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PubMed1997

Reliability of 99mtechnetium dimercapto-succinic acid uptake 2 hours after injection in hydronephrosis.

PURPOSE: The accumulation of radioactivity in the dilated collecting system potentially influences the calculation of differential renal function on the radionuclide test. We focused on this reservoir effect in unilateral hydronephrosis and assessed the reliability of calculating differential renal function by dimercapto-succinic acid (DMSA) uptake 2 hours after injection. MATERIALS AND METHODS: Unilateral partial ureteral obstruction was created in 8-week-old rats. Four weeks after surgery the animals were sacrificed 2 and 24 hours after the injection of tracer. The DMSA uptake rates of the renal parenchyma and collecting system were measured separately by autowell gamma counter. Differential function was calculated according to renal parenchymal and whole kidney (parenchyma and collecting system) uptake. RESULTS: There was a higher accumulation of DMSA in the dilated renal pelvis at 2 than at 24 hours. However, DMSA uptake in the collecting system was extremely small in comparison to that in the parenchyma. As a result; differential renal function calculated using parenchymal uptake was similar to that calculated using whole kidney uptake measured 2 and 24 hours after injection. CONCLUSIONS: Our data suggest that the pure reservoir effect of DMSA uptake at early measurement is much smaller than reported in previous experimental animal studies. Further clinical studies are needed to reexamine this reservoir effect in children with unilateral hydronephrosis.

Animals↗
PubMed1997

Effect of liposome-encapsulated meso-2,3-dimercaptosuccinic acid on mice exposed to lead through drinking water.

Liposomes are the potent carriers of therapeutic drugs for their targeted delivery to the intracellular sites specially when the drug is hydrophilic in nature and is unable to cross the cell membrane. Lead, a major source of environmental pollution, is accumulated in the body system of both animals and humans through reticuloendothelial system, the site where liposomes also get engulfed upon their entry into the body. In view of these considerations, meso-2,3 dimercaptosuccinic acid (DMSA), a potent chelating drug used in heavy metals intoxication, specially lead, was encapsulated in small unilamellar liposomes composed of phosphatidyl-choline and cholesterol (1:1) and used to evaluate its efficacy in lead intoxication. DMSA either in free form or encapsulated in liposomes was administered intravenously (2,62 mumoles/kg, three injections at a gap of 48 hours each, total 7.85 mumoles/kg) to mice which were pre-fed with lead in drinking water (500 micrograms/ml) for one month. It was found that only DMSA encapsulated in liposomes was significantly effective in reducing the level of lead in liver, kidneys and spleen at the dose administered. DMSA either in free form or encapsulated in liposomes also restored the inhibition in blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. The results suggest that liposome encapsulated DMSA may be preferred over free DMSA for reducing the body burden of lead.

Animals↗
PubMed1998

188Re(V)-DMSA revisited: preparation and biodistribution of a potential radiotherapeutic agent with low kidney uptake.

Methods of preparation and biodistribution in mice of tin-free 99Tcm(V)-DMSA and 188Re(V)-DMSA, a potential matching pair of radiopharmaceuticals for diagnosis and therapy of certain cancers, are described. Preparation of tin-free 188Re(V)-DMSA (I) is based on reduction with either SO2-releasing compounds like Na2S2O4 (30 mg Na2S2O4, 10 mg DMSA, 1 mg L-ascorbic acid, 37 degrees C, 60 min incubation), Na2S2O5 (as before, 70 degrees C, 15 min incubation), or HBr (0.2 ml 48% HBr, 0.2 ml 7 M HCl, 10 mg DMSA, 1 mg L-ascorbic acid, 70 degrees C, 60 min incubation). I exhibits significantly lower kidney uptake than tin-containing 188Re(V)-DMSA (II) (2-3% and 49% injected dose per gram organ, 1 h post-injection, respectively). HPLC profiles of I and II are similar. DMSA excess in tin-free 188Re(V)-DMSA is not responsible for the low kidney uptake of I. High kidney uptake of II is explained by formation of a mixed 188Re(V)-Sn-DMSA complex in vivo. Age-linked bone uptake in mice dependent on the maturation of the bone is demonstrated for both I and II.

Aging↗
PubMed1998

Effects of some thiol chelators on enzymatic activities in blood, liver and kidneys of acute arsenic (III) exposed mice.

The effects of meso 2, 3-dimercaptosuccinic acid (DMSA), sodium 2, 3-dimercaptopropane 1-sulfonate (DMPS) and S-adenosyl L-methionine (SAM) on the enzymatic activities of mice were studied. The mice were given intraperitoneal (i.p.) injections of these chelating agents (1 mmol/kg) and 3 h later the activity of delta-aminolevulinic acid dehydratase (ALAD) in the blood, and aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase (ALP) in the liver and kidney were determined. The activity of blood ALAD was significantly increased by the administration of DMSA and SAM while DMPS had only a moderate effect. The activities of other hepatic enzymes changed little when the mice were treated with these chelating agents, except for a significant reduction in hepatic ALP activity following DMPS administration. Arsenic (III) administration markedly increased the activities of ALT and ALP in the liver and kidneys. The changes in the enzymatic activities by treatment with arsenic were prevented by injection of DMSA, DMPS and SAM, DMSA being the most effective. These results indicate that DMSA, DMPS and SAM were not toxic to the liver or kidneys of mice and that treatment with DMSA is more effective than DMPS or SAM in protecting mice from acute hepatic or renal toxicity caused by arsenic.

Alanine Transaminase↗
PubMed1998

Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity.

Heavy metals are, unfortunately, present in the air, water, and food supply. Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare; however, when they do occur an effective, non-toxic treatment is essential. In addition, chronic, low-level exposure to lead in the soil and in residues of lead-based paint, to mercury in the atmosphere, in dental amalgams and in seafood, and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.

Arsenic Poisoning↗
PubMed1997

Clinical curative effects of dimercaptosuccinic acid on hepatolenticular degeneration and the impact of DMSA on biliary trace elements.

OBJECTIVE: To observe the biliary copper content of nonhepatolenticular degeneration (HLD) controls and changes in the trace elements in the bile, cerebrospinal fluid, blood and urine of hepatolenticular degeneration patients before and after dimercaptosuccinic acid (DMSA) treatment in order to further explore the etiological mechanism of HLD and prove the therapeutic effect of DMSA on HLD patients. METHODS: A consecutive series of 20 patients with HLD were given DMSA orally for 4 weeks. Adult dosage was 1.5 g/day and child dosage 1.0 g/day. Their bile, cerebrospinal fluid, blood and urine samples were obtained before and after treatment with DMSA through duodenal drainage and lumbar puncture. Biliary samples of 22 non-HLD controls were taken by drainage tube after surgical operation. Hitachi-208 atom absorption spectrophotometer was used to assay the content of copper, zinc and iron of each sample. RESULTS: DMSA could effectively improve the symptoms such as dysphasia, salivation, dysphagia and darkening of the skin; limb trembling and myotonia came second; but it showed no obvious effect on dysstasia, limb contracture and deformity, and hepatosplenomegaly. It was effective for the patients who were younger and had no obvious hepatic damage. No serious side effects were seen through the course of treatment. Laboratory study showed that biliary copper content of HLD patients was evidently lower than that of non-HLD controls (P < 0.01); DMSA could evidently improve biliary copper excretion besides clearly increase urinary copper excretion (P < 0.01) and had nothing to do with biliary zinc excretion (P > 0.05). CONCLUSIONS: Biliary copper excretion disturbance participates directly in the pathophysiology of copper retention of HLD patients. DMSA is a favorable cupruretic drug for patients with HLD.

Adolescent↗
PubMed1998

Assessment of infective urinary tract disorders.

Urinary tract infection (UTI) is common in children, particularly in the youngest age groups. There is a risk for progressive deterioration of renal function in these children if aggravating factors such as gross reflux and/or outflow obstruction of the urinary tract are present. In this review the pros and cons of available scintigraphic and radiological imaging techniques for the work-up of these children are presented. Ultrasound can be used in the acute phase to exclude obstruction but can not reliably show transient or permanent parenchymal lesions. The presence of reflux can be established with X-ray or direct nuclide cystography. The X-ray technique gives good morphological information and has a grading system with prognostic relevance. Both techniques are invasive and great care must be taken to keep the radiation burden down with the X-ray technique. Indirect nuclide cystography following a renographic study is non-invasive but has a lower sensitivity than direct techniques. More experience is needed with the indirect technique to evaluate the consequences of its apparently low sensitivity. Urography has a limited place in the acute work-up of urinary tract infection but can be used to look for renal scarring 1-2 years after an acute pyelonephritis. The 99mTc dimercaptosuccinic acid (DMSA) scan can be used during the acute UTI to show pyelonephritic lesions with good accuracy and/or during the follow-up after six months to show permanent lesions. The acute DMSA scan can be omitted. An early treatment is more important than an early scan!

Child↗
PubMed1998

[Lead intoxication and amyotrophic lateral sclerosis].

A seventy-six-year-old patient developed a bulbar form of amyotrophic lateral sclerosis, after chronic lead intoxication from drinking water. Treatment with 2,3 dimercaptosuccinic acid was administered for six months and had no effect on clinical course. We discuss the imputability of lead as a possible etiological factor.

Aged↗
PubMed1997

[Contrast analysis of brainstem auditory evoked potential in untreated and treated hepatolenticular degeneration patients with treatment of combining traditional Chinese and Western medicine].

OBJECTIVE: To observe the effect of combination therapy of traditional and Western medicine (TCM-WM) on brainstem auditory evoked potential (BAEP) in hepatolenticular degeneration patients. METHODS: BAEP was recorded and analyzed in 65 patients with hepatolenticular degeneration (HLD) before and after decoppered TCM-WM treatment. RESULTS: The peak latency (PL) and interpeak latency (IPL) of BAEP in untreated patients were greatly increased compared with those of control group, especially in the prolongations of III, V, III- V and I-V. The PL and IPL improved as improvement of clinical symptoms in HLD patients treated with TCM-WM than that in untreated patients. The abnormal rates of men and women in BAEP were decreased from 21.97% and 19.05% in untreated patients to 9.09% and 6.75% in treated patients respectively. CONCLUSION: BAEP not only has an complementary diagnosis but also judge the efficacy of treatment on the HLD disease.

Adolescent↗
PubMed1997

[Clinical study of integrated traditional and Western medicine therapy on hepatolenticular degeneration].

OBJECTIVE: To investigate the curative effect of integrated traditional and western medicine (TCM-WM) therapy on hepatolenticular degeneration (HLD). METHODS: Eighty patients with HLD were divided randomly into two groups (TCM-WM group and WM group), TCM-WM group (40 cases) were given orally dimercaptosuccinic acid (DMSA) and Gandou ([symbol: see text]) decoction for 1 month. The efficacy was compared with that of 40 cases treated with DMSA as the control. The changes of urinary trace and macro-elements before and after treatment were observed. RESULTS: The total effective rate of TCM-WM group was significantly higher than that of WM group (P < 0.05), especially more patients with hepatic type responded well to treatment with TCM-WM than with only chelating agent DMSA. Urinary trace and macro-elements were all obviously elevated in patients of two groups after treatment (P < 0.01). CONCLUSION: TCM-WM therapy appears extremely promising as new cupruretic method for treatment of HLD. It is particularly suitable for treating the patient with hepatic type.

Adolescent↗
PubMed1998

Meso-2,3-dimercaptosuccinic acid in the treatment of occupationally exposed lead workers.

The aim of this study was to evaluate the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) treatment in workers with increased lead absorption and no overt symptoms of lead poisoning. Seven occupationally lead exposed male workers with blood lead concentrations (PbB) exceeding 50 micrograms/100 ml and a positive calcium disodium ethylenediaminetetraacetate (EDTA) lead mobilization test were treated with DMSA for 19 days. Individual doses were 700 mg DMSA, three times a day from day one to five, and twice a day from day six to 19. The treatment intensified urinary lead excretion, most rapidly during the first five days. The increased elimination was followed by a decline of mean PbB to 15% of the pretreatment values. However, 15 days after the treatment, the PbB concentrations rebounded, yet kept below the baseline values and did not exceed 40 micrograms/100 ml. After repeated EDTA lead mobilization test, urine lead was 23-68% of that before DMSA treatment. It can be concluded that DMSA can effectively reduce chelatable lead in occupationally exposed workers.

Adult↗