Protective Effect of Mesenchymal Stem Cell Active Factor Combined with Alhagi maurorum Extract on Ulcerative Colitis and the Underlying Mechanism.

Ulcerative colitis (UC) is a relapsing and reoccurring inflammatory bowel disease. The treatment effect of Alhagi maurorum and stem cell extracts on UC remains unclear. The aim of the present study was to investigate the protective role of Alhagi maurorum combined with stem cell extract on the intestinal mucosal barrier in an intestinal inflammation mouse model. Sixty mice were randomly divided into a control group, model group, Alhagi group, MSC group, and MSC/Alhagi group. MSC and Alhagi extract were found to reduce the disease activity index (DAI) scores in mice with colitis, alleviate weight loss, improve intestinal inflammation in mice (p < 0.05), preserve the integrity of the ileal wall and increase the number of goblet cells and mucin in colon tissues. Little inflammatory cell infiltration was observed in the Alhagi, MSC, or MSC/Alhagi groups, and the degree of inflammation was significantly alleviated compared with that in the model group. The distribution of PCNA and TNF-alpha in the colonic tissues of the model group was more disperse than that in the normal group (p < 0.05), and the fluorescence intensity was lower. After MSC/Alhagi intervention, PCNA and TNF-alpha were distributed along the cellular membrane in the MSC/Alhagi group (p < 0.05). Compared with that in the normal control group, the intensity was slightly reduced, but it was still stronger than that in the model group. In conclusion, MSC/Alhagi can alleviate inflammatory reactions in mouse colonic tissue, possibly by strengthening the protective effect of the intestinal mucosal barrier.

Resveratrol and lycium barbarum polysaccharide improve Qinling giant panda (Ailuropoda melanoleuca Qinlingensis) sperm quality during cryopreservation.

BACKGROUND: Semen cryopreservation has become an essential tool for conservation efforts of the giant panda (Ailuropoda melanoleuca); however, it is severely detrimental to sperm quality. Evidence has shown that antioxidants have the potential to reverse cryopreservation-induced damage in sperm. The purpose of this study was to screen effective antioxidants that could retain sperm quality during cryopreservation and to determine the optimal dose. Seven antioxidant groups, including resveratrol (RSV = 50 µM, RSV = 100 µM, RSV = 150 µM), lycium barbarum polysaccharide (LBP = 2 mg/mL, LBP = 4 mg/mL), laminaria japonica polysaccharides (LJP = 1 mg/mL) or combination (LBP = 2 mg/mL, LJP = 1 mg/mL and RSV = 100 µM) were assessed. RESULTS: RSV, LBP, LJP, or a combination of RSV, LBP, and LJP added to the freezing medium significantly improved sperm progressive motility, plasma membrane integrity, acrosome integrity, and mitochondrial activity during the cryopreservation process. Furthermore, the activities of glutathione peroxidase and superoxide dismutase were also improved. The levels of reactive oxygen species and malondialdehyde in semen were notably reduced. Hyaluronidase activity and acrosin activity were significantly increased in LBP-treated sperm. However, sperm total motility and DNA integrity were not significantly different between the groups. CONCLUSIONS: RSV (50 µM) or LBP (2 mg/mL) are the best candidate antioxidants for inclusion in the freezing medium to improve the quality of giant panda spermatozoa during semen cryopreservation.

FLCN regulates transferrin receptor 1 transport and iron homeostasis.

Birt-Hogg-Dubé (BHD) syndrome is a multiorgan disorder caused by inactivation of the folliculin (FLCN) protein. Previously, we identified FLCN as a binding protein of Rab11A, a key regulator of the endocytic recycling pathway. This finding implies that the abnormal localization of specific proteins whose transport requires the FLCN-Rab11A complex may contribute to BHD. Here, we used human kidney-derived HEK293 cells as a model, and we report that FLCN promotes the binding of Rab11A with transferrin receptor 1 (TfR1), which is required for iron uptake through continuous trafficking between the cell surface and the cytoplasm. Loss of FLCN attenuated the Rab11A-TfR1 interaction, resulting in delayed recycling transport of TfR1. This delay caused an iron deficiency condition that induced hypoxia-inducible factor (HIF) activity, which was reversed by iron supplementation. In a Drosophila model of BHD syndrome, we further demonstrated that the phenotype of BHD mutant larvae was substantially rescued by an iron-rich diet. These findings reveal a conserved function of FLCN in iron metabolism and may help to elucidate the mechanisms driving BHD syndrome.

Delisted routine eye examinations for nonrefractive eye conditions: a comparative analysis.

BACKGROUND: In 2004, Ontario delisted routine eye examinations for people aged 20-64 years, potentially encouraging patients seeking eye care to visit government-insured primary care providers (PCPs) rather than optometrists whose services had been deinsured. We investigated if utilization of PCP services for nonrefractive eye conditions increased after 2004 among Ontarians who were affected by the delisting. METHODS: We conducted a comparative analysis of the utilization of PCP services for nonrefractive eye conditions in Ontario using administrative data from 2000 to 2014. We included participants without a visit to government-insured optometrists or ophthalmologists in the year before the study year; we excluded participants with existing diabetes. Changes in utilization before and after delisting were statistically assessed using segmented regression analysis in subgroups stratified by age, sex, rurality and neighbourhood income. RESULTS: A significant increase in utilization of PCP services for nonrefractive ocular diagnoses after 2004 was documented among people affected by the delisting: 17.8% (95% confidence interval [CI] 17.0% to 18.7%) for people aged 20-39 years and 11.6% (95% CI 10.6% to 12.5%) for people aged 40-64 years. This corresponds to an increase in the number of patients who visited PCPs for nonrefractive ocular diagnoses of 10 690 (95% CI 321 to 21 059) for people aged 20-39 years and 20 682 (95% CI -94 to 41 457) for people aged 40-64 years. Among people aged 65 years and older (an age group not affected by the delisting), utilization of PCP services for nonrefractive ocular diagnoses was stable (p = 0.95) throughout the study period. Changes in utilization of PCP services for nonocular diagnoses were nonsignificant among people aged 0-19, 40-64 and 65 years and older. INTERPRETATION: After delisting, utilization of the services of government-funded PCPs for nonrefractive ocular diagnoses significantly increased among Ontarians affected by the delisting. The impact on ocular outcomes and the cost-effectiveness of increased use of PCPs for ocular management warrants further investigation and policy-makers' consideration.

Eye care utilisation in Newfoundland and Labrador: access barriers and vision health outcomes.

OBJECTIVE: Our prior study revealed significantly lower use of eye care providers in Newfoundland and Labrador (NFLD). This study reports factors associated with this low use and related vision health outcomes. DESIGN: Cross-sectional survey. PARTICIPANTS: A total of 14 925 Caucasian respondents to the Canadian Community Health Survey - Healthy Aging 2008/2009 aged ≥65 years. METHODS: Univariate and multivariate analyses were performed using self-reported survey data. RESULTS: NFLD, along with 3 other provinces, does not insure seniors for routine eye examinations. Among seniors without self-reported glaucoma, cataracts, and diabetes, the use of eye care providers in NFLD (36.3%) is the lowest compared with provinces with (50.7%, p < 0.05) and without (42.2%, p > 0.05) government-insured eye examinations. Among seniors with known eye disease insured for eye care in all provinces, eye care utilisation in NFLD (63.1%) is still the lowest across all provinces (69.4%-71.3%, p > 0.05). Compared with the national average, NFLD seniors have significantly higher proportions of low income (61.7% vs 47.4%), no postsecondary education (53.6% vs 42.2%), and rural residency (40.6% vs 18.9%). These factors are all associated with low levels of eye care utilisation. Compared with insured provinces, NFLD has a significantly lower prevalence of self-reported cataracts (16.7% vs 23.1) and glaucoma (3.8% vs 7.0%), and a slightly higher prevalence of presenting visual impairment (4.0% vs 3.5%). CONCLUSIONS: Lack of government insurance, low socioeconomic status, and living in nonurbanised areas all contribute to the underutilisation of eye care providers in NFLD. This underutilisation appears to be associated with reduced detection of eye diseases.

Socioeconomic status and utilization of amblyopia services at a tertiary pediatric hospital in Canada.

OBJECTIVE: To evaluate whether socioeconomic status is associated with equal utilization of amblyopia services at The Hospital for Sick Children (SickKids), a pediatric tertiary hospital in Canada. DESIGN: This is a retrospective, cross-sectional study. PARTICIPANTS: The medical records of children aged under 7 years diagnosed with amblyopia at SickKids from 2007 to 2009 were reviewed. METHODS: Socioeconomic status was derived from patients' residential postal codes through linking with income data in the 2006 Canadian census report. Patients were divided into 5 income quintiles to compare with amblyopia service utilization. The main outcome measure was the observed distribution of amblyopia patients by socioeconomic status versus the expected distribution of 20% for each quintile. RESULTS: The analyses included 336 patients. Children with amblyopia at SickKids were more likely to come from the richest neighbourhood (32.5%), whereas children from each of the 3 lowest quintiles (14.6%-15.5%) were less likely to present at SickKids. These results differed significantly from the expected 20% for each quintile (p < 0.0001). All types of amblyopia were significantly under-represented for children from the lower socioeconomic groups. When analyses were stratified by travel distance to the hospital, a significant inequality between the lower and higher income quintiles remained for nonmetropolitan Toronto patients, but not for metropolitan Toronto patients. CONCLUSION: Despite a publicly funded health-care system in Canada, children from lower socioeconomic neighbourhoods in distant areas utilize the amblyopia services in a tertiary pediatric centre less often than those from higher socioeconomic status.

Wait times and volume of cataract surgery in Ontario: 2000-2012.

OBJECTIVE: To review cataract surgery trends and wait times in Ontario. DESIGN: Retrospective analysis of health records. METHODS: Ontario Health Insurance Plan billing service claims between 2000 and 2012 were analyzed for the yearly number of cataract surgeries, alone and in combination with other procedures. The number of Ontarians with cataracts was estimated by applying composite prevalence curves derived from published population data. This was then used to calculate the yearly number of procedures per 1000 Ontarians with cataracts. RESULTS: Per 1000 people with cataract, the rate of cataract extraction increased 18.9% overall from 2000 to 2012, increasing by 38.3% from 2000 to 2006 and decreasing by 14.6% from 2006 to 2012. Mean wait times for cataract surgery decreased by 45.8% from 2006 to 2009 and increased 28.5% from 2009 to 2013. The proportion of surgeries that were same-day bilateral cataract extraction increased 2.21-fold from 2000 to 2012 but represented only 0.82% of total cataract surgeries in 2012. In 2000, 3% of cataract surgeries were combined with other procedures, and this decreased to 1.8% in 2012. Of these combinations, the rates of combined glaucoma filtration procedures decreased by 44.3%, anterior vitrectomy decreased by 32.5%, posterior vitrectomy increased by 58.3%, and corneal transplantation decreased by 10.7% during this time period. CONCLUSIONS: The yearly rate of cataract surgery has decreased since 2006, and wait times have increased from 2009. Same-day bilateral cataract extraction represented less than 1% of the total cataract surgical volume. Rates of cataract combined with posterior vitrectomy have increased (58%), whereas anterior vitrectomy at the time of cataract surgery decreased (33%).

Trends in glaucoma surgical procedures in Ontario: 1992-2012.

OBJECTIVE: To analyze trends in the surgical management of glaucoma in Ontario over the past 2 decades. DESIGN: Retrospective analysis of health records. METHODS: Ontario Health Insurance Plan billing service claims between 1992 and 2012 were analyzed for the yearly number of glaucoma laser and incisional surgical procedures. The yearly number of Ontarians with primary open-angle glaucoma (POAG) was estimated by applying composite prevalence curves to published population data and the yearly number of procedures per 1000 Ontarians with POAG was calculated. RESULTS: Per 1000 people with POAG, laser trabeculoplasty (LT) rates increased nearly 2-fold (185%) from 1992 to 2012, with the rates stabilizing between 2008 and 2012, and total glaucoma filtration procedure (GFP) rates (trabeculectomy, aqueous shunts, and combined GFP and cataract extraction) in 2012 were similar to those in 1992, with a peak rate noted in 1996. Shunts represented 0.9% of GFP in 1992 and 33% in 2012. Data for combination codes billed on the same day for the same patient were available from 2000. From 2000 to 2012 the rates of trabeculectomy alone remained unchanged, the number of aqueous shunts alone increased more than 5-fold, combined trabeculectomy and cataract extraction decreased 81%, whereas combined shunts and cataract extraction increased from 6 in 2000 to 420 in 2012. Combined aqueous shunts and cataract extraction represented 0.4% of combined cataract extractions in 2000 and 26.3% in 2012. CONCLUSIONS: Over the past 2 decades there was an overall increase in the rate of LT, no change in the rate of trabeculectomies, and a significant increase in aqueous shunt surgery.

Does government assistance improve utilization of eye care services by low-income individuals?

OBJECTIVE: To examine whether government-funded, low-income vision care programs improve use of eye care services by low-income individuals in Canada. DESIGN: Cross-sectional survey. PARTICIPANTS: 27,375 white respondents to the Canadian Community Health Survey (CCHS) Healthy Aging 2008/2009. METHODS: Government-funded, low-income vision care programs were reviewed. The amount of assistance provided was compared with professional fee schedules for general/routine eye examinations and market prices for eyeglasses. The utilization of eye care providers was derived from the CCHS. RESULTS: To receive low-income vision care assistance, individuals must be in receipt of social assistance. Criteria for receiving social assistance are stringent. The Canadian Financial Capability Survey revealed that 7.9% of Canadians aged 45 to 64 years and 5.5% aged ≥65 years received social assistance in 2009. The CCHS found in 2008/2009 that 12.5% of citizens aged 45 to 64 years and 13.2% of those aged ≥65 years had difficulty paying for basic expenses such as food. In 5 provinces, low-income vision care assistance fully covers a general/routine eye examination. In the remainder, the assistance provided is insufficient for a general/routine eye examination. The assistance for eyeglasses is inadequate in 5 provinces, requiring out-of-pocket copayments. Among middle-aged whites who self-reported not having glaucoma, cataracts, diabetes, or vision problems not corrected by lenses, utilization of eye care providers was 28.1% among those with financial difficulty versus 41.9% among those without (p < 0.05), giving a prevalence ratio 0.68 (95% CI 0.57-0.80) adjusted for age, sex and education. CONCLUSIONS: Despite government assistance, low-income individuals use vision care services less often than wealthy individuals.

Vitamin C supplementation enhances compact morulae formation but reduces the hatching blastocyst rate of bovine somatic cell nuclear transfer embryos.

Vitamin C, an antioxidant that reduces reactive oxygen species (ROS) in cells, is capable of significantly improving the developmental competence of porcine and mouse somatic cell nuclear transfer (SCNT) embryos, both in vitro and in vivo. In the present study, the effects of vitamin C on the developmental competence of bovine SCNT embryos were investigated. The results indicated that vitamin C (40 µg/mL) positively affected the scavenging of intracellular ROS, cleavage rate at 24 h (76.67 vs. 68.26%, p<0.05), compact morulae formation (60.83 vs. 51.30%, p<0.05), and the blastomere apoptosis index (3.70 ± 1.41 vs. 4.43% ± 1.65, p<0.05) of bovine SCNT embryos. However, vitamin C supplementation did not significantly affect the blastocyst formation rate and proportion of inner cell mass over total cells per blastocyst on day 7. Moreover, vitamin C supplementation obviously impaired the total cell numbers per blastocyst (97.20 ± 11.35 vs. 88.57 ± 10.43, p<0.05) on day 7 and the hatching blastocysts formation rate on day 9 (26.51 vs. 50.65%, p<0.05) compared with that of the untreated group. Vitamin C supplementation preferentially improved the viability of bovine SCNT embryos prior to the blastocyst stage, but did not enhance the formation and quality of blastocysts in vitro. In conclusion, the effect of vitamin C on the development of bovine SCNT embryos is complex, and vitamin C is not a suitable antioxidant chemical for the in vitro culture of bovine SCNT embryos.

In vitro potency and efficacy favor later generation fluoroquinolones for treatment of canine and feline Escherichia coli uropathogens in the United States.

Information regarding in vitro activity of newer fluoroquinolones (FQs) is limited despite increasing resistance in canine or feline pathogenic Escherichia coli (E. coli). This study describes in vitro potency and efficacy toward E. coli of seven FQs grouped according to similarities in chemical structure: enrofloxacin, ciprofloxacin, orbifloxacin (first-group), levofloxacin, marbofloxacin (second-group) and pradofloxacin, moxifloxacin (third-group; latest S, S-pyrrolidino-piperidine at C-7). Potency measures included minimum inhibitory concentration (MIC) (geometric mean MIC, MIC(50), MIC(90)); and mutant prevention concentration (MPC) for FQ susceptible isolates only. In vitro efficacy measures included relative susceptibility (MIC(BP-S):MIC) or resistance (MIC:MIC(BP-R)) and mutant selection window (MSW) (MPC:MIC). For enrofloxacin susceptible isolates, mean MIC (µg/ml) was least for each third-group drug and ciprofloxacin and greatest for enrofloxacin and orbifloxacin (P = 0.006). For enrofloxacin susceptible isolates, MPC were below MIC:MIC(BP-R) and least for pradofloxacin (0.29 ± 0.16 µg/ml) and greatest for enrofloxacin (1.55 ± 0.55 µg/ml) (P = 0.006). MSW was least for pradofloxacin (55 ± 30) and greatest for ciprofloxacin (152 ± 76) (P = 0.0024). MIC(BP-S):MIC was greatest (P = 0.025) for pradofloxacin (190.1 ± 0.61) and least for enrofloxacin (23.53 ± 0.83). For FQ susceptible isolates, FQs MIC:MIC(BP-R) may serve as a surrogate for MPC. Because in vitro efficacy was greatest for pradofloxacin; it might be preferred for treatment of urinary tract infections (UTIs) associated with FQ susceptible E. coli uropathogens.

De-insurance in Ontario has reduced use of eye care services by the socially disadvantaged.

OBJECTIVE: Effective November 1, 2004, the Ontario Ministry of Health and Long-Term Care de-insured, or delisted, routine eye examinations for Ontarians aged 20 to 64 years. We examined whether this delisting reduced Ontarians' access to eye care providers (ophthalmologists and optometrists). DESIGN: Cross-sectional survey. PARTICIPANTS: Ontario respondents to the Canadian Community Health Survey in 2000/2001 (n = 39 234 before delisting) and 2007/2008 (n = 43 835 after delisting). METHODS: We compared utilization rates of eye care providers by Ontarians in a 12-month period in 2000/2001 to utilization rates in 2007/2008 using self-reported data. RESULTS: Among Ontarians aged 40 to 64 years, utilization was significantly reduced (-7.2%, p < 0.05) after delisting by those who did not have a secondary school graduation certificate. This was compared to a slight reduction (-0.7%, p > 0.05) by those who had completed secondary school or higher education. A reduction of -5.4% was observed among Ontarians in the lowest income quintile in contrast to increased utilization in all other income groups (p > 0.05). Before delisting, the gap in utilization between people with and without a secondary school graduation certificate was 4.7%. This gap doubled to 11.2% after delisting (p < 0.05). The disparity in utilization between those in the highest and lowest income quintile was 4.5% before delisting and 12.0% after delisting (p > 0.05). Cost was the likely barrier that resulted in this finding. CONCLUSIONS: The use of eye care providers among socially disadvantaged Ontarians decreased significantly after vision care services were delisted. The effects of delisting appear to have caused an inequity in access to eye care providers, and that contradicts the objectives of the Canada Health Act.

Effect of local anesthesia on trabeculectomy success.

PURPOSE: To compare the long-term results of trabeculectomy surgery with subconjunctival anesthesia versus topical lidocaine 2% jelly. METHODS: A retrospective review of the long-term intraocular pressure (IOP) of 57 trabeculectomies previously enrolled in a prospective study comparing subconjunctival anesthesia to topical lidocaine 2% jelly. Baseline data included patient demographics, diagnosis, and ophthalmic history. Postoperative data included IOP, glaucoma therapy, and any interventions. Follow-up was conducted by reviewing the medical charts from July 2002 to August 2007. Differences between the groups were statistically assessed by the Student t test, chi(2) test, Fisher exact test, and Kaplan-Meier survival analysis. RESULTS: Data were available for 57 of the 58 original study patients, with a median age of 65 years. The median follow-up time was 4.2 years for both groups (range: 0.1 to 4.8). There were no statistically significant differences in baseline characteristics and follow-up observations. At the 4-year follow-up, 29.5% of the subconjunctival anesthesia patients versus 39.5% of the topical lidocaine 2% jelly patients were complete success (IOP between 6 to 21 mm Hg and 20% reduction without glaucoma therapy or repeat filtration surgery, P=0.15) and 82.7% of the subconjunctival anesthesia patients versus 95.8% for the topical lidocaine 2% jelly patients were qualified success (above with or without glaucoma therapy, P=0.39). CONCLUSIONS: Though small numbers observed, the 2 anesthetic techniques did not seem to influence the long-term success of trabeculectomy surgery. Further studies with more patients are warranted.

Selection of agents for prevention of cisplatin-induced hepatotoxicity.

The objective of this study was to explore the optimal combination of agents used along with cisplatin for protection of hepatotoxicity. Animal experiment was carried out based on the orthogonal design L(8) (2(7)) setting seven factors with two different levels of each, and eight groups of mice were needed. The agents tested in this study were zinc, selenium, fosfomycin, sodium thiosulfate (STS), N-acetyl-cysteine (NAC), methionine and taurine. Mice were supplemented by gavage with various combinations of agents as designed in the orthogonal table once a day for nine days beginning two days before cisplatin administration. 3.5mg/kg body weight of cisplatin was given intraperitoneally once a day for five days simultaneously. After cessation of cisplatin administration, the agents were supplemented continuously for two days. Activities of alanine aminotransferase (ALT) in serum, levels of glutathione (GSH) and malondialdehyde (MDA) in liver were analyzed after cessation of supplementation. Results showed zinc, fosfomycin and methionine were the effective factors for protection of weight loss; fosfomycin and methionine were the effective factors for prevention of decreased liver ratio; selenium, fosfomycin and STS were the effective factors for prevention of increased ALT activities in serum. On the other hand, methionine was the only effective factor for prevention of decreased GSH levels in liver; zinc, selenium and fosfomycin were the effective factors for prevention of increased MDA levels in liver. Based on the data observed in this study, the optimum combinations of agents were selenium, fosfomycin, methionine and taurine, and zinc, selenium, STS and methionine. In conclusion, each agent used in this study could play a beneficial role for prevention of cisplatin hepatotoxicity, however, none could play the crucial role. The potentiated actions for prevention of cisplatin hepatotoxicity could be achieved via combined use of these agents.

Effects of in utero meso-2,3-dimercaptosuccinic acid with calcium and ascorbic acid on lead-induced fetal development.

To examine the effects of meso-2,3-dimercaptosuccinic acid (DMSA) on developmental toxicity resulting from exposure to lead in utero, female albino mice were exposed to lead by drinking water contaminated with lead acetate for 4 weeks. After the cessation of lead exposure, female mice were supplemented by gavage with saline solution, DMSA, or DMSA and calcium as well as ascorbic acid from the fourth day of gestation until parturition, respectively. Lead levels (blood, liver, and bone) were measured at birth. Pups were then tested about neural development including surface righting reflex, cliff avoidance and air righting reflex. The markers of physical maturation, such as body weight, pinna unfolding, incisor eruption, and eye opening were also recorded. DMSA treatment decreased blood lead levels of pregnant mice, however, increased lead levels in both liver and bone of fetus, and delayed the early physical and neural development of offspring. Calcium and ascorbic acid reduced the transfer of lead to fetus. In conclusion, DMSA treatment during pregnancy enhances lead-induced fetal developmental toxicity.

Therapeutic potentials of combined use of DMSA with calcium and ascorbic acid in the treatment of mild to moderately lead intoxicated mice.

The aim of this study was to explore the therapeutic efficacies of combined use of meso-2,3-dimercaptosuccinic acid (DMSA) with calcium and ascorbic acid in the treatment of mild to moderately lead-intoxicated mice. Female albino mice were exposed to lead by drinking water contaminated with 0.1% (moderate lead exposure) or 0.05% (mild lead exposure) lead acetate. After the cessation of lead exposure, mice were supplemented by gavage with saline solution, 50 mg/kg body weight (b.w) DMSA, 100 mg/kg b.w DMSA, calcium and ascorbic acid, or 50 mg/kg b.w DMSA and calcium as well as ascorbic acid, respectively. Atomic absorption spectrophotometric method was used to analyze lead levels in blood, bone, liver, kidney and brain. Activities of blood delta-aminolevulinic acid dehydratase (ALAD) were determined by colorimetric method. DMSA supplemented alone could reduce lead levels in both soft tissues and bone and reverse lead-inhibited activities of blood ALAD in mild to moderately lead-intoxicated mice. On the other hand, combined use of DMSA with calcium and ascorbic acid achieved better therapeutic efficacies in mobilizing lead in blood, liver and kidney, and reversing lead-inhibited activities of blood ALAD in moderately lead intoxicated mice than DMSA supplemented alone. Moreover, the better therapeutic efficacies were also found in mildly lead intoxicated mice in mobilizing lead in blood and bone achieved by combined use of DMSA with calcium and ascorbic acid. Combined use of DMSA with calcium and ascorbic acid seems to be the better choice in the treatment of mild to moderate lead-intoxication.

Selection of micronutrients used along with DMSA in the treatment of moderately lead intoxicated mice.

The objective of this study was to explore the optimum combination of micronutrients used with 2,3-dimercaptosuccinic acid (DMSA) in the treatment of moderately lead-intoxicated mice. Experiment was carried out based on the orthogonal design L(8)(2(7)) setting six factors with two different levels of each, and eight groups of mice were needed. Mice were exposed to lead by drinking water contaminated with 0.1% lead acetate for four consecutive weeks, and then supplemented by gavage with different combinations of micronutrients with and without DMSA as designed in the orthogonal table. Lead levels in blood, liver, kidney, brain and bone and activities of blood delta-aminolevulinic acid dehydratase (ALAD) were analyzed after cessation of supplementation. The results suggested that DMSA was the only factor which could decrease significantly lead levels in blood, liver, kidney and bone; calcium and ascorbic acid were the notable factors decreasing lead levels in blood, liver, kidney, bone and brain; zinc and calcium were the notable factors reversing the lead-inhibited activities of blood ALAD; taurine was the notable factor decreasing lead levels in kidney and brain; and thiamine was the notable factor decreasing lead levels in brain. The lowest lead level in blood, liver, kidney and bone was shown in the mice supplemented with combination of calcium and ascorbic acid along with DMSA. In conclusion, the optimum combination of micronutrients used with DMSA suggested in present study was calcium and ascorbic acid, which seemed to potentiate the chelating efficacy of DMSA in the treatment of moderately lead intoxicated mice.