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Chromium poisoning has become one of the most common heavy metal poisoning occupational diseases with high morbidity and mortality. However, most antidotes detoxify the whole body and are highly toxic. To achieve hepato-targeted chromium poisoning detoxification, a novel hepato-targeted strategy was developed using aging erythrocyte membranes (AEMs) as biomimetic material coated with a dimercaptosuccinic acid (DMSA) nanostructured lipid carrier to construct a biomimetic nano-drug delivery system. The particle size, potential, drug loading, encapsulation rate, in vitro release, and stability of the nanoparticles (NPs) were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be phagocytized by RAW264.7 macrophage cells. The efficacy of AEM-DMSA-NPs for targeted liver detoxification was evaluated by in vitro MTT analysis and an in vivo model of chromium poisoning. The results showed that the NPs could safely and efficiently achieve targeted liver chromium poisoning detoxification. All the results indicated that the biomimetic nano-drug delivery system mediated by aging erythrocyte membranes and containing DMSA nanoparticles could be used as a novel therapeutic drug delivery system potentially targeting liver detoxification.

Background: The reliable method for determination of identity and radiochemical purity (RCP) is of great importance in radiopharmaceutical development. This is especially relevant when more than one form of radiometal/ligand complex can be formed during radiolabelling, such as complexes of 99mTc or 188Re with meso-2,3-dimercaptosuccinic acid (DMSA), where depending on the pH, metal can occur either at +3 or +5 oxidation state. The aim of our study was to evaluate possibilities for optimization of chromatographic systems leading to specific and reliable analytical method for determination of the identity and RCP of DMSA complexes with 99mTc or 188Re., Material and Methods: The commercial DMSA kits (POLATOM) were used for preparation of technetium-99m (III) and (V) complexes with DMSA. 99mTc(V)-DMSA complexes were prepared by addition of NaHCO3 to the kit vial prior to 99mTc-eluate to obtain pH ~8. 188Re(V)-DMSA was prepared either directly or using intermediate 188Re(III)-EDTA complex added to DMSA. RCP was evaluated by TLC using: ITLC-SG developed in methylethylketon, SG60 coated plates developed in: n-BuOH/H2O/CH3COOH and n-PrOH/H2O/CH3COOH systems, and in H2O. Comparative biodistribution studies were performed in normal Wistar rats., Results: Using silica gel plates and n-PrOH, H2O and acetic acid in the developing solution, we observed that 99mTc/188Re(III)-DMSA and 99mTc/188Re(V)-DMSA complexes could be well separated from each other and from the impurities in the form of free pertechnetate/perrhenate. In vivo studies showed quite different biodistribution of 99mTc(III)- and 99mTc(V)-DMSA. The trivalent complex accumulated mainly in kidneys (>40%ID), while 99mTc(V)-DMSA revealed high excretion with urine and relatively high concentration in osseous tissue (ca. 2 %ID/g). Accumulation of this complex in kidneys was very low (ca. 2.5 %ID). Biodistribution pattern of 188Re(V)-DMSA prepared directly was almost identical to that of 99mTc(V)-DMSA. Biodistribution results of the 188Re preparation obtained using 188Re(III)-EDTA intermediate indicated that the preparation contained the mixture of penta- and trivalent 188Re complexes. The quite high accumulation of radioactivity in kidneys (23 %ID) gave evidence of the presence of 188Re(III)-DMSA in this preparation, what was also confirmed by the results of TLC analysis performed using silica gel plate and n-propanol/water/acetic acid as developing system., Conclusions: Based on our study, we have made recommendation on the suitable methods for investigations of RCP of DMSA complexes, i.e.: SG60 plates developed in the mixture of n-propanol/water/acetic acid, which enable determination of the tri- and pentavalent DMSA complexes, as well as, the pertechnetate/perrhenate impurity, and developed in water for determination of the colloidal residue.

The reasons for the rise in autism prevalence are a subject of heated professional debate. Featuring a critical appraisal of some research used to question whether rising levels of autism are related to environmental exposure to toxins (Soden et al. 2007, Barbaresi et al. 2009, Thompson et al. 2007) we aim to evaluate the actual state of scientific knowledge. In addition, we surveyed the empirical research on the topic of autism and heavy metal toxins. In our opinion empirical investigations are finding support for a link with heavy metal toxins. The various causes that have led to the increase in autism diagnosis are likely multi-faceted, and understanding the causes is one of the most important health topics today. We argue that scientific research does not support rejecting the link between the neurodevelopmental disorder of autism and toxic exposures.

Arsenic is a naturally occurring, highly toxic environmental pollutant. Fourier transform infrared (FT-IR) spectroscopy is a non-disturbing technique which provides quantitative information about the molecular composition of biological samples. The aim of this work is to study the compositional and structural changes at the molecular level occurring in gill tissues of Labeo rohita fingerlings due to arsenic exposure for various exposure periods by using FT-IR spectroscopic technique. The results of the present study suggest that arsenic exposure causes significant changes on the major biochemical constituents such as proteins, lipids and nucleic acids in the gill tissues of L. rohita. The changes are more pronounced as the period of exposure is increased. The significant decrease in the intensity and area of the amide I peak and CH(3) asymmetric stretching band suggests an alteration in the protein profile and lipid levels respectively, due to arsenic exposure. The amide A peak shifts suggests a change in the level of protein amide hydrogen bonding due to arsenic exposure. Further, the treatment with meso-2,3-dimercaptosuccinic acid (DMSA) improves the levels of biochemical constituents significantly, which suggest that DMSA treatment reduces the toxic effects and helps the recovery of gill tissues and its return to the level of the control.

Background: Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment., Aim: To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis., Methods: Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 +/- 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic) were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 +/- 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic) were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d) and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT) were performed for all patients., Results: Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% +/- 3.8 to 15.2% +/- 2.2, p < 0.001 in Gr I as compared to 10.6% +/- 4.6 to 13.5% +/- 3.6 in Gr 2, p < 0.001). In 8 patients (45%, 3 pts from Gr 1 and 5 pts from Gr 2) DMSA uptake remain unchanged. The mean 8 hrs UNa excretion after intravenous furosemide was above 80 meq/l and was higher in Gr 2 as compared to Gr 1 respectively (136 +/- 37 meq/l) VS 100 +/- 36.6 meq/l, P = 0.05). Finally, basal global renal DMSA uptake was decreased in 80% of patients; 22.5 +/- 7.5% (NL > 40%), as compared to normal calculated creatinine clearance (CCT 101 +/- 26), and measured CCT of 87 +/- 30 cc/min (P < 0.001)., Conclusion: A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined.

Background: The lead mobilization test reflects the mobilizable and likely toxicologically active fraction of the lead body burden. We propose a safe and convenient protocol for this test, to assess concomitant copper and zinc excretion and to determine the size of the chelatable lead pool in nonoccupationally exposed adults., Methods: The study population included 80 white adults: 40 controls [median blood lead concentration (PbB), 25 microg/L] and 40 lead-exposed individuals (315 microg/L). After collection of 4- and 24-h baseline urine specimens and a blood sample, dimercaptosuccinic acid (DMSA) was administered orally (1 g), and additional 4- and 24-h urine specimens were obtained. Determinants of the chelatable urinary lead (DMSA-PbU) were traced by linear regression analysis., Results: Urinary DMSA and lead excretion peaked within 2-3 h after DMSA administration. The amounts of DMSA, lead, copper, and zinc recovered in the 4-h urinary collections were highly correlated with those in 24-h collections (r = 0.857, 0.859, 0.958, and 0.757, respectively). At PbB concentrations >300 microg/L, the relationship between DMSA-PbU and PbB showed a steep increase and a widespread dispersion of DMSA-PbU around the regression line. After DMSA, copper and zinc excretion rates were increased up to 91- and 33-fold, respectively. No side effects were reported after DMSA., Conclusions: Determination of DMSA-PbU in a 4-h collection after DMSA is convenient, apparently safe, and inexpensive. An upper reference limit value of 22 microg/4 h is proposed for Belgian reference individuals. The diagnostic value of DMSA-PbU is likely to be contributive for PbB >300 microg/L.

Unlabelled: This study assessed pentavalent 99mTc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy., Methods: SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq 99mTc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade., Results: Approximately 95% of both benign and malignant primary brain tumors were demonstrated by 99mTc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. The delayed uptake ratio, retention ratio and retention index were higher in the malignant tumors than the benign tumors., Conclusion: Technetium-99m(V)-DMSA washout from the tumor was highly dependent upon its histology and histologic malignancy. The delayed uptake ratio considerably reflected tumor histology and differentiated benign tumors from malignant tumors. The retention ratio and retention index significantly reflected tumor histology and histologic grade of primary brain tumors and clearly distinguished between benign and malignant tumors with statistically significant difference (p < 0.05). These results could suggest the clinical utility of 99mTc(V)-DMSA in imaging primary brain tumors and differentiating their histological malignancy grade noninvasively.

Unlabelled: After intravenous administration of 99mTc-DMSA, biokinetic data were collected from studies on 24 children aged from 5 wk to 14.8 yr (15 normal and 9 with renal pathology)., Methods: Patients were imaged with a gamma camera up to 30 hr postinjection and the absolute activities in the kidneys, liver, spleen, bladder, knees and whole body were estimated using an attenuation-corrected conjugate counting technique. Renal uptake and elimination rates and urinary excretion of radioactivity were also measured., Results: In children with normal renal function, maximal kidney uptake was 42.4% +/- 5.4% and was taken up with a half-time of 1.0 +/- 0.2 hr. Renal excretion amounted to 18.0% +/- 4.4% at 24 hr and was lowest in children aged less than 1 yr. In children with abnormal renal function, apart from the expected reduction in renal uptake there was evidence of wider variations in uptake rate and increased urinary excretion. Mean uptakes in liver and spleen were approximately 5% and 2%, respectively, in all patients and uptake in knees, assumed to reside in the metaphyseal growth complexes, was 1.4%., Conclusion: In children with normal renal function, there was little evidence of age-dependent biokinetic factors other than reduced urinary excretion and lower uptake in knees in children aged less than 1 yr. The results therefore suggest that a single biokinetic model may suffice for radiation dosimetry purposes in normal children irrespective of age.

Unlabelled: Radiation dosimetry was performed on 24 children (aged 5 wk to 14.8 yr) who were undergoing routine diagnostic investigation of renal impairment with 99mTc-DMSA., Methods: Organ doses were calculated using MIRDOSE 3 with biokinetic data obtained in previously described studies, and effective doses and effective dose equivalents were estimated. Interpolation by inverse weight between pediatric anthropomorphic phantoms was compared with age-matching to discrete phantoms. Administered activities were scaled by body surface area from the adult activity of 100 MBq and the resulting radiation doses in normal children were compared with those that would have resulted from a schedule based on body weight., Results: The effective doses estimated by interpolation differed by up to 46% from those based on discrete phantoms and showed less variation. In children with normal bilateral renal function, the mean effective dose per administered activity was 0.91 +/- 0.08 mSv or 0.98 +/- 0.29 mSv by the two methods, respectively. Renal pathology reduced the effective dose, on average, by 15% of the value for normal patients., Conclusion: Over the pediatric age range, the uniformity of effective dose values was improved by scaling the administered activity according to body surface area rather than to body weight.

Unlabelled: Intrarenal handling of 99mTc-DMSA is still controversial, particularly in the existence of tubular reabsorption from the tubular fluid. Experiments were performed with micropuncture technique on the rat kidney in an attempt to elucidate this question., Methods: The concentration profile of 99mTc-DMSA along the nephron was measured in fluid from Bowman's space of surface glomeruli and from the proximal and distal tubules collected by micropuncture. Superficial loops of proximal tubules were micropunctured and microperfused with 99mTc-DMSA or [99mTc] pertechnetate for 10 or 20 min at physiological flow rates; the recovery of activity was measured in the final urine., Results: Bowman's space urine contained only 14% of the 99mTc activity of arterial plasma, indicating low filtration of 99mTc-DMSA, likely due to high plasma protein binding. Tubular fluid-to-plasma activity ratios of 0.31 in the proximal tubules and 1.31 in the distal tubules suggest that 99mTc-DMSA is neither secreted nor reabsorbed along the nephron. Ninety-eight percent of the 99mTc-DMSA activity was recovered in the final ipsilateral urine, while only 0.5% was found in the urine of the contralateral kidney., Conclusion: A low fraction of 99mTc-DMSA enters the tubule by glomerular filtration and is not reabsorbed from the tubular fluid. Thus, only peritubular extraction by the tubular cell is responsible for renal uptake of 99mTc-DMSA.

We present a patient with Fanconi syndrome who demonstrated poor renal uptake of 99mTc-DMSA and high urinary concentration of the tracer. A 99mTc-DTPA scan was normal and the creatinine clearance only minimally decreased. These findings suggest that 99mTc-DMSA may be accumulated in the kidney by glomerular filtration and subsequent tubular reabsorption, with the nonabsorbed fraction appearing in the urine. In Fanconi Syndrome the tubular reabsorption of DMSA may also be reduced, thus explaining the poor renal uptake in this patient. A 99mTc-MDP bone scan showed faint renal uptake and diffuse high uptake mainly in the spine, demonstrating that the metabolic bone disease associated with Fanconi Syndrome can be another mechanism for poor renal visualization on bone scan.

Technetium-99m(V)dimercaptosuccinic acid (DMSA) scintigraphy was performed in two patients with pathologically confirmed primary amyloidosis. Both patients had tumor-like deposits of AL-type amyloid in the abdomen. Marked uptake of the tracer by the amyloid deposits was noted. Technetium-99m-(V)DMSA scintigraphy appears to be useful in detecting the distribution of amyloid deposits and in determining the appropriate site for biopsy.

We present a patient with tubulointerstitial renal disease and poor renal 99mTc-DMSA uptake. A 99mTc-DTPA scan was normal and the creatinine clearance only minimally decreased. In this case, 99mTc-DMSA uptake did not correlate with "global renal function," but rather with the functioning tubular mass.

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.

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.

The ability to evaluate kidney function in each kidney separately by quantitative SPECT was tested in 20 patients with a single kidney and varying degrees of renal disease. Technetium-99m-dimercaptosuccinic acid (99mTc-DMSA) uptake was compared with renal function measured by creatinine clearance and serum creatinine. There was a good correlation for both serum creatinine (r = 0.89, y = 24.6 *X -1.15, error = 5.6, p less than 0.001) and creatinine clearance (r = 0.76, y = 0.6 *X 0.84, error = 8.0, p less than 0.001). The results indicate that SPECT quantitation of 99mTc-DMSA uptake can be used as an indicator of the function of each kidney individually.

Technetium-99m(V) DMSA scintigraphy was performed in two patients with pathologically confirmed amyloidosis associated with plasmacytoma. Significant uptake of the tracer was found in the deposition of amyloid. Technetium-99m(V) DMSA scintigraphy could be useful in determining the appropriate region of biopsy and in forecasting the prognosis of patient with plasmacytoma.

The finding of an enhanced excretion of [99mTc]dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of [99mTc]DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of [99mTc]DMSA in a human volunteer was 5.8%. Continuous infusion of [99mTc]DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of [99mTc]DMSA 34 +/- 4 ml/min, urinary clearance of [99mTc]DMSA 12 +/- 3 ml/min. The calculated filtered load of [99mTc]DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of [99mTc]DMSA.