Long-term real-world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all-trans retinoic acid without chemotherapy-a retrospective, single-centre study.

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high-risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate- and high-risk disease received a further 2 years of maintenance with ATRA, 6-mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow-up. The mean (SD) estimated 5-year event-free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5-year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long-term outcomes in the real-world setting.

A method for scoring 4-nitroquinoline 1-oxide-induced murine esophageal squamous neoplasia.

A mouse model for esophageal squamous cell carcinoma (ESCC) is induced by oral administration of the carcinogen 4-nitroquinoline 1-oxide (4-NQO). There is not an objective method for determining histopathologic severity of disease in this model. We aim to create a clearly defined and easily applied scoring system that can quantify the severity of 4-NQO-induced murine ESCC. Fifteen wild-type C57BL/6J mice were treated with 4-NQO for 8 (n = 8) or 16 (n = 7) weeks, while the rest (n = 9) were treated with vehicle, as 8 weeks of 4-NQO typically results in dysplasia and 16 weeks in carcinoma. We identified histologic abnormalities of the esophagus in this model and developed metrics to grade severity of dysplasia, papillomas, and invasion. Scores were then calculated using quantitative digitized image analysis for measuring depth and extent of each feature within the entire sample. Each feature was also assigned a weight based on its relation to cancer severity. Histology scores were significantly different in the three groups, suggesting that this method can discriminate dysplasia from carcinoma. This model can be applied to any mouse treated with 4-NQO.

Analysis of risk factors for early death in patients with acute promyelocytic leukaemia treated with arsenic trioxide.

To date, no specific studies have evaluated early death (ED) in patients with acute promyelocytic leukaemia (APL) homogeneously treated with arsenic trioxide induction therapy and investigated according to the white blood cell (WBC) count at onset. Such patients were retrospectively analysed in this study, including 314 patients with a WBC count ≤ 10 × 109/L (standard-risk (SR) group) and 144 with a WBC count > 10 × 109/L (high-risk (HR) group). The baseline clinical characteristics and risk factors for ED were compared between the two groups. The incidence of fibrinogen < 1.0 g/L and elevated serum uric acid, aspartate aminotransferase and creatinine levels were higher in the HR group than in the SR group (P = 0.001; P < 0.001; P < 0.001; P = 0.044, respectively). The ED rate was significantly higher in the HR group than in the SR group (29.17% vs. 10.83%, P < 0.001). The main cause of ED was bleeding, followed by infection and differentiation syndrome (DS) in the HR group, while it was bleeding, followed by DS and infection in the SR group. Male sex, age > 50 years old, and fibrinogen < 1.0 g/L were independent risk factors for ED in the SR group. Increased serum creatinine levels, decreased albumin levels, and fibrinogen < 1.0 g/L were independent risk factors for ED in the HR group. Overall, the incidence of ED was higher in the HR group, and the baseline clinical characteristics, causes, times, and predictors of ED in the HR group differed from those in the SR group.

Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia.

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.

Acute respiratory distress after exposure to chlorine dioxide-based disinfectant.

A hospital cleaner developed acute respiratory distress after working with a chlorine dioxide-based disinfectant. The content of chlorine dioxide in the product is below the limit that would require the product to be labelled as hazardous to health, but we show with a simple estimation that the relevant threshold limit values for chlorine dioxide in the working atmosphere may be exceeded under normal use of the product. This may have implications for risk assessment of the use of such chlorine dioxide-based disinfectants and may warrant stricter regulations for labelling these products.

Tooth discoloration and the effects of internal bleaching on the novel endodontic filling material SavDen® MTA.

BACKGROUND/PURPOSE: Mineral trioxide aggregate (MTA) was widely used in endodontic therapy as bioceramic material. Although MTA has high biocompatibility, it may lead to tooth discoloration. The aim of this study was to investigate the discoloration of two different bioceramic materials and the effects of internal bleaching. METHODS: Thirty single-canal mandibular premolars were extracted and randomly assigned to three groups (n = 10), white ProRoot® MTA, SavDen® MTA and a control group. Endodontic access opening, cleaning and shaping were performed, then the teeth were obturated using the two bioceramic materials. Tooth color was recorded at baseline, day 1, and 1, 2, 4, 6, 8, 12, 16, and 24 weeks after treatment. At the end of 24 weeks, sodium perborate was used to perform internal bleaching. Tooth color was recorded at 1, 2, and 6 weeks subsequently. Teeth were measured using a DeguDent® spectrophotometer, and data were transformed into Commission Internationale de l'Eclairage (CIE) L∗a∗b∗ system. RESULTS: Teeth treated with white ProRoot® MTA showed significant color change and decrease in L∗ value. Internal bleaching leaded to decrease of the ΔE∗ value for all three groups and increase in the L∗ value. There was no difference in tooth discoloration between SavDen® MTA and the control group after obturation and internal bleaching. CONCLUSION: In terms of visual perception, white ProRoot® MTA tends to cause black and blue discoloration. SavDen® MTA, formulated with calcium lactate gluconate, could be used to reduce tooth discoloration in endodontic treatment.

Tooth discoloration induced by the different phases of a calcium aluminate cement: One-year assessment.

OBJECTIVES: To assess the discoloration of teeth treated with the different phases of calcium aluminate cement (CAC), in comparison with the conventional CAC and mineral trioxide aggregate (MTA). MATERIALS AND METHODS: Fifty bovine incisors were prepared and filled. Two millimeters of the filling was removed to fabricate a cervical plug with the following cements (n=10): CA(CaO.Al2 O3 ); CA2 (CaO.2Al2 O3 ); C12 A7 (12CaO.7Al2 O3 ); CAC and MTA. The initial color measurement was performed and after 7, 15, 30, 45, 90, 180, and 365 days new color measurements were performed to determine the color (ΔE00 ), lightness (ΔL'), chroma (ΔC'), hue differences (ΔH'), and the whiteness index (WID ). RESULTS: ΔE00 was significant for groups (p = 0.036) and periods (p < 0.05). The greater ΔE00 was observed after 365 days for CAC (12.8). C12 A7 (7.2) had the smallest ΔE00 . ΔL' and ΔC' were significant for groups and periods (p < 0.05). ΔH' was significant for periods (p < 0.05). After 365 days, significant reduction in lightness was observed for all groups. For CA, CA2 , CAC, and MTA groups, the WID values decreased over time (p < 0.05). CONCLUSIONS: The tested cements changed the color behavior of the samples, resulting in greater teeth darkening over time. CLINICAL SIGNIFICANCE: There is no long-term study assessing the discoloration induced by the different phases of CAC.

Metal Oxide Nanoparticles: Evidence of Adverse Effects on the Male Reproductive System.

Metal oxide nanoparticles (MONPs) are inorganic materials that have become a valuable tool for many industrial sectors, especially in healthcare, due to their versatility, unique intrinsic properties, and relatively inexpensive production cost. As a consequence of their wide applications, human exposure to MONPs has increased dramatically. More recently, their use has become somehow controversial. On one hand, MONPs can interact with cellular macromolecules, which makes them useful platforms for diagnostic and therapeutic interventions. On the other hand, research suggests that these MONPs can cross the blood-testis barrier and accumulate in the testis. Although it has been demonstrated that some MONPs have protective effects on male germ cells, contradictory reports suggest that these nanoparticles compromise male fertility by interfering with spermatogenesis. In fact, in vitro and in vivo studies indicate that exposure to MONPs could induce the overproduction of reactive oxygen species, resulting in oxidative stress, which is the main suggested molecular mechanism that leads to germ cells' toxicity. The latter results in subsequent damage to proteins, cell membranes, and DNA, which ultimately may lead to the impairment of the male reproductive system. The present manuscript overviews the therapeutic potential of MONPs and their biomedical applications, followed by a critical view of their potential risks in mammalian male fertility, as suggested by recent scientific literature.

The effect of different calcium silicate-based pulp capping materials on tooth discoloration: an in vitro study.

BACKGROUND: Variation in the composition of calcium silicate-based pulp capping materials could influence the discoloration potential of some of these materials, thus affecting the color and aesthetic appearance of the coronal tooth structure. Furthermore, contact with blood if hemostasis is not fully achieved may enhance this discoloration for some materials. Therefore the aim of this study was to evaluate in vitro the color change of coronal tooth structure after placing various calcium silicate-based materials in the pulp chamber in the presence or absence of blood. MEHTODS: Maxillary extracted premolars (n = 144) were sectioned and the crowns were separated from the roots. Pulp chambers were prepared to a standard size and then the tested materials (GMTA Angelus, ProRoot WMTA, Biodentine, TheraCal, and TotalFill) were placed with saline or with blood. Color change was assessed by spectrophotometry; prior to and after material placement at different time intervals of 24 h, 1 week, 1 month, 3 months, and 6 months. Color change (ΔE) values were calculated and statistically analyzed. RESULTS: In the saline groups, Biodentine caused the least color change, while GMTA and WMTA caused the highest color change which were significantly different from the others (p < 0.001), TotalFill and TheraCal caused moderate changes. Adding blood increased the ΔE overall the tested materials to various degrees. Biodentine was the most affected by the blood, while MTA groups were the least affected, followed by TotalFill and then TheraCal. The increase in ΔE was significant over time up to 3 months, after which the increase was not significant. CONCLUSIONS: Overall, WMTA and GMTA caused the most severe discoloration. In saline, Biodentine caused the least discoloration, but it was the most affected by the presence of blood, although it still caused the least discoloration similar to that observed with TotatFill. TheraCal caused moderate discoloration but more than that caused by Biodentine and TotalFill.

Tooth Discoloration Induced by Different Calcium Silicate-Based Cements: A Two-Year Spectrophotometric and Photographic Evaluation in Vitro.

OBJECTIVE: Calcium silicate-based cements (CSCs) may lead to coronal staining in young permanent teeth over the time. The purpose of this study was to evaluate and compare the long-term tooth discoloration induced by different CSCs. STUDY DESIGN: Ninety freshly-extracted human molars were assigned randomly into 6 groups (n=15/group) according to the CSC used as a pulpotomy material: ProRoot MTA, MTA Angelus, NeoMTA, EndoSequence Putty, Biodentine and Negative control (No cement). The color was assessed at baseline, and thereafter at 3, 6, 12 and 24 months by using both a spectrophotometer and digital images taken with and without a cross-polarizing filter. The time-dependent changes in color (ΔE) were compared within and among groups using Analysis of Variance. RESULTS: Angelus MTA and ProRooT MTA showed severe coronal discoloration (p>0.05) starting at 3 months. ΔE values of NeoMTA, EndoSequence Bioceramic Putty and Biodentine were below the perceptibility threshold, with Biodentine showing greater ΔE values than NeoMTA and EndoSequence Putty in the absence of statistical significance (p>0.05). CONCLUSIONS: Discoloration elicited by CSCs may develop soon after placement, and continue to increase for up to two years. Angelus MTA and ProRooT MTA cannot be recommended for vital pulp therapies in the esthetic zone of young individuals.

Quantifying Coronal Permanent Tooth Discoloration Caused by Different Pulpotomy Materials.

INTRODUCTION: Bioceramic materials, gray and white mineral trioxide aggregate (GMTA, WMTA), have been shown to have high rates of success in various endodontic applications. A major drawback is their tendency to discolor teeth compared to Biodentine (BD), that has been claimed not to discolor teeth. The aim of this study was to compare tooth discoloration after applying different pulpotomy base materials (BD, GMTA and WMTA). STUDY DESIGN: Forty human incisors teeth were used in this study. Coronal access was achieved by a Tungsten Carbide drill, and the pulp chambers were accessed and chemo-mechanically debrided. Each material was placed in the pulp chamber, up to the cervical sectioning level. All specimens were incubated at 37°C and 100% humidity for three months and have been evaluated before the study and weekly. Color was assessed according to the CIE L*a*b* color space system. RESULTS: ΔE of all experimental groups (GMTA, WMTA and BD) were significantly different from the control group at all time points (P<0.05). Color changes in the GMTA and WMTA groups, had no statistically significant differences, but showed higher discoloration compared to BD group in the cervical part of the crown, since week 1 (P<0.05). WMTA group showed significant discoloration in the cervical part as of week 1 (P<0.05), and gradually increased over time (Figure 2). BD group showed no significantly discoloration over time. GMTA group showed the significant discoloration at week 1 and week 14 (P<0.05). CONCLUSIONS: both GMTA and WMTA pulpotomy materials may discolor tooth structure over time in an extracted permanent anterior tooth model. When choosing bioceramic pulpotomy material, BD may be preferable in esthetic area.

Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

Low-Dose Radiation Exposure with 56MnO2 Powder Changes Gene Expressions in the Testes and the Prostate in Rats.

To investigate the biological effects of internal exposure of radioactive 56MnO2 powder, the major radioisotope dust in the soil after atomic bomb explosions, on male reproductive function, the gene expression of the testes and the prostate was examined. Ten-week-old male Wistar rats were exposed to three doses of radioactive 56MnO2 powder (41-100 mGy in whole body doses), stable MnO2 powder, or external 60Co γ-rays (2 Gy). Animals were necropsied on Days 3 and 61 postexposure. The mRNA expressions of testicular marker protein genes and prostatic secretory protein genes were quantified by Q-RT-PCR. On Day 3 postexposure, the testicular gene expressions of steroidogenesis-related enzymes, Cyp17a1 and Hsd3b1, decreased in 56MnO2-exposed groups. Germ cell-specific Spag4 and Zpbp mRNA levels were also reduced. On postexposure Day 61, the Cyp11a1 gene expression became significantly reduced in the testes in the group exposed to the highest dose of 56MnO2, while another steroidogenesis-related StAR gene mRNA level reduced in the 60Co γ-rays group. There were no differences in Spag4 and Zpbp mRNA levels among groups on Day 61. No histopathological changes were observed in the testes in any group following exposure. Expression in the prostatic protein genes, including CRP1, KS3, and PSP94, significantly decreased in 56MnO2-exposed groups as well as in the 60Co γ-rays group on Day 61 postexposure. These data suggest that the internal exposure to 56MnO2 powder, at doses of less than 100 mGy, affected the gene expressions in the testis and the prostate, while 2 Gy of external γ-irradiation was less effective.

Comparative Effects of Particle Sizes of Cobalt Nanoparticles to Nine Biological Activities.

The differences in the toxicity of cobalt oxide nanoparticles (Co-NPs) of two different sizes were evaluated in the contexts of the activities of bacterial bioluminescence, xyl-lux gene, enzyme function and biosynthesis of ß-galactosidase, bacterial gene mutation, algal growth, and plant seed germination and root/shoot growth. Each size of Co-NP exhibited a different level of toxicity (sensitivity) in each biological activity. No revertant mutagenic ratio (greater than 2.0) of Salmonella typhimurium TA 98 was observed under the test conditions in the case of gene-mutation experiments. Overall, the inhibitory effects on all five bacterial bioassays were greater than those on algal growth, seed germination, and root growth. However, in all cases, the small Co-NPs showed statistically greater (total average about two times) toxicity than the large Co-NPs, except in shoot growth, which showed no observable inhibition. These findings demonstrate that particle size may be an important physical factor determining the fate of Co-NPs in the environment. Moreover, combinations of results based on various biological activities and physicochemical properties, rather than only a single activity and property, would better facilitate accurate assessment of NPs' toxicity in ecosystems.

Pre-application of dentin bonding agent prevents discoloration caused by mineral trioxide aggregate.

BACKGROUND: To evaluate tooth discoloration by newly developed calcium silicate-based materials, and to examine the pre-application of dentin bonding agent (DBA) for preventing discoloration caused by mineral trioxide aggregate (MTA). METHODS: The roots of 50 premolars were randomly divided into five groups (n = 10) and cavities were prepared from resected root surfaces. MTA was placed in the cavities of teeth belonging to the ProRoot MTA (MTA) and RetroMTA (RMTA) groups. For teeth belonging to the ProRoot + DBA (MTA-B) and RetroMTA + DBA (RMTA-B) groups, DBA was first applied to the cavities prior to the addition of MTA. Teeth in the control group were restored with composite resin only (i.e., without MTA). After 12 weeks, MTA was removed from the MTA and RMTA groups and bleaching agents were applied for 3 additional weeks. Color assessments were recorded at baseline, and 1, 4, and 12 weeks, as well as after bleaching. A one-way ANOVA was performed to assess the differences between the two types of MTAs and color changes following DBA pre-application in each MTA group. A p-value of < 0.05 was considered indicative of statistical significance. RESULTS: Following 12 weeks of MTA treatment, there was a significant difference between the discoloration in the MTA and RMTA groups (p < 0.05). However, no significant difference was observed between the RMTA and RMTA-B groups (p > 0.05). Following bleaching, the color changes (ΔE values) of the MTA group were not significantly different from those of the MTA-B group (p > 0.05). The difference of ΔE between the RMTA group after internal bleaching and the RMTA-B group was also not significant (p > 0.05). CONCLUSIONS: RetroMTA caused significantly less discoloration than ProRoot MTA. Pre-application of DBA reduced discoloration caused by ProRoot MTA. MTA discoloration was improved equally well between DBA pre-application and post-bleaching.

Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab.

The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m2 on day 1) added to high-risk patients (white blood cell count, >10 × 109/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

Antibiotics and chemical disease-control agents reduce innate disease resistance in crayfish.

The aquaculture industry has developed rapidly in recent years, and in China Crayfish Procambarus clarkii represent an important aquaculture fishery. However, bacterial and viral diseases are becoming an increasingly serious threat, causing considerable economic losses. Farmers use a large number of drugs and chemicals to destroy pathogenic microorganisms and to purify aquaculture water. The purpose of this study was to assess the effects of such drugs on crayfish immune systems. Five of the most commonly used fishery drugs and water treatment chemicals were analyzed: norfloxacin, calcium hypochlorite, quick lime, povidone iodine and copper sulfate. Crayfish immune activity tests revealed that total hemocytes counts, as well as the activities of phenoloxidase and superoxide dismutase, decreased following exposure to all five treatments. These treatments, especially calcium hypochlorite and norfloxacin, significantly enhanced hemocyte apoptosis in crayfish, regardless of disease status. Calcium hypochlorite, in particular, led to a significant decrease in the survival rates of crayfish infected with white spot syndrome virus or Vibrio alginolyticus. Our results indicate that water treatment and disease control compounds commonly used in aquaculture can reduce the innate immunity and therefore disease resistance of crayfish.

Arsenic trioxide at conventional dosage does not aggravate hemorrhage in the first-line treatment of adult acute promyelocytic leukemia.

OBJECTIVES: The arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) therapy has demonstrated a tremendous success in the first-line treatment of acute promyelocytic leukemia (APL). Actually, early death (ED) is currently thought as a major challenge in APL. ATO has been reported to inhibit platelet function in vitro, and whether it increases the ED rate by exacerbating the hemorrhagic symptoms remains to be investigated. METHODS: Effects of ATO on platelet aggregation and adhesion were evaluated in vitro and in thirty-two complete remission (CR) and four newly diagnosed APL patients. Furthermore, concentrations of plasma total arsenic were monitored in APL patients via ICP-MS. RESULTS: The inhibition of platelet function, either aggregation or adhesion, did occur in vitro when the concentration of ATO reached 2 µmol/L. However, in CR APL patients receiving ATO with normal platelet count, the platelets responded normally when being activated and so did those in the newly diagnosed patients with thrombocytopenia. Our data further showed that the conventional dosage of ATO reached a plasma concentration substantially below the required concentration to inhibit platelets. CONCLUSIONS: In the first-line treatment of APL, the use of ATO is safe and effective and does not compromise the hemostatic potential that may eventually increase ED rate.

Ellagic acid mitigates arsenic-trioxide-induced mitochondrial dysfunction and cytotoxicity in SH-SY5Y cells.

In the current study, neuroprotective significance of ellagic acid (EA, a polyohenol) was explored by primarily studying its antioxidant and antiapoptotic potential against arsenic trioxide (As2 O3 )-induced toxicity in SH-SY5Y human neuroblastoma cell lines. The mitigatory effects of EA with particular reference to cell viability and cytotoxicity, the generation of reactive oxygen species, DNA damage, and mitochondrial dynamics were studied. Pretreatment of SH-SY5Y cells with EA (10 and 20 µM) for 60 min followed by exposure to 2 µM As2 O3 protected the SH-SY5Y cells against the harmful effects of the second. Also, EA pre-treated groups expressed improved viability, repaired DNA, reduced free radical generation, and maintained altered mitochondrial membrane potential than those exposed to As2 O3 alone. EA supplementation also inhibited As2 O3 -induced cytochrome c expression that is an important hallmark for determining mitochondrial dynamics. Thus, the current investigations are more convinced for EA as a promising candidate in modulating As2 O3 -induced mitochondria-mediated neuronal toxicity under in vitro system.

Risk factors for progression of chronic kidney disease in the EPPIC trials and the effect of AST-120.

BACKGROUND: Two randomized, double-blind, placebo-controlled trials (EPPIC-1 and EPPIC-2) investigated the efficacy and safety of AST-120, an oral spherical carbon adsorbent, in adults with chronic kidney disease (CKD). While the benefit of adding AST-120 to standard therapy was not supported by these trials, we performed a post hoc analysis to focus on CKD progression and to determine the risk factors for the primary endpoint in the EPPIC trial population. METHODS: In the EPPIC trials, patients were randomly assigned 1:1 to treatment with AST-120 or placebo. The primary endpoint was a composite of dialysis initiation, kidney transplantation, or doubling of serum creatinine. The EPPIC trial pooled population was evaluated with the same statistical methods used for analysis of the primary and secondary efficacy endpoints. The trials were registered on ClinicalTrials.gov (NCT00500682 [EPPIC-1] and NCT00501046 [EPPIC-2]). RESULTS: An analysis of the placebo population suggested baseline urinary protein to urinary creatinine ratio (UP/UCr) ≥1.0 and hematuria were independent risk factors for event occurrence and eGFR lowering. Analysis of the high risk patients revealed a difference in the primary endpoint occurrence between treatment groups, if angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers were administered (hazard ratio 0.74, 95% confidence interval 0.56-0.96). Also, the eGFR changes from baseline in the AST-120 group were smaller than that in the placebo group (P = 0.035). CONCLUSIONS: CKD progression may have an association with baseline UP/UCr and hematuria. Treatment with AST-120 may delay the time to the primary endpoint in patients with progressive CKD receiving standard therapy, thus warranting further investigation.