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Comparative effects of repeated parenteral administration of several chelators on the distribution and excretion of cobalt.

Effects of repeated ip administration of glutathione, N-acetyl-L-cysteine (NAC), 2,3-dimercaptosuccinic acid (DMSA), ethylendiamine-tetraacetic acid (EDTA), and diethylentriamepentaacetic acid (DTPA) on the distribution and excretion of cobalt were assessed in Sprague-Dawley rats. Groups of ten animals received intraperitoneally 0.06 mmol CoCl2/kg/day, three days/week for four weeks. 24 hr after the last injection, daily chelation therapy was initiated. Rats received one of the chelators or saline for 5 days. The animals were housed in metabolic cages and urine and feces were collected daily for 5 days after which time the rats were killed and the concentration of cobalt was determined in various tissues. Glutathione, NAC and DTPA significantly increased the excretion of cobalt into urine whereas EDTA, NAC and DMSA were the most effective chelators increasing the fecal elimination of cobalt. The concentration of cobalt in the various tissues was only decreased by NAC (liver and spleen) and glutathione (spleen). The observed increase in the cobalt excretion with certain chelators would suggest that increasing the duration of chelation therapy may decrease the concentrations of cobalt in tissues and hence, reduce the toxicity of the metal.

Acetylcysteine↗

Evaluation of cyclosporine nephrotoxicity in rats with various renal radioactive agents.

The efficacy of different radiodiagnostic agents for demonstrating the decline in renal function from cyclosporine (CyA) nephrotoxicity was assessed in rats receiving a standard dose of the drug for 2 wk, compared with control rats. The agents included [99mTc]DTPA, [131I]hippuran, [111In]lysozyme, [99mTc]glucoheptonate (GHA), [99mTc]dimercaptosuccinate (DMS) and [111In]aminated dextran (amdex). A small dose of [99mTc]- or [111In]DTPA was administered simultaneously to normalize the results for variations in drug response from one animal to another. There were statistically significant differences in the detectability of the renal functional impairment by plasma clearance, early and 2-hr renal uptake among the different agents. However, none was clearly superior to DTPA. This conclusion is consistent with previous studies which showed a parallel decline in glomerular filtration rate (GFR) and effective renal plasma flow in acute CyA toxicity probably due primarily to vasoconstriction.

Animals↗

Diuresis renography in patients with reduced renal function.

Diuresis renography was performed twice at an interval of one week in 13 uraemic patients without hydronephrosis. In five of the patients, the 51Cr-EDTA clearance was below 10 ml/min x 1.73 m2 for the individual kidney, in eight of the patients between 10 and 25. During the renographies, respectively, 0.5 and 7.5 mg/kg of frusemide was given I.V. at 20 min. Compared with the data from eight normal control patients, the effect of frusemide on the renography curve was very poor and varied much in both groups. Our results suggest that diuresis renography gives no conclusive information about the upper urinary tract in kidneys with a 51Cr-EDTA clearance below 25 ml/min x 1.73 m2, even when the dose of frusemide is increased to 7.5 mg/kg.

Diuresis↗

[Ureteropelvic junction syndrome. Apropos of 59 cases diagnosed with fetal echography].

We reviewed 59 cases of ureteropelvic junction obstruction diagnosed in 55 fetuses by echographic examination during prenatal period between 1981 and 1987. Postnatal excretory urograms and voiding cysto urethrography were obtained in all patients. Quantitative renal scans with 99 m technetium labeled dimercaptosuccinic acid or 99 m technetium labeled diethylenetriamine penta acetic acid were used in 49 patients and demonstrated a renal impairment in 19 cases (38%). 8 neonates were not operated, 1 required unilateral nephrectomy and 50 were treated by the Anderson-Hynes surgical procedure. 46 (92%) among those 50 obtained a significant improvement of pelvi-caliceal dilatation or excretion; 4 (8%) only a stabilisation. Early recognition of congenital hydronephrosis is now very common. After birth renal scans provided better estimation of renal function than excretory urograms but for the graduation of the obstruction the data did not appear to be always reliable (10% of false negatives in this study). The real problem is to know within which period of time the neonates whose renal function is impaired need surgery. In our study that question cannot be given a definitive answer because of too few post operative renal scans. However, we think, just as literature data tend to prove, that those neonates required early surgery if normal renal function is to be obtained.

Female↗

Mobilization of cadmium in mice by combined treatment with N-benzyl-N-dithiocarboxy-D-glucamine and diesters of meso-2, 3-dimercaptosuccinic acid.

Mice which had received a non-lethal injection of cadmium (Cd) as CdCl2 nine days prior to therapy were treated with N-benzyl-N-dithiocarboxy-D-glucamine (BDCG) alone or in combination with either di(iso-butyl)dimercaptosuccinate (DiBDMS) or di(iso-amyl)-dimercaptosuccinate (DiADMS). Seven injections of BDCG (1.0 mmole/kg), DiBDMS (0.4 mmole/kg), and DiADMS (0.4 mmol/kg) reduced whole body Cd burdens 50%, 54% and 37%, respectively; coadministration of BDCG + DiBDMS and BDCG + DiADMS produced respective reductions of 65% and 61%. Seven injections of BDCG lowered renal Cd concentrations an average of 82%, but reduced hepatic Cd concentrations only 53%. The DMSA diesters were more effective in lowering hepatic Cd than in reducing the levels of Cd in the kidneys. The respective hepatic and renal Cd reductions were 50% and 20% after treatment with DiADMS, and were 73% and 30% after treatment with DiBDMS. Coadministration of BDCG with DiADMS reduced hepatic and renal Cd concentrations 74% and 82%, respectively, while BDCG co-administered with DiBDMS yielded respective reductions of 80% and 82%. It is suggested that combined use of these newer Cd complexing agents in studies of experimental Cd poisoning may now permit resolution of the issue of reversibility of Cd-induced nephrotoxicity.

Animals↗

Sipple's syndrome with liver tumors examined by iodine-131 MIBG and technetium-99m(V)-DMSA.

This case report describes the localization and categorization of tumors using 99mTc(V)-dimercaptosuccinic acid and [131I]metaiodobenzylguanidine scans in a very uncommon case of medullary thyroid carcinoma associated with pheochromocytoma (Sipple's syndrome) and hepatocellular carcinoma. Technetium-99m(V)-dimercaptosuccinic acid showed accumulation only in medullary thyroid carcinoma, but [131I]metaiodobenzylguanidine scans were positive in both medullary thyroid carcinoma and pheochromocytoma. In advanced Sipple's syndrome, combined use of [99mTc(V)]dimercaptosuccinic acid and [131I]metaiodobenzylguanidine may be useful for the categorization of tumor mass lesions and planning appropriate therapy.

3-Iodobenzylguanidine↗

Differential renal function in unilateral renal injury: possible effects of radiopharmaceutical choice.

An abnormal filtration fraction or a significant divergence between a kidney's ability to extract Tc-99m dimercaptosuccinic acid (DMSA) and other function parameters, such as the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF), could lead to different estimates of relative or absolute renal function, depending on the radiopharmaceutical administered. To evaluate this possible divergence, we measured the relative GFR (I-125 iothalamate), ERPF (I-131 hippurate), and Tc-99m DMSA accumulation in adult male Sprague-Dawley rats with unilateral ureteral obstruction or unilateral ischemia at various times after renal injury. The relative ERPF of the obstructed kidney was significantly greater than the relative GFR at all time periods studied; significant but less dramatic differences were noted comparing DMSA with GFR in obstruction and DMSA and ERPF with GFR in ischemia. In evaluating renal disease, it is important to consider the functional parameter reflected by the administered radiopharmaceutical as well as the underlying disease state.

Animals↗

Pediatric urologic radiology. Intervention and endourology.

Over the past 10 years new imaging and interventional techniques have drastically changed the ease and scope of urologic diagnosis and treatment. It is both rewarding and exciting to approach each clinical problem with a broad armamentarium of available studies, always seeking the most efficient and direct route to diagnosis. Similarly, radiologic interventional techniques are potentially applicable to a multitude of problems and should be innovatively considered in the urologic patient including patients in the pediatric age group.

Abscess↗

Renal handling of technetium-99m DMSA in rats with proximal tubular dysfunction.

The renal handling of technetium-99m dimercaptosuccinic acid ([99mTc]DMSA) was studied in rats before and after treatment with Na-maleate (2 mmol/kg i.v.). In the control period, when measured 2 hr after the intravenous injection of [99mTc]DMSA, 39.9% of the injected dose was in the kidneys and 14.6% was in the bladder. After Na-maleate treatment, only 6.4% of the injected dose of [99mTc]DMSA was retained in the kidneys while 37.9% was found in the bladder. Subsequent studies revealed that Na-maleate produced a fall in the glomerular filtration rate, the effective renal plasma flow, and a generalized proximal tubular dysfunction. The latter was characterized by polyuria and an increased excretion of glucose, protein, albumin, calcium, and inorganic phosphate. It was concluded that proximal tubular dysfunction markedly alters the renal handling of [99mTc]DMSA. Whether this augmented urinary excretion is due to an inhibition of reabsorption or an enhanced cellular efflux of [99mTc]DMSA remains to be answered.

Animals↗

Antidotes for gold (sodium bis[thiosulfato]gold[I]) intoxication in mice.

Eight compounds were examined to determine their relative efficacy as antidotes in acute gold intoxication in mice after the intraperitoneal injection of 200 mg/kg of Na3 [Au(S2O3)2] X 2H2O. Of the compounds examined, 2,3 dimercaptosuccinic acid was the most effective antidote. It was noted that with D-penicillamine those animals which did not survive died sooner (in a matter of hours) than the corresponding control animals which had received no antidote (about 3 days). In subsequent experiments in which Na3 [Au(S2O3)2] X 2H2O was administered at the lower level of 140 mg/kg, 2,3 dimercaptosuccinic acid showed itself to be capable of reducing kidney gold levels by a factor of about 5 and liver gold levels by a factor of approximately 2.

Animals↗

Kidney scintigraphy in the diagnostics of urological renal diseases.

The authors report on their experiences in the diagnostics of urological renal diseases gained by 256 kidney scintigraphies of a total of 227 patients. The more important trends of progress made in the recent years in nuclear medicine are outlined. The sensitivity (93%) and specificity (86%) of the examination based on the surgical and histological findings are determined. The technical importance of the study made from several directions using up-to-date radiopharmaca is emphasized in obtaining the results being favourable even in international comparison. The importance of the coordination between the urologists and experts well-versed in nuclear medicine is pointed out in selecting the examination best suited for the purpose (dynamic, static examination). Based on the literature and on their own experiences, the diagnostic results of the examination in detecting and controlling renal diseases are summarized.

Adolescent↗