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At least 469 records · Page 26Linked to original sources
PubMed1983

Congenital renal anomaly: evaluation with 99mTc-dimercaptosuccinic acid renal scintigraphy.

Technetium 99m-2,3, dimercaptosuccinic acid (99mTc-DMSA) preferentially accumulates in the renal cortex, demonstrating functioning cortical mass. We used 99mTc-DMSA renal scintigraphy in ten patients with horseshoe kidneys and five patients with unilateral fused kidneys. The results show that 99mTc-DMSA renal scintigraphy reliably establishes the diagnosis of horseshoe kidney and clearly shows the isthmus, which is very essential for proper management. The technique also aids in the definitive assessment of separate kidney function and of total radionuclide uptake is possible using 99mTc-DMSA scintigraphy.

Adolescent↗
PubMed1996

Gallium 67 scintigraphy as a predictor of renal prognosis in primary immunoglobulin A nephropathy.

From October 1987 to September 1989, 29 patients with newly diagnosed immunoglobulin A nephropathy underwent renal gallium 67 scintigraphy. The radioisotope uptake ratio between left kidney and soft tissue was measured 48 hours after bolus injection of gallium 67. In 25 patients the ratio ranged from 1.30 to 3.56 (mean, 1.95 +/- 0.47). Ratios were not obtained in four patients because strong gastrointestinal isotope excretion. Plots of reciprocal serum creatinine concentration against time and Kaplan-Meier plots of renal survival were used to assess the predictive value of the test in 20 patients for whom long-term follow-up data were available. The radioisotope uptake ratio was negatively correlated with the slope of reciprocal serum creatinine against time (r = -0.64, P < 0.01). When the 20 patients were divided into two groups according to radioisotope uptake ratio (group A, ratio > 1.95, nine patients; group B, ratio < 1.95, 11 patients), life table analysis of renal survival showed group B to have a better prognosis than group A (P < 0.05). The results indicate that increased renal gallium uptake is predictive of a poor prognosis in patients with immunoglobulin A nephropathy.

Adult↗
PubMed2001

Effects of Lewisite on cell membrane integrity and energy metabolism in human keratinocytes and SCL II cells.

Lewisite is a highly toxic arsenic compound which can cause skin damage. In the present study effects of Lewisite on cell membrane integrity and energy metabolism as well as antidotal effects of DL-2,3-dimercaptopropanesulfonate (DMPS), and meso-2,3-dimercaptosuccinic acid (m-DMSA) were investigated in a keratinocyte derived cell line (SCL II) and primary human keratinocytes (HK). Cells were incubated in Lewisite (60 microM) containing medium for 5 min. During the following 6 h lactate dehydrogenase (LDH) activity in the supernatant, intracellular ATP content, tetrazolium reduction, glucose consumption and lactate formation were measured. Glucose consumption and lactate production were decreased in both cell lines after Lewisite exposure. In SCL II cells an increase of LDH activity in the supernatant, a decrease of ATP content, and an impaired ability to reduce tetrazolium was found 3 h after Lewisite exposure. In HK cultures tetrazolium reduction was significantly decreased already after 2 h, whereas LDH increase in the supernatant and ATP content decrease occurred only at 6 h after Lewisite exposure. When DMPS or m-DMSA was added directly after Lewisite exposure to SCL II cells, glucose consumption and lactate formation were restored and LDH leakage was prevented. SCL II cells might be more prone to membrane damage whereas in keratinocytes mitochondrial impairment seems to be the predominant effect of Lewisite.

Adenosine Triphosphate↗
PubMed2003

2,3-Dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase mercury- and cadmium-induced inhibition of delta-aminolevulinate dehydratase.

Compounds derived from Dimercaprol, such as meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS), are becoming common agents for treating humans exposed to heavy metals. Heavy metals such as Pb(2+), Hg(2+) and Cd(2+) can inhibit delta-aminolevulinate dehydratase (delta-ALA-D) activity. Delta-ALA-D catalyzes the condensation of two delta-aminolevulinic acid (delta-ALA) molecules with the formation of porphobilinogen, a heme precursor. The effects of DMSA and DMPS alone or in combination with Cd(2+), Hg(2+), or Pb(2+) on hepatic delta-ALA-D were examined. DMPS and DMSA caused a dose-dependent inhibition of hepatic delta-ALA-D. In the presence of Hg(2+) or Cd(2+) the inhibitory potency of DMPS increased. Similarly, the inhibitory effects of Hg(2+) and Cd(2+) were markedly increased in the presence of DMSA. In contrast, the inhibitory effect of DMPS was not changed by inclusion of Pb(2+). As observed with DMSA, Zn(2+) did not modified the inhibitory effect of DMPS. Data of the present report support the idea that the complexes formed (metals-DMSA or DMPS) were more inhibitory than the metal (Hg(2+) and Cd(2+)) or the chelating agent alone to the hepatic delta-ALA-D activity, in vitro. The mechanism of hepatic delta-ALA-D inhibition by Hg(2+)-DMPS/DMSA and Cd(2+)-DMPS/DMSA complexes involve the essential thiol groups of the enzyme.

Animals↗
PubMed1997

Utilization of renal slices to evaluate the efficacy of chelating agents for removing mercury from the kidney.

Mercury is an environmental contaminant that preferentially accumulates in the kidney. It has been previously shown using proton-induced X-ray emission analysis that mercury (HgCl2) accumulated in precision-cut rabbit renal cortical slices. In this study, the efficacy of seven chelating agents for the removal of Hg from renal slices has been examined. Rabbits were injected with HgCl2 (10 mg/kg) and 3 h later kidneys were sliced, or renal slices were exposed in vitro to a mildly toxic concentration of HgCl2 (5 x 10(-5)M, 4 h). The slices were then treated in vitro with 10 mM concentrations of EDTA, lipoic acid (LA), penicillamine (PA), glutathione (GSH), 1,4-dithiothreitol (DTT), DMSA, or DMPS. DMPS proved to be the most effective in mobilizing Hg from in vivo or in vitro HgCl2-exposed renal tissue ( > 85% of control after 3 h incubation). Relative efficacies for the seven agents were DMPS > DMSA, PA > DTT, GSH > LA, EDTA. The use of renal slices appears to be a useful in vitro tool for assessing the efficacy of chelating agents on mobilizing accumulated Hg from renal tissue.

Animals↗
PubMed1999

Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune function and lead-induced immunotoxicity.

Meso-2,3-dimercaptosuccinic acid (DMSA) is a drug currently employed for cheltion therapy in lead poisoning; however, little is known about its potential effects on the immune system. To examine the effect of DMSA and its capacity to reverse immunotoxicity resulting from exposure to lead in utero, female Fischer 344 rats were administered lead acetate in drinking water from 2 weeks prior to mating until parturition; DMSA was given by gavage on days 6-21 of gestation. The immune function of the female offspring was tested at 13 weeks of age. The results showed that lead (250 ppm) suppressed Th1-type responses (delayed-type hypersensitivity (DTH), interferon gamma (IFN gamma) production), enhanced a Th2-type response (interleukin-4 (IL-4) production), and increased tumor necrosis factor alpha (TNF alpha) production from macrophages. DMSA treatment (60 mg/kg per day) during pregnancy significantly lowered the blood lead levels of both the embryos and the lactating dams as well as the milk lead level of lactating dams. The chelation treatment also reversed the lead-induced alterations in pup body weight, relative spleen weight, TNF alpha, and IL-4 production. But in utero exposure to DMSA alone resulted in decreased DTH response in adult offspring. This was likely due to a reduced cell recruitment, since plasma monocyte chemoattractant protein-1 (MCP-1) levels were decreased. The DMSA-exposed offspring also demonstrated increased interleukin-2 (IL-2) production. These results suggest that DMSA reverses some of the lead-induced immunotoxicity; however, this treatment itself during embryonic development produces subsequent adult immunomodulation.

Animals↗
PubMed1999

Lead inhibits meso-2,3-dimercaptosuccinic acid induced calcium transients in cultured rhesus monkey kidney cells.

Previously we have shown that meso-2,3-dimercaptosuccinic acid (DMSA, 15-500 microM) elicits concentration-dependent increases in intracellular calcium levels ([Ca2+]i) in untreated rhesus monkey kidney cells (LLC-MK2) (Pokorski et al., 1997, unpublished results). Little is known about the restorative effects of the chelating agent 2,3-dimercaptosuccinic acid on intracellular calcium homeostasis in the presence of lead. Lead interacts at numerous sites in Ca2+ homeostasis and may mimic Ca2+ to interfere with Ca2+-mediated intracellular signaling. To examine the effects of lead on [Ca2+]i and DMSA-induced calcium transients, LLC-MK2 were plated on 35 mm coverslip dishes (10(4) cells/dish) and pre-treated with non-cytotoxic concentrations of lead (0-100 microM) for 24 h. Cells were washed, loaded with the calcium-sensitive probe Fura-2/AM, rinsed again, and examined in loading buffer in the absence of any additional lead. Intracellular calcium was measured using a dual-wavelength calcium imaging system. Basal [Ca2+]i levels did not change between Pb-exposed (0-50 microM, 24 h) and non-lead exposed cells. In cells treated with > or = 10 microM lead for 24 h, the ability of DMSA to elicit a calcium response was blocked. These results provide evidence that pre-exposure to lead blocks the entry of extracellular calcium into LLC-MK2 cells when stimulated by specific calcium mobilizing agents.

Animals↗
PubMed1999

Meso-2,3-dimercaptosuccinic acid induces calcium transients in cultured rhesus monkey kidney cells.

The maintenance of intracellular Ca2+ homeostasis is critical to many cellular functions that rely on the calcium ion as a messenger. While attempting to characterize the effects of lead on intracellular calcium levels ([Ca2+]i) in LLC-MK2 Rhesus Monkey kidney cells, we observed that treatment with the metal chelating drug, meso-2,3-dimer-captosuccinic acid (DMSA) evoked transient increases in [Ca2+]i. Changes in [Ca2+]i were monitored using the Ca2+ indicator dye Fura-2 and a dual wavelength fluorescence imaging system. In the presence of 2 mM extracellular Ca2+, DMSA treatment caused a concentration-dependent (15-500 microM) transient increase in [Ca2+]i returning to baseline levels within 30-60 s. Pharmacologic concentrations of DMSA (30 microM) stimulated a three-fold increase in [Ca2+]i, which was spatiotemporally comparable to Ca2+ transients induced by other calcium agonists. Depletion of inositol trisphosphate (IP3)-sensitive [Ca2+]i stores with the smooth endoplasmic reticulum calcium-ATPase (SERCA) inhibitor thapsigargin did not prevent DMSA-elicited increases in [Ca2+]i, suggesting that Ca2+ mobilized by DMSA was either extracellular or from an non-IP3 releasable Ca2+ pool. Treatment with glutathione, cysteine, or 2-mercaptoethanol caused similar but not identical calcium transients. Adenosine-5'-trisphosphate (ATP) also elicited transient increases in [Ca2+]i similar to those of DMSA. No transient increases in [Ca2+]i were elicited by DMSA or ATP in the absence of extracellular calcium. These data indicate that DMSA and other sulfhydryl compounds trigger an influx of extracellular calcium, suggesting a previously unobserved and unanticipated interaction between DMSA and the Ca2+ messenger system.

Adenosine Triphosphate↗
PubMed2003

Effects of dietary lead and/or dimercaptosuccinic acid exposure on regional serotonin and serotonin metabolite content in rainbow trout (Oncorhynchus mykiss).

The lead (Pb) chelator, meso-2,3-dimercaptosuccinic acid (DMSA) may be effective in reversing some of the adverse effects of Pb exposure. Pb-induced behavioral deficits observed in fish are due to disruptions in the integrative functioning of the medulla, cerebellum, and optic tectum. Pb exposure increased serotonin (5-HT) content in all three brain regions without an effect on 5-hydroxy-3-indoleacetic acid (5-HIAA). Pb exposure followed by no Pb in the diet increased 5-HT and 5-HIAA content in all three brain regions. The replacement of dietary Pb with DMSA had no effect on 5-HT and increased 5-HIAA content. DMSA increased 5-HIAA content in all three brain regions and increased 5-HT content only the optic tectum. Treatment with DMSA may be more effective than removal of Pb from the diet in reversing Pb-induced alterations in 5-HT.

Animals↗
PubMed2002

Meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA effect on gallium arsenide induced pathological liver injury in rats.

The effect of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) on gallium arsenide (GaAs) induced liver damage was studied. The oral feeding rat model was used in this study. The animals were exposed to 10 mg/kg GaAs, orally, once daily, 5 days a week for 24 weeks and treated thereafter with single oral daily dose of either 0.3 mmol/kg DMSA or MiADMSA for two course of 5 days treatment. The animals were sacrificed thereafter. Lipid peroxidation was assessed by measuring liver thiobarbituric acid reactive substance (TBARS). Liver damage was assessed by number of biochemical variables and by light microscopy. The activity of superoxide dismutase (SOD) and delta-aminolevulinic acid dehydratase (ALAD) beside reduced glutathione (GSH) concentration was measured in blood. Exposure to GaAs produced a significant reduction in GSH while, increased the oxidized glutathione (GSSG) concentration. Hepatic glutathione peroxidase (GPx) and catalase activity increased significantly while level of serum transaminase increased moderately. Gallium arsenide exposure also produced marked hepatic histopathological lesions. Overall, treatment with MiADMSA proved to be better than DMSA in the mobilization of arsenic and in the turnover of some of the above mentioned GaAs sensitive biochemical alterations. Histopathological lesions also, responded more favorably to chelation treatment with MiADMSA than DMSA.

Alanine Transaminase↗
PubMed2003

Reversal of cadmium induced oxidative stress by chelating agent, antioxidant or their combination in rat.

The influence of an antioxidant agent such as N-acetyl cysteine (NAC) or mannitol on the cadmium chelating ability of monoisoamyl 2,3-dimercaptosuccinate (MiADMS) was investigated in cadmium pre-exposed rats. This ester of 2,3-dimercaptosuccinic acid (DMSA), an accepted drug for lead poisoning, being lipophilic in nature was expected to be an efficient cadmium chelator. The treatment of cadmium intoxicated animals with MiADMS reversed cadmium induced increase in blood catalase, superoxide dismutase (SOD) and malondialdehyde (MDA), liver MDA and brain SOD and MDA levels but not the decrease in blood, liver brain reduced glutathione (GSH) and increase in oxidized glutathione (GSSG) levels, consistent with the lowering of tissue cadmium burden. The administration of NAC or mannitol reversed the cadmium induced alterations in blood and liver GSH, GSSG, blood catalase, SOD, MDA, liver SOD, MDA and brain MDA levels without lowering blood and tissue cadmium contents. However, treatments with the combination of MiADMS and NAC or MiADMS and mannitol reversed these alterations as well as reduced blood and tissue cadmium concentrations. The combined treatment with MiADMS and mannitol was better than that with MiADMS and NAC, and was significantly more effective in normalizing blood, liver GSH, GSSG, brain GSSG, and their GSH/GSSG ratios than that by either of them alone. The combined treatments also improved liver and brain endogenous zinc levels, which were decreased due to cadmium toxicity. The results suggest that the administration of an antioxidant during chelation of cadmium may provide beneficial effects by reducing oxidative stress without its cadmium removing ability.

Acetylcysteine↗
PubMed1988

Gas chromatographic analysis of urinary dimercaptosuccinic acid.

The therapeutic use of disulfhydryl compounds such as 2,3-dimercaptosuccinic acid (DMSA) for the treatment of heavy metal poisoning has generated a requirement for specific and sensitive methods to determine those compounds in biological media. We have developed a gas chromatographic assay for DMSA in urine. The use of capillary column technology eliminates the requirement for a preliminary clean-up step. Samples are first reduced electrochemically to liberate DMSA present as disulfides. The reduced product is then extracted into ethyl acetate and the organic phase removed by evaporation. The residue is derivatized with N,O-bis (trimethylsilyl) acetamide for gas chromatography. The silylated DMSA derivative is then detected with a flame ionization detector. The detection limit for DMSA is 1.9 nmol per 1-microliter aliquot of derivatized extract injected on column (detector sensitivity at 1.10(-11) A/mV). The utility of the method was demonstrated by analyzing the urine of rats orally dosed with DMSA.

Administration, Oral↗
PubMed2002

[Power Doppler sonography and acute pyelonephritis in children: comparison with Tc-DMSA scintigraphy].

UNLABELLED: Acute pyelonephritis is a common infection in children. The clinical and biological diagnosis is still sometimes difficult. For most authors, Technecium 99m dimercaptosuccinic acid scintigraphy is considered as the gold standard tool for diagnosis but it is invasive and expensive. The aim of our study was to compare the sensitivity and the specificity of B-mode sonography and power doppler to DMSA-Tc scintigraphy in acute pyelonephritis. PATIENTS AND METHODS: Forty-nine children were enrolled in this study with suspicion of pyelonephritis. All infants underwent doppler sonography and scintigraphy within 48 hours after their hospitalization. Doppler sonography criteria were increased kidney size, thickness of sinus wall, vascular defect, and various echogenicity of the kidneys (focal or diffuse hyperechogenicity or focal hypoechogenicity). RESULTS: Among 28 children with a positive scintigraphy, 15 had a positive doppler sonography (sensitivity 54%) and 13 had a negative doppler sonography. Among 21 children with a negative scintigraphy, 20 had a negative doppler sonography (specificity 95%) and one had a positive doppler sonography. CONCLUSION: In clinically suspected acute pyelonephritis, doppler sonography has a high specificity. A positive doppler sonography should avoid the use of scintigraphy.

Acute Disease↗
PubMed1999

Toxicity and osmoprotective activities of analogues of glycine betaine obtained by solid phase organic synthesis towards Sinorhizobium meliloti.

Seven analogues of the bacterial osmoprotectant glycine betaine (GB, trimethylammonioacetate), in which the methyl groups of the Me3N+ moiety are replaced by various substituents, were obtained by SPOS using Wang resin. Their biological activities (osmoprotection vs toxicity), appeared closely related to their uptake efficiency and their catabolism in the betaine-demethylating model bacterium Sinorhizobium meliloti.

Betaine↗
PubMed2001

Uptake of the 188Re(V)-DMSA complex by cervical carcinoma cells in nude mice: pharmacokinetics and dosimetry.

The uptake of the rhenium-188 (188Re(V)-DMSA) complex of dimercaptosuccinic acid by cervical carcinoma cells in nude mice was evaluated. The pharmacokinetics and dosimetry calculations in normal rats were also evaluated. The images obtained in mice did not show significant accumulation in metabolic organs and the biodistribution studies showed that 3.52 +/- 0.76% of the injected activity per gram (n = 4) was taken up by the tumor. This percentage produces a cumulated activity of 35.63 +/- 8.40 MBq h and an equivalent dose per injected activity of 260 +/- 8.91 mSv/MBq. Pharmacokinetics and dosimetry of the 1887e(V)-DMSA complex indicate that this radiopharmaceutical could be evaluated in patients with soft tissue tumors, since the risk of radiation damage to the kidney or red bone marrow could not be an obstacle for its application in therapeutic nuclear medicine.

Animals↗
PubMed1999

Preparation of [186Re]Re-DMSA and its bio-distribution studies.

99mTc(V)-DMSA is widely used for imaging medullary carcinoma and hence 186/188Re(V)-DMSA is suggested as a potential agent for treating medullary carcinoma. In the present paper, we report the work carried out for the preparation of [186Re]Re(V)-DMSA and it's bio-distribution studies in Wistar rats. The complex was prepared by reducing 186Re (100 micrograms, 0.54 microM, approximately 150 MBq) in the presence of DMSA (2 mg, 11 microM) with stannous chloride (0.4 mg, 2.2 microM) in acidic medium at pH 2. The reaction was taken to completion by heating the complex in a boiling water bath for 30 min. Bio-distribution studies carried out revealed that pharmacological behaviour of 186Re(V)-DMSA is similar to that of 99mTc(V)-DMSA except that the kidney uptake is marginally higher. The kidney uptake reduced significantly when the pH of the complex was adjusted to 8 prior to injection. The in vitro stability studies of this complex suggest that the product formed is stable and could be used for clinical trials.

Animals↗