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At least 973 records · Page 54Linked to original sources
PubMed2004

Arsenic induced inhibition of delta-aminolevulinate dehydratase activity in rat blood and its response to meso 2,3-dimercaptosuccinic acid and monoisoamyl DMSA.

OBJECTIVE: The objective of this study was to investigate arsenic induced changes in blood delta-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. METHODS: Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (III) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. RESULTS: In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (III and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (III) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (III), but at two higher concentrations (0.5 and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value. CONCLUSIONS: The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood ALAD inhibition and blood arsenic concentration than the individual treatment.

Administration, Oral↗
PubMed2004

Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: a placebo-controlled, double-blind, randomized trial.

BACKGROUND: Elevated total homocysteine (tHcy) levels may represent a potentially modifiable risk factor for cardiovascular disease in hemodialysis patients. Current therapies, including multivitamins, have been ineffective at normalizing homocysteine levels in this population; hence, new therapies are needed. There is increasing interest in the use of thiol pharmaceutical agents to displace homocysteine from albumin and improve its dialyzability. We designed a randomized, double-blind, placebo-controlled trial to determine the effect of prolonged administration of oral dimercaptosuccinic acid (DMSA) on plasma tHcy levels in vitamin-replete hemodialysis patients. METHODS: Forty-four long-term stable dialysis patients were treated for a minimum of 4 weeks with a standard multivitamin, ensuring a vitamin-replete state, then matched on the basis of tHcy levels and randomly assigned as pairs to the administration of DMSA, 2.5 mg/kg/d, or identical placebo for 8 weeks. Multivitamins were continued for the duration of the trial. RESULTS: Thirty-eight subjects (including 16 pairs) completed the trial. All important determinants of homocysteine level were balanced, and the only significant baseline difference was weight (P = 0.02). At 8 weeks, by paired analysis, there was no statistically significant difference in tHcy levels between the placebo and DMSA groups, at 21.2 micromol/L (2.87 mg/L) and 22.6 micromol/L (3.06 mg/L), respectively (mean difference, -1.4; 95% confidence interval, -5.3 to 2.5; P = 0.45). The same was true for unpaired and multivariable analyses. CONCLUSION: This randomized placebo-controlled trial found that prolonged oral administration of the thiol DMSA had no impact on tHcy levels in hemodialysis patients. Additional strategies to test the homocysteine hypothesis in this population require investigation.

Administration, Oral↗
PubMed2005

188Rhenium(V)-dimercaptosuccinic acid loaded poly(lactic-co-glycolic)acid microspheres for targeted radiotherapy: production and effectivity.

Poly(lactic-co glycolic)acid (75:25) (PLGA) microspheres for the delivery of a radiation dose to tumors were synthesized after loading the 188Re(V) labeled DMSA. The 188ReO4- in place of 99mTcO4- was replaced to label DMSA, because of their structural and chemical similarities and to make the molecule site specific for radiotherapy. The radiolabeling efficiency of DMSA was more than 97% as confirmed by ITLC. A solvent evaporation technique was used to encapsulate DMSA in PLGA microspheres. Electron microscopy demonstrated the microspheres size ranged between 0.4-1.8 microm. As demonstrated by DSC, DMSA was encapsulated (20-30%) within the microspheres in solid solution, metastable molecular dispersion or crystallization forms. In vitro release studies confirmed the stability of DMSA.

Calorimetry, Differential Scanning↗
PubMed2005

[Ingested lead cartridges cause trouble].

BACKGROUND: Lead poisoning is rare. Intake of lead shots may cause damage of the bone marrow, the nervous system, the liver, the kidneys and the endocrine organs. MATERIALS AND METHODS: We present two patients who had taken approximately 120 grams of lead shots. They developed asthenia, nausea and abdominal pain. We tried to remove the lead shots with fluids, laxatives and colonoscopy, but ultimately surgical intervention had to be performed. The patients were also treated with dimercaptosuccinic acid (DMSA). RESULTS AND INTERPRETATION: Although DMSA treatment is associated with a significant decrease in blood lead concentration and an increase of lead urinary excretion, surgical intervention is the most efficient way of treating oral intake of lead. Treatment with DMSA will probably have to go on for months in order to give an additional effect.

Adult↗
PubMed1991

Elemental mercury poisoning.

Three siblings with inhaled elemental mercury toxicity are described, and the signs and symptoms of mercury toxicity, interpretation of mercury concentrations, and management of elemental mercury exposure are reviewed. A 4-year-old girl was admitted to the hospital with a history of fever and increasing irritability, fatigue, malaise, insomnia, headache, anorexia, and ataxia. She was discharged two days later with a diagnosis of acute cerebellar ataxia. During the following 18 days, the child's condition worsened, and she was rehospitalized. Meanwhile her 11-year-old sister was hospitalized for evaluation of fatigue, weakness, lower back pain, and ataxia. The older girl's blood mercury concentration, at 5.5 micrograms/dL, was in the toxic range. Twenty-four-hour urine mercury screening confirmed mercury intoxication in both children. Questioning revealed that the girls' brother had recently spilled 0.5-1 oz of elemental mercury in the house. All family members underwent blood and urine mercury testing. The brother underwent a dimercaprol challenge to determine his tissue mercury burden, which was found to be greater than 2.4 micrograms/dL. The sisters underwent two courses of chelation therapy with dimercaprol. Symptoms persisted in all three children, and they underwent five 10-day cycles of N-acetyl-D,L-penicillamine (NAP) therapy; the youngest underwent a third dimercaprol regimen. All siblings continued NAP chelation therapy because of extensive tissue mercury burden until the results of repeated urine mercury concentration determinations were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Radionuclide evaluation of renal function.

Radionuclide renal scintigraphy offers a rapid, noninvasive method of determining individual kidney function and evaluating suspected urinary tract disorders. The initial portion of this review describes the advantages and limitations of the currently available renal radiopharmaceuticals and discusses techniques for quantitating renal functions. The latter part of the review addresses the role of radionuclide scintigraphy in the evaluation of the renal transplant, possible obstruction, reflux, renovascular hypertension, trauma, and infection.

Humans↗
PubMed1991

Pentavalent Tc-99m DMSA scintigraphy. Prospective evaluation of its role in the management of patients with medullary carcinoma of the thyroid.

Ten patients with suspected primary, recurrent or metastatic medullary carcinoma of the thyroid (MCT) were studied prospectively with Tc-99m(V) DMSA. Of these, two patients had primary disease, seven patients were asymptomatic but had persistent and serial elevations in serum calcitonin following previous thyroid resections for MCT, and one asymptomatic patient with normal serum calcitonin was studied because of suspected hilar nodes metastases. The serial calcitonin peak in the patients was 0.04-43ng/ml (normal less than 0.08ng/ml). Scintigraphy was considered positive in seven of the asymptomatic patients and equivocal in one. The two patients with primary disease had increased uptake before but not after thyroidectomy. Primary disease, localized recurrence and distant metastases in soft tissue (nine patients) and bone (one patient) were detected in these patients, and this resulted in early surgical resection (five patients) and radiotherapy (one patient). We conclude that Tc-99m(V) DMSA is a useful imaging agent in the evaluation of asymptomatic MCT patients with hypercalcitonemia.

Adult↗
PubMed1991

The pharmacokinetics and biodistribution of technetium-99m(V)dimercaptosuccinic acid in an animal tumor model.

This study used an established rabbit tumor model with squamous carcinoma to evaluate the pharmacokinetics and biodistribution of technetium-99m-(V)dimercaptosuccinic acid. A total of 54 rabbits were studied (25 with no tumor; 29 with tumor). Technetium-99m(V)dimercaptosuccinic acid had a bi-exponential blood clearance in rabbits with no tumors (28 and 325 min) and in rabbits with tumors (27 and 352 min). There was no significant difference (p greater than 0.05) in mean clearance times between the two groups and clearance appeared unaffected by tumor mass. Technetium-99m(V)dimercaptosuccinic acid had a bi-exponential cumulative urine excretion with no apparent difference in half-times between non-tumor and tumor rabbit groups (200 and 240 min, respectively). Technetium-99m(V)dimercaptosuccinic acid had a major organ biodistribution in rabbits which included bone, kidneys, bladder and the blood pool. The major route of excretion was via the urine. There was no significant difference (p greater than 0.05) in organ biodistribution between rabbits with no tumors and rabbits with tumors and there was no evidence of active uptake of technetium-99m(V)dimercaptosuccinic acid by either squamous carcinoma or inflammatory tissue.

Animals↗
PubMed1991

Abnormal cortical appearances in pediatric renal allografts.

Renal cortical studies were performed in 19 children with renal transplants. There were 10 normal studies and 9 abnormal studies, 8 of which showed multiple large focal peripheral cortical defects. The following factors showed a positive correlation: (a) the ischemia time of the transplant kidney was significantly shorter in patients with normal studies; (b) cadaver grafts were more likely to have abnormal scan appearances than living related donor grafts; and (c) in four of the five patients with double renal arteries, the scans were abnormal in multiple sites. A possible pathophysiologic mechanism to explain these scan appearances is asymptomatic segmental graft infarction secondary to progressive vascular disease. These infarcts may be a long-term sequela of ischemic insult at the time of or prior to the insertion of the renal allograft.

Child↗
PubMed1991

Pentavalent technetium-99m-DMSA uptake in a patient having multiple myeloma without amyloidosis.

A pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scan was performed on a patient with multiple myeloma without amyloidosis. A high accumulation of the tracer was found in numerous tumors. We believe that the accumulation of DMSA is unrelated to amyloidosis and that the DMSA scan may have potential for the staging of tumors in patients presenting with multiple myeloma.

Bone Neoplasms↗
PubMed1991

[Assessment of 99mTc-DMSA renography and uptake compared with creatinine clearance in rats with drug-induced nephrotoxicity--I. Gentamicin-induced nephrotoxicity].

For evaluation of technetium-99m dimercaptosuccinic acid (99mTc-DMSA) renal uptake as an absolute renal function, 99mTc-DMSA uptake was compared with endogenous creatinine clearance (Ccr) in gentamicin-induced nephrotoxicity. Gentamicin (40 mg/kg/day) was given subcutaneously to male Wistar rats for periods of 3, 6, 9 and 12 days. On the next day, the renography was performed 2 hours following intravenous injection of 99mTc-DMSA and Ccr was measured. On the 7th day, 99mTc-DMSA uptake was significantly lower in the treated rats than that in control (32.27 +/- 0.92 vs 39.84 +/- 2.24%; p less than 0.01), but Ccr did not change (0.37 +/- 0.02 vs 0.34 +/- 0.05 ml/min/100 g; NS). On the 1st, 2nd, 4th and 8th day after single subcutaneous injection of 80 mg of gentamicin, 99mTc-DMSA uptake was measured and the histological examination was done. On the 4th day, 99mTc-DMSA uptake was significantly lower than that on the 1st day (32.32 +/- 3.00 vs 38.91 +/- 1.95%; p less than 0.01) and microscopic examinations revealed that eosinophilic granular degenerations were evident in the renal cortex. The present study suggests that 99mTc-DMSA uptake reduces earlier than Ccr in gentamicin-induced nephrotoxicity and 99mTc-DMSA uptake is a reliable indicator in the evaluation of a renal function in drug-induced nephrotoxicity.

Animals↗