mice which had received an inhibitor of organic anion transport, probenecid (PBC) or sulfinpyrazone (SPZ), prior to administration of the monoester, there was a marked attenuation of the Cd mobilizing actions of Mi-ADMS as reflected in whole body Cd levels. Analysis of organ Cd concentrations revealed that PBC blocked primarily the mobilization of renal Cd by Mi-ADMS, while the principal action of SPZ in antagonizing the action of Mi-ADMS was on hepatic Cd mobilization. It was concluded that Mi-ADMS has a higher affinity for Cd in Cd-MT than does DMSA, and that the access of Mi-ADMS to intracellular Cd is, at least in part, mediated by the organic anion transport system.

Animals↗
PubMed1991

A comparative study of the influence of vicinal dithiols and a dithiocarbamate on the biliary excretion of cadmium in rat.

The effect of two vicinal dithiols, 2,3-dimercaptopropan-1-ol (BAL) and N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA), and a dithiocarbamate, sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate (MeOBGDTC), on the biliary excretion of cadmium was examined in rats. Tissue cadmium levels were also determined following the measurements of biliary excretion of cadmium. At 30 min after the injection of CdCl2.2.5H2O (1 mg/kg, iv) each rat was given 400 mumol/kg ip of one of the compounds, BAL, DMPA or MeOBGDTC. While all the compounds increased the biliary excretion of cadmium, the most effective was MeOBGDTC, whose administration resulted in a 580% increase in biliary cadmium content. The effectiveness of the MeOBGDTC may be due to the presence of both nonpolar and nonionizing polar groups attached to nitrogen. MeOBGDTC was able to mobilize cadmium to the bile even after the occurrence of the synthesis of metallothionein and the incorporation of the cadmium into it. An attempt was also made to determine the chemical nature of the Cd-MeOBGDTC complex present in the bile by comparing a newly synthesized authentic sample of Cd(MeOBGDTC)2 complex with the hot dioxane extract of the freeze-dried bile samples using thin-layer chromatography and proton NMR. The results suggested that cadmium excreted in the bile in part, is complexed to MeOBGDTC and glutathione.

Animals↗
PubMed1991

Influence of age and time of administration of dithiocarbamate analogues on cadmium retention in rats.

In the present study the influence of age and time of chelation therapy on cadmium retention in 6-, 11-and 14-day-old rats and in 6-week-old rats has been investigated. Chelating agents N-benzyl-dithiocarboxy-D-glucamine (BDCG), sodium N-(metho-xybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) and N-methyl-N-dithiocarboxy-D-glucamine (MDCG) were administered intraperitoneally to three different groups at a dose of 1 mmol kg-1 body weight on two occasions following 115mCd intraperitoneal administration; immediately and after 24 h; after 24 h and 48 h; or after 48 h and 72 h. The 115mCd retention in the whole body and organs was determined 6 days after cadmium administration. Chelation therapy very effectively reduced cadmium retention in the whole body and organs, MeOBDCG being the most effective. The effects of chelating agents were significantly more pronounced in older than younger animals and in the case of early rather than late administration. The highest fraction of cadmium administered was retained in the liver, where also the strongest effect of chelation therapy was observed. Mobilized cadmium was excreted almost exclusively by the faecal route.

Aging↗
PubMed1991

Dithiocarbamate analog N-(4-methoxybenzyl)-N-dithiocarboxy-D-glucamine reduces the retention of ingested cadmium in rats.

This study was performed to evaluate the effect of oral and intraperitoneal treatment with N-(4-methoxybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) after a single oral administration of 115mCd to 6-week-old rats. Oral treatment reduced the retention of 115mCd in the whole body, gut, liver and kidney by 5, 3, 4 and 3 times respectively, and intraperitoneal treatment reduced the retention by 7, 2.5, 16 and 4.5 times, respectively. This finding is new, since it was believed that oral dithiocarbamate treatment would increase the toxicity and absorption of ingested cadmium.

Administration, Oral↗
PubMed1991

Effects of chelating agents on the cadmium burden of cells in culture.

The effects of some new chelating agents on the cadmium burden of CHO cells in culture were investigated. The chelators were sodium-N-(4-methoxybenzyl)-D-glucamine-dithiocarbamate (MeOBG-DTC), sodium-N-benzyl-D-glucaminedithiocarbamate (BG-DTC) and diisopropylmeso-2,3-dimercapto succinate (DiP-DMSA). The results were compared with the effect of the well known dimercaptopropanol (BAL). The derivates of dithiocarbamate are much less toxic than DiP-DMSA and BAL. All chelators effectively prevent Cd uptake into the cells. Mobilization of intracellular Cd, however, is more effective by the DTC-derivatives than by DiP-DMSA or BAL. Within the cell the major fraction of Cd after 48 hours incubation is found in the nuclei and cytosol and very little in the peroxisomes. The chelating agents remove the metal mostly from nuclei and cytosol. Incubation of the cells with cadmium leads to the induction of a Cd binding protein of an apparent molecular weight of 12500 Da, presumably metallothionein. MeOBG-DTC is more effective in removing the metal from this protein than BG-DTC.

Animals↗
PubMed1991

The relative nephrotoxicity of cisplatin, cis-[Pt(NH3)2(guanosine)2]2+, and the hydrolysis product of cisplatin in the rat.

An examination of the comparative nephrotoxicity in the rat of cisplatin, its hydrolysis product (mostly cis-[Pt(NH3)2Cl(H2O)]+ under the conditions applied), and cis-[Pt(NH3)2(guanosine)2]2+ revealed that these compounds differed significantly in the extent of renal damage they produced following their i.v. injection in Sprague-Dawley rats. The hydrolysis product was found to be the most toxic of the three complexes studied and produced nephrotoxicity at doses lower than those at which cisplatin was nephrotoxic. Under the conditions used, the i.v. administration of cis-[Pt(NH3)2(guanosine)2]2+ resulted in no observable signs of nephrotoxicity at levels at which an equimolar dose of cisplatin produces clear evidence of renal function impairment and morphological alterations. The nephrotoxicity of these complexes appears to be generally related to the ease with which they undergo nucleophilic substitution reactions. The lack of substantial nephrotoxicity found for cis-[Pt(NH3)2(guanosine)2]2+ suggests that the products resulting from the action of the DNA repair processes on platinated DNA do not contribute significantly to the nephrotoxicity of cisplatin. Renal platinum levels found following the administration of these compounds correlated with the degree of nephrotoxicity produced by each compound, but no general correlation of nephrotoxicity and renal platinum levels was found. The nephrotoxicity of cis-[Pt(NH3)2Cl(H2O)+ on a molar basis was estimated to be approximately 3 times as great as that of cisplatin itself.

Animals↗
PubMed1991

Post-caesarean section analgesia: a comparison of epidural butorphanol and morphine.

Epidural butorphanol 1, 2 and 4 mg were compared with morphine, 5 mg, for postoperative analgesia in 92 consenting, healthy, term parturients who had undergone Caesarean section under epidural lidocaine anaesthesia in a randomized double-blind study. Postoperative pain was assessed using a visual analogue scale and recorded with heart rate, blood pressure and respiratory rate. The demographic characteristics, and the incidences of primary and repeat Caesarean sections, were not different among the four treatment groups. At 15, 30, 45 and 60 min after treatment the median pain scores following butorphanol were similar and lower than those following morphine (P less than 0.05). Calculated median percentage pain relief values for butorphanol were higher than morphine at each of these times (P less than 0.05). At 90 min and 2 hr the pain scores and pain relief values were similar. Beyond 45 min the number of patients requesting supplemental medication and dropping out of the study increased progressively in both the butorphanol and morphine treated patients. The attrition profiles for butorphanol were different from morphine (P less than 0.01). The median time in the study was greater than 24 hr for morphine, and 3, 2.5 and 4 hr for butorphanol, 1, 2 or 4 mg, respectively. No patient developed a clinically important change in heart rate or blood pressure, and none experienced a decrease in respiratory rate below 12 breaths.min-1. One of 69 patients (1.4 per cent) who received butorphanol developed pruritus compared with ten (43 per cent) of 23 patients who received morphine. The global assessments of the adequacy of analgesia were indistinguishable between morphine and butorphanol. Epidural butorphanol provides safe, effective postoperative analgesia, has a prompt onset, and a limited duration.

Adult↗
PubMed1991

Sodium bis(hydroxyethyl)dithiocarbamate reduces acute lung tissue damage induced by cadmium in rats.

The protective effect of three dithiocarbamates against lung tissue damage induced by a single intratracheal instillation of cadmium chloride was examined in rats. The relative efficacy of these compounds was tested by comparing characteristic features of lung tissue damage: the increase of lung weight, and the changes in the synthesis and content of structural proteins. Of three compounds administered intraperitoneally at a dose of 2.46 mmol/kg body weight, the most effective in suppressing lung damage was sodium bis(hydroxyethyl)dithiocarbamate (DEDTC). Its efficacy was dependent on the time interval between administration of cadmium chloride and the DEDTC. The parameters of lung tissue damage which were examined approached control values when DEDTC and cadmium chloride were administered simultaneously.

Animals↗
PubMed1991

Relative effectiveness of some compounds for the control of cisplatin-induced nephrotoxicity.

Several procedures which have been reported as effective for the control of cisplatin induced nephrotoxicity were compared in the Sprague-Dawley rat using the same dose of cisplatin. The treatments examined were based on the use of sodium thiosulfate, sodium diethyldithiocarbamate (DDTC), glutathione (GSH), sodium N-methyl-D-glucamine dithiocarbamate (NaG) and S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721). The differences in the effectiveness of the procedures were assessed using BUN and serum creatinine values, histopathological examination, body weight changes, and renal platinum levels as indices. The effect of such treatments on the antineoplastic activity of cisplatin were examined with both the Walker 256 carcinosarcoma in the rat and the L1210 murine leukemia in mice. Under the conditions used, GSH was found to be more effective than the other nucleophiles in protecting against the nephrotoxicity of cisplatin while providing the least amount of interference with the antitumor activity as measured against the Walker 256 carcinosarcoma and the L1210 murine leukemia. Simultaneous i.v. administration of cisplatin and any of the sulfur-containing nucleophiles leads to a significant protection against the nephrotoxicity but reduced the anti-neoplastic activity of cisplatin when measured against the Walker 256 carcinosarcoma.

Animals↗
PubMed1991

The hemodynamic effects of intubation during nitroglycerin infusion in severe preeclampsia.

The effectiveness of intravenous nitroglycerin infusion in lowering maternal blood pressure and in blunting the hemodynamic responses to endotracheal intubation was evaluated in six primigravid women with severe preeclampsia. Monitoring consisted of continuous electrocardiogram monitoring, arterial cannulation, and flow-directed pulmonary arterial catheterization in each patient. All patients underwent oxytocin induction of labor and crystalloid and/or colloid expansion to produce a pulmonary capillary wedge pressure of 10 to 15 mm Hg and a colloid osmotic pressure of greater than 17 mm Hg. Intravenous nitroglycerin was administered before induction of general anesthesia. The hemodynamic effects associated with endotracheal intubation revealed a change in the heart rate from 104 +/- 10 to 133 +/- 17 beats/min, an increase in mean arterial pressure from 134 +/- 12 to 164 +/- 32 mm Hg, and an increase in systemic vascular resistance from 1262 +/- 342 to 1351 +/- 259 dynes-sec-cm-5 that was accompanied by a small change in the cardiac index from 4.5 +/- 1.2 to 4.5 +/- 0.9 L.min-1.m-2.

Acute Disease↗