Search

Alexithymia is a key transdiagnostic risk factor for emotion-based psychopathologies. Conceptual models specify that this is because alexithymia impairs emotion regulation. However, the extent of these putative emotion regulation impairments remains underexplored. Our aim in this study was to begin to address this gap by examining whether people with high, average, or low levels of alexithymia differ in the types of emotion regulation strategies they typically use. General community adults from the United States (N = 501) completed a battery of alexithymia and emotion regulation measures. Participants were grouped into high, average, and low alexithymia quantiles. After controlling for demographics and current levels of distress, the high, average, and low alexithymia groups differed in their use of cognitive and behavioral emotion regulation strategies. Compared to the other groups, the high alexithymia group reported lesser use of generally adaptive regulation strategies (cognitive reappraisal, approaching problems, and seeking social support) and greater use of generally maladaptive regulation strategies (expressive suppression, behavioral withdrawal, ignoring). Our data were cross-sectional and from self-report questionnaires. Future work in other cultural groups would be beneficial. Our results support the view that alexithymia is associated with impaired emotion regulation. In particular, people with high alexithymia seem to exhibit a less adaptive profile of emotion regulation strategies. Direct targeting of these emotion regulation patterns in psychotherapy may therefore be a useful pathway for the treatment of emotional disorder symptoms in people with high alexithymia. • The process model predicts that alexithymia should impair emotion regulation • We examined the emotion regulation strategy use profiles characterizing alexithymia • Alexithymia was characterized by a less adaptive emotion regulation profile: • Less use of cognitive reappraisal, approaching problems, and seeking social support. • More use of expressive suppression, behavioural withdrawal, and ignoring. [ABSTRACT FROM AUTHOR]

Background: Ever since alexithymia was defined in the 1970s, robust associations have been observed between alexithymia and a variety of symptoms of psychopathology. Alexithymia is now widely regarded as an important transdiagnostic risk factor, and it is frequently assessed in clinical and research settings. However, despite this strong interest, it remains unclear exactly why (i.e., by which mechanisms) alexithymia is linked to psychopathology. In this paper, we hypothesise that alexithymia is linked to affective disorder symptoms because alexithymia impairs people's ability to regulate their emotions, and we empirically test this hypothesis.Method: We administered a battery of psychometric measures to 501 adults in the United States, and examined the direct and indirect effects between alexithymia (Perth Alexithymia Questionnaire), emotion regulation ability (Perth Emotion Regulation Competency Inventory), and affective disorder symptoms (Depression Anxiety Stress Scales-21).Results: In the Pearson bivariate correlation matrix, alexithymia, emotion regulation difficulties, and affective disorder symptoms were all significantly correlated. In the modelling of direct and indirect effects, alexithymia was indirectly associated with affective disorder symptoms through emotion regulation difficulties (no significant direct effect).Limitations: Our online survey data were all self-report data and cross-sectional. Future longitudinal work would be beneficial.Conclusions: Our findings support contemporary theorising that alexithymia is linked to affective disorder symptoms via emotion regulation difficulties. These results help to clarify the mechanisms by which alexithymia may predispose people to affective disorder symptoms, and highlight the importance of considering the roles of alexithymia and emotion regulation in case conceptualisations and treatment planning. [ABSTRACT FROM AUTHOR]

Marfan syndrome (MFS) is a genetic disorder that affects multiple organs. Mortality imposed by aortic aneurysm and dissections represent the most serious clinical manifestation of MFS. Progressive pathological aortic root enlargement as the result of degeneration of microfibril architecture and consequential loss of extracellular matrix integrity due to fibrillin-1 (FBN1) mutations are commonly diagnosed clinical manifestations of MFS. However, overlapping clinical manifestations with other aneurysmal disorders present a significant challenge in early and accurate diagnosis of MFS. While FBN1 mutations, abnormal transforming growth factor-β signaling and dysregulated matrix metalloproteinases have been implicated in MFS, clinically accepted risk-stratifying biomarkers have yet to be reliably identified. In this review, we summarize current consensus and recent insights in the understanding of MFS pathogenesis. Finally, we introduce the application of induced pluripotent stem cells (iPSCs) as cellular models for MFS and its potential as a novel platform into providing better appreciation of mechanisms underlying MFS diverse manifestations in the cardiovascular system. [ABSTRACT FROM AUTHOR]

Cardiomyocytes (CMs) derived from human pluripotent stem cells (hPSCs) offer immense value in studying cardiovascular regenerative medicine. However, intrinsic biases and differential responsiveness of hPSCs towards cardiac differentiation pose significant technical and logistic hurdles that hamper human cardiomyocyte studies. Tandem modulation of canonical and non-canonical Wnt signaling pathways may play a crucial role in cardiac development that can efficiently generate cardiomyocytes from pluripotent stem cells. Our Wnt signaling expression profiles revealed that phasic modulation of canonical/non-canonical axis enabled orderly recapitulation of cardiac developmental ontogeny. Moreover, evaluation of 8 hPSC lines showed marked commitment towards cardiac-mesoderm during the early phase of differentiation, with elevated levels of canonical Wnts (Wnt3 and 3a) and Mesp1. Whereas continued activation of canonical Wnts was counterproductive, its discrete inhibition during the later phase of cardiac differentiation was accompanied by significant up-regulation of non-canonical Wnt expression (Wnt5a and 11) and enhanced Nkx2.5 + (up to 98%) populations. These Nkx2.5 + populations transited to contracting cardiac troponin T-positive CMs with up to 80% efficiency. Our results suggest that timely modulation of Wnt pathways would transcend intrinsic differentiation biases of hPSCs to consistently generate functional CMs that could facilitate their scalable production for meaningful clinical translation towards personalized regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract: For modeling the rate of deposition of cohesive flocs in estuaries the Krone equation is extensively used. It was derived from flume experiments on muddy sediment from the San Francisco Bay, and is applicable to low suspended sediment concentration environments in which shear-induced aggregation – the growth and break up of flocs – has a limited role. It is shown that the use of this equation can lead to erroneous estimates of the mass deposition flux at typically higher estuarine concentrations. Krone's own experimental data permit the development of a more general equation accounting for the effects of concentration and turbulent shear rate on aggregation. These effects are dramatically observed in a deposition test in which a wire mesh was inserted in the flow to change the turbulent shearing rate and increase deposition. Even with the inclusion of aggregation effect in the general equation, field-based observations from San Francisco Bay suggest that typical flumes generally may not meet the space and time scaling requirements for field application of laboratory data. Thus, although the Krone equation should be eschewed in favor of the general equation, interpretations of model-predicted deposition rate must not be accepted without robust field-based verification. [Copyright &y& Elsevier]

Despite optimal medical therapy, cardiovascular disease remains a leading cause of morbidity and mortality worldwide. One emerging therapeutic approach for treatment of cardiomyopathies is stem cell therapy. Use of stem cells for regenerative medicine has quickly evolved over the last decade. On the basis of encouraging pre-clinical results, stem cell therapy has developed rapidly into a potentially promising treatment for ischemic heart disease, myocardial infarction and congestive heart failure. In this review, we summarize the current state-of-the-art of stem cell therapy and compare collective experiences gleaned from trials using intravenous, intra-coronary and intra-myocardial delivery in exacting credible benefits. We discuss implications of clinical outcomes reported in relation to the delivered stem cells as probable destiny therapy for cardiovascular repair. [ABSTRACT FROM AUTHOR]

Abstract: Arsenic contaminated drinking water has affected more than 200 million people globally. Chronic arsenicism has also been associated with numerous neurological diseases. One of the prime mechanisms postulated for arsenic toxicity is reactive oxygen species (ROS) mediated oxidative stress. In this study, we explored the kinetic relationship of ROS with calcium and attempted to dissect the calcium ion channels responsible for calcium imbalance after arsenic exposure. We also explored if mono- or combinational chelation therapy prevents arsenic-induced (25ppm in drinking water for 4 months) neuronal apoptosis in a guinea pig animal model. Results indicate that chronic arsenic exposure caused a significant increase in ROS followed by NO and calcium influx. This calcium influx is mainly dependent on L-type voltage gated channels that disrupt mitochondrial membrane potential, increase bax/bcl2 levels and caspase 3 activity leading to apoptosis. Interestingly, blocking of ROS could completely reduce calcium influx whereas calcium blockage partially reduced ROS increase. While in general mono- and combinational chelation therapies were effective in reversing arsenic induced alteration, combinational therapy of DMSA and MiADMSA was most effective. Our results provide evidence for the role of L-type calcium channels in regulating arsenic-induced calcium influx and DMSA+MiADMSA combinational therapy may be a better protocol than monotherapy in mitigating chronic arsenicosis. [Copyright &y& Elsevier]

Abstract: Aim: Reprogramming of somatic cells utilizing viral free methods provide a remarkable method to generate human induced pluripotent stem cells (hiPSCs) for regenerative medicine. In this study, we evaluate developmental ontogeny of cardiomyocytes following induced differentiation of hiPSCs. Main Methods: Fibroblasts were reprogrammed with episomal vectors to generate hiPSC and were subsequently differentiated to cardiomyocytes. Ontogenic development of cardiomyocytes was studied by real-time PCR. Key findings: Human iPSCs derived from episomal based vectors maintain classical pluripotency markers, generate teratomas and spontaneously differentiate into three germ layers in vitro. Cardiomyogenic induction of these hiPSCs efficiently generated cardiomyocytes. Ontogenic gene expression studies demonstrated that differentiation of cardiomyocytes was initiated by increased expression of mesodermal markers, followed by early cardiac committed markers, structural and ion channel genes. Furthermore, our correlation analysis of gene expression studies with human heart demonstrated that pivotal structural genes like cardiac troponin, actinin, myosin light chain maintained a high correlation with ion channel genes indicating coordinated activation of cardiac transcriptional machinery. Finally, microelectrode recordings show that these cardiomyocytes could respond aptly to pharmacologically active drugs. Cardiomyocytes showed a chronotropic response to isoproterenol, reduced Na+ influx with quinidine, prolongation of beating rate corrected field potential duration (cFPD) with E-4031 and reduced beating frequency and shortened cFPD with verapamil. Significance: Our study shows that viral free hiPSCs efficiently differentiate into cardiomyocytes with cardiac-specific molecular, structural, and functional properties that recapitulate developmental ontogeny of cardiogenesis. These results, coupled with the potential to generate patient-specific hiPSC lines hold great promise for the development of in vitro platform for drug pharmacogenomics; disease modeling and regenerative medicine. [Copyright &y& Elsevier]

Abstract: The ability of human embryonic stem (ES) cells to differentiate into the three germ layers has proposed its application in studying human developmental toxicity in vitro. In the current study we investigated if the prompted application could be utilized to evaluate the efficacy of a newly developed arsenic antidote, monoisoamyl dimercaptosuccinic acid (MiADMSA) against arsenic (III) and if the results obtained in vitro were in concordance with the animal model for studying developmental toxicity. On the basis of real time PCR (qRT-PCR) and cytotoxicity analysis of human embryoid bodies (EBs), we observed that arsenic (III) caused a significant down regulation of gene expression in all the three germ layers, which could be correlated with high mortality, visceral and skeletal defects in pups. Reversal of arsenic-induced dysfunctioning could be observed with concomitant treatment of MiADMSA in vitro and in vivo, indicating ES–EB model could provide toxicity information similar to in vivo model. IR spectroscopy further suggested that MiADMSA bind to arsenic to form adduct, which prevents arsenic from exerting its toxic effect in both models. To our knowledge this study provides first experimental evidence suggesting human ES cells could be utilized in studying the efficacy of drugs in a comparable manner with animal models. We conclude that the ES–EB model seems to be an effective, faster, cost effective method for predicting efficacy of a drug. [Copyright &y& Elsevier]

Abstract: Among rheological models for estimating the rate of dissipation of non-breaking waves in muddy seabeds, those representing viscoelastic and poroelastic behaviors are used widely. In that regard, the dependence of the wave attenuation coefficient derived from basic rheological representations of mud behavior is examined on a cursory basis. For wave attenuation due to viscoelastic muds, results based on a semi-analytical model incorporating the effects of typically thin mud layers are summarized. This and an existing model for poroelastic beds are tested against selective laboratory data. Relying on these tests, it is emphasized that fluid-like mud should be modeled as a viscoelastic fluid medium, and that only non-fluid beds can be modeled as poroelastic media. Mechanisms for energy dissipation depend on bed compactness specified by the solids volume fraction, porosity or density, and on a characteristic Péclet number defined in terms of particle size, permeability and wave frequency. Due to the role of the latter parameter, for simulation of wave attenuation the chosen rheological model for a bed of given compactness must be applicable over the expected range of wave frequency. [Copyright &y& Elsevier]

Abstract: Garlic is well known as a folk remedy for a variety of ailments since ancient times, however, very few studies are available suggesting its beneficial role against arsenic toxicity pertaining to its ability to eliminate arsenic from the blood and soft tissues and in reversal of arsenic-induced oxidative stress in affected tissues. The present study was planned to investigate the protective efficacy of aqueous garlic extract using two different doses on parameters suggestive of hepatic injury, tissue oxidative stress and mobilization of arsenic. Further, an attempt to understand the mechanism of arsenic in inducing hepatic apoptosis was also studied. Results of the present study suggested that arsenic administration in mice caused generation of reactive oxygen species (ROS) causing apoptosis through mitochondria-mediated pathway. The ROS generation in hepatic tissue reverted to normal values after co-administration of garlic extracts. The study provides significant evidence that garlic extracts contain strong anti-oxidant property which could be beneficial in preventing arsenic-induced toxicity in cells. However, further research is required to determine whether the results from animal studies are applicable to humans before garlic can be recommended as a putative agent against arsenic toxicity. [Copyright &y& Elsevier]

Abstract: This paper presents a technique of multi-objective optimization for Model Predictive Control (MPC) where the optimization has three levels of the objective function, in order of priority: handling constraints, maximizing economics, and maintaining control. The greatest weights are assigned dynamically to control or constraint variables that are predicted to be out of their limits. The weights assigned for economics have to out-weigh those assigned for control objectives. Control variables (CV) can be controlled at fixed targets or within one- or two-sided ranges around the targets. Manipulated Variables (MV) can have assigned targets too, which may be predefined values or current actual values. This MV functionality is extremely useful when economic objectives are not defined for some or all the MVs. To achieve this complex operation, handle process outputs predicted to go out of limits, and have a guaranteed solution for any condition, the technique makes use of the priority structure, penalties on slack variables, and redefinition of the constraint and control model. An engineering implementation of this approach is shown in the MPC embedded in an industrial control system. The optimization and control of a distillation column, the standard Shell heavy oil fractionator (HOF) problem, is adequately achieved with this MPC. [Copyright &y& Elsevier]

Abstract: There is growing evidence that metalloid-induced cell death in protozoan parasites is due to oxidative injury; however, the biochemical changes related to this event are not fully understood. Leishmania spp. demonstrated cross-resistance to two related metalloids, arsenic and antimony, and both metalloids induced cell death accompanied by cell shrinkage and DNA fragmentation that was preceded by an increase in reactive oxygen species. Both drugs caused mitochondrial dysfunction in terms of loss of membrane potential and a drop in ATP levels. Arsenic treatment resulted in an elevation of intracellular Ca2+ levels that did not occur with antimony exposure. Cellular glutathione level was reduced after antimony treatment but arsenic did not affect glutathione. Inhibition of Ca2+ influx during arsenic treatment reduced cell death, whereas supplementation of glutathione during antimony treatment rescued cell loss. Under iron-depleted conditions, the cytotoxic effects of arsenic and antimony did not occur and cell survival increased; in contrast, the presence of excess iron resulted in higher cell death. Therefore, this study provides a new possibility that iron can potentiate parasite death induced by metalloids like arsenic and antimony. In addition, an important observation is that the two similar metalloids produce toxicity by very different mechanisms. [Copyright &y& Elsevier]

Abstract: Monoisoamyl dimercaptosuccinic acid (MiADMSA), a vicinal thiol chelating agent and an analogue of a conventional metal chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA) has recently been gaining recognition to be more effective chelating agent than DMSA in mobilizing lead, mercury and arsenic. However, very little information is available on the toxicological properties of this chelator. In the present study, MiADMSA was administered to pregnant female rats from day 14 of gestation to day 21 of lactation at different doses through oral (p.o.) and intraperitoneal (i.p.) routes to examine the toxicity in the pups and dams. Results suggested that MiADMSA had no effect on period of gestation, litter-size, sex ratio, and viability and lactation. No skeletal defects were observed following the administration of the chelator. However, MiADMSA administration produced few signs of oxidative stress in dams particularly at the higher doses (100 and 200mg/kg) as evident from increased thiobarbituric acid reactive substances (TBARS) in RBCs and decrease in the δ-aminolevulinic acid dehydratase (ALAD) activity. Administration of MiADMSA also caused some alterations in the essential metal concentration in the soft tissues especially tissue copper loss in lactating mothers and pups, which would be of some concern. Apart from copper, changes were also observed in the tissue zinc concentrations in mothers and pups following MiADMSA administration. The study thus suggests that the chelator is relatively safe during late gestation and it does not cause any major alteration in the mothers and the developing pups. However, detailed studies with MiADMSA, post-toxic metal exposure in pregnant animals may provide useful information. [Copyright &y& Elsevier]

The dose dependent effects of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid (DMSA) (0.1, 0.3 and 0.5 mmol kg−1, intraperitoneally (i.p.) once daily for 5 days) to offset the characteristic biochemical, immunological, oxidative stress consequences and DNA damage (based on DNA fragmentation and comet assay) following sub-chronic administration of gallium arsenide and the mobilization of gallium and arsenic were examined. The effects of these chelators alone in normal animals too were examined on above-mentioned variables. Male Wistar rats were exposed to 10 mg kg−1, GaAs, orally once daily for 12 weeks and were administered DMSA or two of its monoesters (monoisoamyl or monomethyl) for 5 consecutive days. DMSA was used as a positive control. DMSA and its derivatives, when given alone, generally have no adverse effects on various parameters. After 5 days of chelation therapy in GaAs pre-exposed rats, MiADMSA was most effective in the reduction of inhibited blood δ-aminolevulinic acid dehydratase (ALAD) activity and zinc protoporphyrin level while, all three chelators effectively reduced urinary ALA excretion, compared to GaAs alone exposed rats. MiADMSA was also effective, particularly at a dose of 0.3 mmol kg−1, in enhancing the inhibited hepatic transaminase activities. Parameters indicative of oxidative stress responded less favorably to the chelation therapy, however, three chelators significantly restored the altered immunological variables. MiADMSA was relatively more effective than the other two chelators. GaAs produced significant DNA damage in the liver and kidneys and the chelation treatment had moderate but significant influence in reducing DNA damage. All three chelators significantly reduced arsenic concentration and, however, MiADMSA was more effective than the other two chelators in depleting arsenic concentration from blood and other soft tissues. A dose of 0.3 mmol kg−1 was found to be relatively better than the other two doses examined. Gallium contents of blood and soft tissues remained uninfluenced by the chelation therapy. Significant loss of copper after MiADMSA administration, however, is of concern and requires further exploration. Additionally, further studies are required for the choice of appropriate dose, duration of treatment and possible toxic/side effects. Keeping in view the promising role of MiADMSA in the treatment of GaAs poisoning, these data will be needed for the registration of this chelating agent as licensed drug for the treatment of gallium arsenide intoxication. [Copyright &y& Elsevier]

Aluminum, a known neurotoxic substance, has been suggested as a contributing factor in the pathogenesis of Alzheimer''s disease. Therapeutic efficacy of combined administration of citric acid (CA) and N-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA) was evaluated in decreasing blood and brain aluminum concentration and parameters indicative of hematological disorders and brain oxidative stress. Adult male wistar rats were exposed to drinking water containing 0.2% aluminum nitrate for 8 months and treated once daily for 5 consecutive days with CA (50 mg/kg, orally) or HEDTA (50 mg/kg, intraperitoneally) either individually or in combination. Aluminum exposure significantly inhibited blood δ-aminolevulinic acid dehydratase while increased zinc protoporphyrin confirming changed heme biosynthesis. Significant decrease in the level of glutathione S-transferase in various brain regions and an increase in whole brain thiobarbituric acid reactive substance, and oxidized glutathione (GSSG) levels were also observed. Glutathione peroxidase activity showed a significant increase in cerebellum of aluminum exposed rats. Most of the above parameters responded moderately to the individual treatment with CA and HEDTA, but significantly reduced blood and brain aluminum burden. However, more pronounced beneficial effects on some of the above described parameters were observed when CA and HEDTA were administered concomitantly. Blood and brain aluminum concentration however, showed no further decline on combined treatment over the individual effect with HEDTA or CA. We conclude that in order to achieve an optimum effect of chelation, combined administration of CA and HEDTA might be preferred. However, further work is needed before a final recommendation could be made. [Copyright &y& Elsevier]

To assess the Pediatric Vision Scanner (PVS), a handheld vision screening device designed to test for amblyopia and strabismus, in a general pediatric population. In this prospective study, trained research staff screened 300 eligible children 24-72 months of age with no known eye conditions for amblyopia and strabismus using the PVS. A pediatric ophthalmologist masked to PVS screening results then performed a comprehensive eye examination. Sensitivity and specificity of the PVS was calculated with a 95% confidence interval. Based on the gold standard eye examination, 6 children (2%) had amblyopia and/or strabismus. The PVS detected all 6 cases, yielding a sensitivity rate of 100% (95% CI, 54%-100%). The PVS referred 45 additional children (15%) who had normal ophthalmic findings, yielding a specificity rate of 85% (95% CI, 80%-89%). The median acquisition time for the PVS was 28 seconds. The PVS detected amblyopia with high sensitivity in a nonenriched pediatric population. The device would allow children with amblyopia and/or strabismus to be referred to an eye care specialist as early as 2 years old. Given its short acquisition time, the PVS can be implemented in a pediatric clinic with minimal impact on workflow. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively describe the prevalence of amblyogenic risk factors in the siblings of patients with accommodative esotropia. Methods: We examined 81 proband children with accommodative esotropia and 115 siblings ages 10 years or younger in our clinical practice. Criteria for significant ocular findings in siblings included any of the following: spherical refractive error ≥ +3.5 D in either eye; astigmatism in either eye ≥1.0 D or 1.5 D depending on the axis; anisometropia ≥1.5 D; and/or any strabismus. Results: In siblings, 42.6% (95% CI: 34.0%-51.7%) had significant ocular findings: strabismus, 14.8% (95% CI: 8.3%-21.3%); hyperopia ≥3.5 D, 23.5% (95% CI: 16.6%-32.1%); astigmatism ≥1 D or 1.5 D (depending on axis), 13.9% (95% CI: 8.7%-21.5%); and anisometropia ≥1.5 D, 7.0% (95% CI: 3.4%-13.3%). Conclusions: Siblings of children with accommodative esotropia have a high prevalence of amblyogenic risk factors. This study offers additional data and rationale for providing comprehensive eye exams for children with a family history of strabismus. [Copyright &y& Elsevier]

Ameliorative effects of few naturally occurring antioxidants like ascorbic acid (vitamin C), α-tocopherol (vitamin E) either alone or in combination with meso-2,3-dimercaptosuccinic acid (DMSA) or monoisoamyl DMSA (MiADMSA), on parameters indicative of oxidative stress in the liver, kidney, brain and blood of lead-exposed rats were studied. Male Wistar rats were exposed to 0.1% lead acetate in drinking water for 3 months and treated thereafter with DMSA or its analogue MiADMSA (50 mg/kg, intraperitoneally), either individually or in combination with vitamin E (5 mg/kg, intramuscularly) or vitamin C (25 mg/kg, orally) once daily for 5 days. The effects of these treatments in influencing the lead-induced alterations in haem synthesis pathway, hepatic, renal and brain oxidative stress and lead concentration from the soft tissues were investigated. Exposure to lead produced a significant inhibition of δ-aminolevulinic acid dehydratase (ALAD) activity from 8.44±0.26 in control animals to 1.76±0.32 in lead control, reduction in glutathione (GSH) from 3.56±0.14 to 2.57±0.25 and an increase in zinc protoporphyrin level from 62.0±3.9 to 170±10.7 in blood, suggesting altered haem synthesis pathway. Both the thiol chelators and the two vitamins were able to increase blood ALAD activity towards normal, however, GSH level responded favorably only to the two thiol chelators. The most prominent effect on blood ALAD activity was, however, observed when MiADMSA was co-administered with vitamin C (7.51±0.17). Lead exposure produced a significant depletion of hepatic GSH from 4.59±0.78 in control animals to 2.27±0.47 in lead controls and catalase activity from 100±3.4 to 22.1±0.25, while oxidized glutathione (GSSG; 0.34±0.05 to 2.05±0.25), thiobarbituric acid reactive substance (TBARS; 1.70±0.45 to 5.22±0.50) and glutathione peroxidase (GPx) levels (3.41±0.09 to 6.17±0.65) increased significantly, pointing to hepatic oxidative stress. Altered, reduced and oxidized GSH levels showed significant recovery after MiADMSA and DMSA administration while, vitamins E and C were effective in reducing GSSG and TBARS levels and increasing catalase activity. Administration of MiADMSA alone and the combined administration of vitamin C along with DMSA and MiADMSA were most effective in increasing hepatic GSH levels to 4.88±0.14, 4.09±0.12 and 4.30±0.06, respectively. Hepatic catalase also reached near normal level in animals co-administered vitamin C with DMSA or MiADMSA (82.5±4.5 and 84.2±3.5, respectively). Combined treatments with vitamins and the thiol chelators were also able to effectively reduce lead-induced decrease in renal catalase activity and increase in TBARS and GPx level. Combination therapy, however, was unable to provide an effective reversal in the altered parameters indicative of oxidative stress in different brain regions, except in catalase activity. The result also suggests a beneficial role of vitamin E when administered along with the thiol chelators (particularly with MiADMSA) in reducing body lead burden. Blood lead concentration was reduced from 13.3±0.11 in lead control to 0.3±0.01 in MiADMSA plus vitamin E-treated rats. Liver and kidney lead concentration also showed a most prominent decrease in MiADMSA plus vitamin E co-administered rats (5.29±0.16 to 0.63±0.02 and 14.1±0.21 to 1.51±0.13 in liver and kidney, respectively). These results thus suggest that vitamin C administration during chelation with DMSA/MiADMSA was significantly beneficial in reducing oxidative stress however, it had little or no additive effect on the depletion of lead compared with the effect of chelators alone. Thus, the co-administration of vitamin E during chelation treatment with DMSA or MiADMSA could be recommended for achieving optimum effects of chelation therapy. [Copyright &y& Elsevier]