In vitro study of the effect of metabolism enzymes on benzo(a)pyrene-induced DNA damage in the scallop Chlamys farreri

Acute toxicity effect of benzo(a)pyrene (BaP) on isolated scallop (Chlamys farreri) digestive gland cells was studied and a dose-dependent increase in toxicity was observed. The 8 μg/L of BaP had a significant toxic effect on isolated cells (p < 0.05). In order to study the mechanism of CYP450, GST, SOD and MXR transporters involved in the production of DNA strand breakage such as DNA adduct formation and oxidative DNA damage by BaP were investigated in isolated digestive gland cells. Isolated cells were exposed in vitro to 0.8 μg/L of BaP for 24 h in the dark at 25 °C in the absence or presence of cytochrome P450 inhibitor, GST inhibitor, Pgp inhibitor and antioxidant enzyme inhibitor. DNA adduct and 8-OHdG content were measured using the Enzyme-linked Immunosorbent Assay. The result indicated that DNA strand breakage was increased to 2 times compared with the control in the 0.8 μg/L of BaP treatment groups. The BaP-induced DNA adduct and 8-OHdG content increased significantly by inhibiting GST, while only 8-OHdG increased significantly when SOD was inhibited. The content of DNA adduct and 8-OHdG had no significant change when CYP450 was inhibited, while it decreased significantly when MXR transporters were inhibited. The result proved that GST play a key role in eliminating the BaP-induced DNA adduct and 8-OHdG, and SOD also had an important function in reducing the production of BaP-induced 8-OHdG.     

Hesperidin,a citrus bioflavonoid,alleviates trichloroethylene-induced oxidative stress in Drosophila melanogaster

Trichloroethylene (TCE) is a chlorinated organic pollutant of groundwater with diverse toxic effects in animals and humans. Here, we investigated the ameliorative role of hesperidin, a citrus bioflavonoid on TCE-induced toxicity in Drosophila melanogaster. Four groups of D. melanogaster (50 flies/vial, with 5 vials/group) were exposed to ethanol (2.5%, control), HSP (400 mg/10 g diet), TCE (10 μM/10 g diet) and TCE (10 μM/10 g diet) + HSP (400 mg/10 g diet) respectively in the diet for 5 days. Then, selected oxidative stress and antioxidant markers were evaluated. The results showed that TCE significantly increased the level of reactive oxygen species (ROS) and inhibited catalase, glutathione S-transferase and acetylcholinesterase (AChE) activities with concurrent depletion of total thiol level. However, co-administration of TCE and hesperidin mitigated TCE-induced depletion of antioxidants, and restored ROS level and AChE activity in the flies (p < 0.05). Overall, hesperidin offered protective potency on TCE-induced oxidative stress in the flies via anti-oxidative mechanism.     

Impact of iron oxide nanoparticles on brain,heart, lung,liver and kidneys mitochondrial respiratory chain complexes activities and coupling

The present study evaluates the effects of iron oxide nanoparticles (ION) on mitochondrial respiratory chain complexes activities in five organs characterized by different oxidative capacities and strongly involved in body detoxification. Isolated mitochondria were extracted from brain, heart, lung, liver and kidneys in twelve Wistar rats (8 weeks) using differential centrifugations. Maximal oxidative capacities (Vmax), mitochondrial respiratory chain complexes activity using succinate (Vsucc, complexes II, III, and IV activities) or N, N, N′, N′-tetramethyl-p-phenylenediaminedihydrochloride (tmpd)/ascorbate (Vtmpd, complex IV activity) and, mitochondrial coupling (Vmax/Vo) were determined in controls and after exposure to 100, 200, 300 and 500 μg/ml Fe₃O₄. Data showed that baseline maximal oxidative capacities were 26.3 ± 4.7, 48.9 ± 4.6, 11.3 ± 1.3, 27.0 ± 2.5 and 13.4 ± 1.7 μmol O₂/min/g protein in brain, heart, lung, liver, and kidneys mitochondria, respectively. Complexes II, III, and IV activities also significantly differed between the five organs. Interestingly, as compared to baseline values and in all tissues examined, exposure to ION did not alter mitochondrial respiratory chain complexes activities whatever the nanoparticles (NPs) concentration used. Thus, ION did not show any toxicity on mitochondrial coupling and respiratory chain complexes I, II, III, and IV activities in these five major organs.     

The immune responses and expression of metallothionein (MT) gene and heat shock protein 70 (HSP 70) in juvenile rockfish,Sebastes schlegelii,exposed to waterborne arsenic (As3+)

Juvenile rockfish, Sebastes schlegelii (mean length 16.4 ± 1.9 cm, and mean weight 71.6 ± 6.4 g) were exposed for 20 days with the different levels of waterborne arsenic concentration (0, 50, 100, 200 and 400 μg/L). The plasma cortisol of S. schlegelii was significantly increased by the waterborne arsenit exposure. In the immune responses, the immunoglobulin M (Ig M) and lysozyme activity of S. schlegelii were significantly increased by the waterborne arsenic exposure. The acetylcholinesterase (AChE) activity of S. schlegelii was inhibited by the waterborne arsenic exposure. The substantial increases in the gene expression such as metallothionein (MT) and heat shock protein 70 (HSP 70) were observed by the waterborne arsenic exposure. The results demonstrated that waterborne arsenic exposure can induce the significant alterations in the immune responses and specific gene expression of S. schlegelii.     

Increased aquaglyceroporin 9 expression disrupts arsenic resistance in human lung cancer cells

Resistance to chemotherapy is one of the major problems in treatment responses of lung cancer. This study explored the mechanism underlying the arsenic resistance of lung cancer. Four lung cancer cells with different proliferation activity were characterized for cytotoxicity, arsenic influx/efflux, and arsenic effects on intracellular glutathione and 8-hydroxy-2′-deoxyguanosine (8-OHdG) production. Our data revealed that relative proliferation potency of these cells was H1299 > A549 > CL3 > H1355. Moreover, A549, H1299, and H1355 were markedly resistant to As₂O₃ with IC50 ≈ 100 μM, whereas CL3 was sensitive to As₂O₃ with IC50 ≈ 11.8 μM. After treatment with the respective As₂O₃ at IC50, arsenic influx/efflux activity in CL3 was comparable to those in the other three arsenic-resistant cells. However, differences in glutathione levels and 8-OHdG production were also detected either before or after arsenic treatment, indicating that a certain degree of variation in anti-oxidative systems and/or 8-OHdG repair activity existed in these cell lines. By transfection of an aquaglyceroporin 9 (AQP9) gene, we showed that increased AQP9 expression significantly enhanced arsenic uptake and disrupted arsenic resistance of A549. The present study strongly suggests that membrane transporters responsible for arsenic uptake, such as AQP9, may play a critical role in development of arsenic resistance in human lung cancer cells.     

Life-cycle exposure to BDE-47 results in thyroid endocrine disruption to adults and offsprings of zebrafish (Danio rerio)

2,2,4′,4′-Tetrabromodi-phenyl ether (BDE-47) is predominantly concentrated in humans and wildlife and disturbs thyroid hormone homeostasis. The purpose of this study was to characterize the thyroid endocrine disruption induced by life-cycle exposure to BDE-47 in adults and offspring of zebrafish (Danio rerio). We exposed zebrafish embryos at the blastula stage to different concentrations of BDE-47 (1, 5, and 10 μg/L). Exposure duration was 180 days until fish reached adulthood. In F0 larvae, exposure decreased survival and increased malformations at 4 dpf. Thyroid hormone concentrations did not differ significantly between the F0 larvae and controls. All exposures significantly up-regulated expression of tshß, pa8, ugt1 and tg and down-regulated ttr. Significant up-regulation of dio2 and crh was observed in the 10 μg/L BDE-47 group. There was no significant difference in the growth and somatic index between F0 adults and controls. BDE-47 (10 μg/L) significantly decreased whole-body content of thyroxine (T4) but significantly increased triiodothyronine (T3) in both sexes. All exposures up-regulated expression of crh, tshß, pa8, ugt1 and tg and down-regulated ttr. Exposure to 10 μg/L BDE-47 significantly up-regulated dio2 and ugt1 in both sexes. BDE-47 exposure (5 and 10 μg/L) significantly increased the activity of pethoxy-resorufin-O-deethylase and UDP-glucuronosyl transferase. BDE-47 (10 μg/L) significantly increased activity of ethoxy- and methoxy-resorufin-O-deethylase. In F1 offspring without continued BDE-47 (10 μg/L) treatment, T4 significantly decreased and T3 increased. T4 was further decreased and T3 was further increased with continued BDE-47 treatment. Continued BDE-47 exposure decreased hatching and increased malformation compared with those without BDE-47 exposure. Expression of crh, tshß, dio2, pa8, ugt1 and tg was significantly up-regulated without BDE-47 exposure and with continued exposure. With continued BDE-47 exposure, dio1 was significantly up-regulated and ttr was significantly down-regulated. All the genes showed clear differences between continued exposure to 10 μg/L BDE-47 and without BDE-47 exposure. These results suggest that parental exposure to BDE-47 results in thyroid endocrine disruption in adults and offspring.     

Disposition and acute toxicity of imidacloprid in female rats after single exposure

Single dose of imidacloprid (IMI-20 mg/kg bodyweight) was orally administered in female rats. Its disposition along with two metabolites 6-chloro nicotinic acid (6-CNA) and 6-hydroxy nicotinic acid (6-HNA) was monitored in organs (brain, liver, kidney, and ovary) and bodily fluids (blood, urine) at 6, 12, 24 and 48 h and faeces at 24 and 48 h. Maximum concentration (C_max) of IMI and metabolites in each organ and bodily fluid occurred after 12 h. Area under curve (AUC) of IMI ranged from 35 to 358 μg/ml/h; 6-CNA: 27.12–1006.42 μg/ml/h and 6-HNA: 14.98–302.74 μg/ml/h in different organs and bodily fluids. Clearance rate of IMI was maximum in ovary followed by kidney, liver, brain, faeces, blood and urine. Percent inhibition of acetyl-cholinesterase (AChE) was comparable in brain and Red Blood Cells (RBC) at 6–48 h which suggests the RBC-AChE as valid biomarker for assessing IMI exposure. It is evident that IMI was absorbed, metabolized, and excreted showing increased level of serum enzymes like Glutamic oxaloacetic transaminase (GOT), Glutamic pyruvic transaminase (GPT) and biochemical constituents like billirubin and Blood Urea Nitrogen (BUN) at 48 h. These data suggest that IMI is widely distributed, metabolized and induced toxicology effects at 20 mg/kg bodyweight to female rats.     

Juniperus oxycedrus L. subsp. oxycedrus and Juniperus oxycedrus L. subsp. macrocarpa (Sibth. & Sm.) Ball. “berries” from Turkey: Comparative evaluation of phenolic profile,antioxidant, cytotoxic and antimicrobial activities

This work aimed to evaluate and compare the phenolic profile and some biological properties of the ripe “berries” methanol extracts of Juniperus oxycedrus L. subsp. oxycedrus (Joo) and Juniperus oxycedrus L. subsp. macrocarpa (Sibth. & Sm.) Ball. (Jom) from Turkey. The total phenolic content resulted about 3-fold higher in Jom (17.89 ± 0.23 mg GAE/g extract) than in Joo (5.14 ± 0.06 mg GAE/g extract). The HPLC–DAD–ESI–MS analysis revealed a similar flavonoid fingerprint in Joo and Jom, whereas a difference in their quantitative content was found (4632 μg/g extract and 12644 μg/g extract). In addition, three phenolic acids were detected in Jom only (5765 μg/g extract), and protocatechuic acid was the most abundant one. The antioxidant capacity of the extracts was evaluated by different in vitro assays: in the DPPH and in the TBA tests a stronger activity in Jom was highlighted, while Joo exhibited higher reducing power and metal chelating activity. Joo and Jom did not affect HepG2 cell viability and both extracts resulted virtually non-toxic against Artemia salina. The extracts were also studied for their antimicrobial potential, displaying efficacy against Gram-positive bacteria.     

Chemistry and functional properties in prevention of neurodegenerative disorders of five Cistus species essential oils

The chemical composition of Cistus creticus, Cistus salvifolius, Cistus libanotis, Cistus monspeliensis and Cistus villosus essential oils has been examined by GC and GC–MS analysis. Height-nine constituents were identified in C. salvifolius oil, sixty in C. creticus, fifty-six in C. libanotis, fifty-four in C. villosus, forty-five in C. monspeliensis. Although the five species belong to the same genus, the composition showed interesting differences. Essential oils were screened also for their potential antioxidant effects (by DPPH, ABTS, FRAP and β-carotene bleaching test) and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, useful for prevention and treatment of Alzheimer’s disease. C. monspeliensis exhibited the most promising activity in β-carotene bleaching test (IC₅₀ of 54.7 μg/mL). In FRAP test C. libanotis showed a value of 19.2 μM Fe(II)/g. C. salvifolius showed the highest activity against AChE (IC₅₀ of 58.1 μg/mL) while C. libanotis, C. creticus, C. salvifolius demonstrated a good inhibitory activity against BChE with IC₅₀ values of 23.7, 29.1 and 34.2 μg/mL, respectively. Overall our results could promote the use of the essential oil of different Cistus species as food additives and for formulation of herbal infusion or nutraceutical products.     

Effect of prenatal manganese intoxication on [3H]glucose uptake in the brain of rats lesioned as neonates with 6-hydroxydopamine

In the present study we examined the effects of prenatal manganese (Mn) intoxication on [³H]glucose uptake in the brain of rats lesioned as neonates with 6-hydroxydopamine (6-OHDA). MnCl₂ ? 4H2O (10,000 ppm) was added to the drinking water of pregnant Wistar rats for the duration of pregnancy. On the day of parturition, Mn was discontinued as an additive to the drinking water. The control group consisted of rats that consumed water without Mn. Three days after birth, rats in both groups (control and Mn) were pretreated with desipramine hydrochloride (20 mg/kg) and pargyline hydrochloride (50 mg/kg) and injected bilaterally icv with one of three doses of 6-OHDAhydrobromide (15 μg, 30 μg or 67 μg base form in saline on each side) or with saline (control). 6-[³H]-Dglucose (500 μCi/kg, ip) was administered to male offspring in adulthood; after 15 min, brain specimens were taken (frontal cortex, hippocampus, striatum, thalamus with hypothalamus, pons and cerebellum) for determination of radioactivity in a liquid scintillation counter. Low dose 6-OHDA (15 μg icv) increased [³H]glucose uptake in all brain regions (p < 0.05) in both control and Mnintoxicated animals. In rats lesioned with a moderate dose of 6-OHDA(30 μg icv), [3H]glucose uptake was unaltered in both control and Mn-exposed rats. High dose 6-OHDA(67 μg icv) reduced [³H]glucose uptake in all brain regions of Mn-exposed rats (except for cerebellum) compared with the saline group (all, p < 0.05). There was no change in regional brain uptake of [³H]glucose in control rats. In conclusion, this study shows that mild neuronal insult (15 μg icv 6-OHDA) increased glucose uptake in the brain while severe damage (concomitant 60 μg icv 6-OHDA and Mn treatment) significantly diminished this process.     

Interaction of erythromycin and ketoconazole on the neurological,biochemical and behavioral responses in crucian carp

The presence of pharmaceuticals in the aquatic environment has received great attention due to their potential impacts on public health. The single, as well as the combined toxicities of erythromycin (ERY) and ketoconazole (KCZ) on the bioaccumulation, biochemical and behavioral responses, were examined in crucian carp. This study focused on the uptake of contaminants, acetylcholinesterase (AChE) activity in the brain, swimming and shoaling behavior of fish. After 14 days of binary exposure, the addition of KCZ at nominal concentrations of 0.2, 2 and 20 μg/L significantly increased the accumulation of ERY in the brain of the fish and the bioconcentration factor of 2.08 was 2.6-fold higher than that calculated from the ERY-alone exposure. The brain AChE activity was significantly inhibited by ERY and KCZ with a significant correlation with respect to the accumulative concentration of the contaminants. The inhibition rates of swimming activity to KCZ were increased with a corresponding increase in the exposure concentration of KCZ in the single exposure. However, this manner was altered by the combined exposure. In addition, shoaling was significantly enhanced by KCZ-alone exposure, which was significantly correlated with the swimming activity. This study indicates that the mixture of the contaminants may cause endocrine disrupting effects and behavior modification especially in fish with known ecological and evolutionary consequences.     

Genotoxicity and antileishmanial activity evaluation of Physalis angulata concentrated ethanolic extract

Antileishmanial in vitro tests, as well as Ames and micronucleus assays were performed with a concentrated ethanolic extract of Physalis angulata (EEPA)ResultsEEPA did not present mutagenic effect in Salmonella typhimurium strains at concentration reaching 3000 μg/plate and did not induce mutagenic effects after two oral administrations with a 24 h interval at a dose level of 2000 mg/kg. EEPA presented antileishmanial activity and presented an IC₅₀ value of 5.35 ± 2.50 μg/mL and 4.50 ± 1.17 μg/mL against Leishmania amazonensis and Leishmania braziliensis promastigotes, respectively. In the cytotoxicity test against macrophages, the EEPA had a LC₅₀ of 6.14 ± 0.59 μg/mL. Importantly, the IC₅₀ against L. amazonensis intracellular amastigotes was 1.23 ± 0.11 μg/mL.ConclusionEEPA extract is non-mutagenic and presented a promising pharmacological effect against Leishmania parasites.     

Methodological agreement on the in vitro activity of ceftaroline against cefotaxime-susceptible and -resistant pneumococci

Ceftaroline reportedly has lower minimum inhibitory concentrations (MICs) than established cephalosporins for Streptococcus pneumoniae. We further evaluated this activity using 155 pneumococci chosen by serotype and cefotaxime MIC. MICs were determined by agar dilution on Mueller–Hinton agar and Iso-Sensitest agar and by Etest. Inhibition zones were measured for 5 μg and 30 μg ceftaroline discs using both CLSI/EUCAST and BSAC methodology. Ceftaroline was more active than cefotaxime, with MICs 2–8-fold lower for isolates with cefotaxime MICs of ≤1 mg/L and mostly in the range 0.125–0.5 mg/L for those with cefotaxime MICs of 2 mg/L to ≥16 mg/L. Twelve isolates belonging to serotypes 14 (n = 2), 19A (n = 6) and 19F (n = 4) were ceftaroline-resistant, with MICs of 0.5–1 mg/L. Essential agreement between MIC methods was excellent, with values on Iso-Sensitest agar and Mueller–Hinton agar identical ±1 doubling dilution in all cases, and with 154/155 values identical ±1 doubling dilution between agar dilution and Etest. Nevertheless, 5/11 isolates with agar dilution MICs of 0.5 mg/L (i.e. just resistant) ‘had’ MICs of 0.25 mg/L (just susceptible) by Etest. Inhibition zones also correlated with MICs, but discrimination around the breakpoint MICs was poor irrespective of method and disc type. In summary, the results confirm the good activity of ceftaroline against pneumococci, but susceptibility testing will present challenges in routine laboratories, with discs poorly discriminatory and with Etest prone to give susceptible results for isolates with MICs one doubling dilution above the breakpoint.     

The herbicide glyphosate is a weak inhibitor of acetylcholinesterase in rats

The current work evaluated the inhibitory potency of the herbicide glyphosate (GLP) on acetylcholinesterase (AChE) activity in male and female rat tissues. The AChE activity in brain was higher (p < 0.05) than those observed in kidney (females: 2.2-fold; males: 1.9-fold), liver (females: 6-fold; males: 6.9-fold) and plasma (females: 14.7-fold; males: 25.3-fold). Enzyme activities were higher in presence of 10 mM GLP compared to those measured at an equimolar concentration of the potent AChE inhibitor dichlorvos (DDVP). Moreover, IC50s for GLP resulted between 6 × 10⁴- and 6.8 × 10⁵-fold higher than those observed for DDVP. In conclusion, GLP is a weak inhibitor of AChE in rats.     

Trends in and factors affecting the observed levels of urinary inorganic and total blood mercury among US children,adolescents, adults,and senior citizens over 2005–2012

Data from National Health and Nutrition Examination Survey (NHANES) for 2005–2012 were used to (i) study adjusted and unadjusted trends in the levels of urinary inorganic mercury (UIHG) and total blood mercury (TBHG) and (ii) factors that affect the observed levels of UIHG and TBHG among children aged 1–5 (CHLD15) and 6–11 (CHLD611) years, adolescents aged 12–19 years (ADOL), adults aged 20–64 years (ADLT), and senior citizens aged > = 65 years (SNR). Decrease in adjusted levels of UIHG for each 2-year NHANES cycle for CHLD611 was 0.08114 ng/L, 0.08379 ng/L for ADOLs, and 0.12 ng/L for ADLTs. Decreases in adjusted levels (AGM) of TBHG for each 2-year NHANES cycle were: 0.0632 ng/L for CHLD15, 0.10239 ng/L for CHLD611, 0.06424 ng/L for ADOLs, and 0.056088 ng/L for ADLTs. Among CHLD15 (0.34 vs. 0.39 μg/L, p < 0.01) and CHLD611 (0.42 vs. 0.44 μg/L, p = 0.04), males had lower AGMs for TBHG than females but among ADLTs (0.84 vs. 0.80 μg/L, p < 0.01) and SNRs (0.82 vs. 0.71 μg/L, p < 0.01) the reverse was true. For UIHG, for ADLTs (0.33 vs. 0.45 μg/L, p < 0.01) and SNRs (0.27 vs. 0.35 μg/L, p < 0.01) males had lower AGMs than females. Irrespective of age, those who were in unclassified race/ethnic group had the highest AGMs when compared with non-Hispanic whites, non-Hispanic blacks, and Mexican Americans and the differences, more often than not, were statistically significant (p < 0.01). Irrespective of age, fish and shellfish consumption during the last 30 days was associated with higher AGMs for both UIHG and TBHG than when fish and shellfish were not consumed and the differences were always statistically significant (p < 0.01). Nonsmoker ADLTs (0.86 vs. 0.78 μg/L, p < 0.01) and SNRs (0.83 vs. 0.71 μg/L, p < 0.01) were found to have higher adjusted levels of TBHG than smokers. It is hypothesized that constituents in tobacco smoke may accelerate excretion of mercury from the body.     

Investigation of the neuroprotective action of saffron (Crocus sativus L.) in aluminum-exposed adult mice through behavioral and neurobiochemical assessment

In the present study, the possible reversal effects of saffron against established aluminum (Al)-toxicity in adult mice, were investigated. Control, Al-treated (50 mg AlCl₃/kg/day diluted in the drinking water for 5 weeks) and Al + saffron (Al-treatment as previously plus 60 mg saffron extract/kg/day intraperitoneally for the last 6 days), groups of male Balb-c mice were used. We assessed learning/memory, the activity of acetylcholinesterase [AChE, salt-(SS)/detergent-soluble(DS) isoforms], butyrylcholinesterase (BuChE, SS/DS isoforms), monoamine oxidase (MAO-A, MAO-B), the levels of lipid peroxidation (MDA) and reduced glutathione (GSH), in whole brain and cerebellum. Brain Al was determined by atomic absorption spectrometry, while, for the first time, crocetin, the main active metabolite of saffron, was determined in brain after intraperitoneal saffron administration by HPLC. Al intake caused memory impairment, significant decrease of AChE and BuChE activity, activation of brain MAO isoforms but inhibition of cerebellar MAO-B, significant elevation of brain MDA and significant reduction of GSH content. Although saffron extract co-administration had no effect on cognitive performance of mice, it reversed significantly the Al-induced changes in MAO activity and the levels of MDA and GSH. AChE activity was further significantly decreased in cerebral tissues of Al + saffron group. The biochemical changes support the neuroprotective potential of saffron under toxicity.     

Antidermatitic Perspective of Hydrocortisone as Chitosan Nanocarriers: An Ex Vivo and In Vivo Assessment Using an NC/Nga Mouse Model

The aim of this study to administer hydrocortisone (HC) percutaneously in the form of polymeric nanoparticles (NPs) to alleviate its transcutaneous absorption, and to derive additional wound-healing benefits of chitosan. HC-loaded NPs had varied particle sizes, zeta potentials, and entrapment efficiencies, when drug-to-polymer mass ratios increased from 1:1 to 1:8. Ex vivo permeation analysis showed that the nanoparticulate formulation of HC significantly reduced corresponding flux [~24 μg/(cm² h)] and permeation coefficient (~4.8 × 10^? 3 cm/h) of HC across the full thickness NC/Nga mouse skin. The nanoparticulate formulation also exhibited a higher epidermal (1610 ± 42 μg/g of skin) and dermal (910 ± 46 μg/g of skin) accumulation of HC than those associated with control groups. An in vivo assessment using an NC/Nga mouse model further revealed that mice treated with the nanoparticulate system efficiently controlled transepidermal water loss [15 ± 2 g/(m² h)], erythema intensity (232 ± 12), dermatitis index (mild), and thickness of skin (456 ± 27 μm). Taken together, histopathological examination predicted that the nanoparticulate system showed a proficient anti-inflammatory and antifibrotic activity against atopic dermatitic (AD) lesions. Our results strongly suggest that HC-loaded NPs have promising potential for topical/transdermal delivery of glucocorticoids in the treatment of AD. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1063–1075, 2013     

The interactions of azure B,a metabolite of methylene blue,with acetylcholinesterase and butyrylcholinesterase

Methylene blue (MB) is reported to possess diverse pharmacological actions and is attracting increasing attention for the treatment of neurodegenerative disorders such as Alzheimer's disease. Among the pharmacological actions of MB, is the significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These activities may, at least in part, underlie MB's beneficial effects in Alzheimer's disease. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl metabolite, is the predominant species. Azure B has been shown to be pharmacologically active and also possesses a variety of biological actions. Azure B therefore may contribute to the pharmacological profile of MB. Based on these considerations, the present study investigates the possibility that azure B may, similar to MB, act as an inhibitor of human AChE and BuChE. The results document that azure B inhibits AChE and BuChE with IC₅₀ values of 0.486 μM and 1.99 μM, respectively. The results further show that azure B inhibits AChE and BuChE reversibly, and that the modes of inhibition are most likely competitive. Although the AChE and BuChE inhibitory activities of azure B are twofold and fivefold, respectively, less potent than those recorded for MB [IC₅₀(AChE) = 0.214 μM; IC₅₀(BuChE) = 0.389 μM] under identical conditions, azure B may be a contributor to MB's in vivo activation of the cholinergic system and beneficial effects in Alzheimer's disease.     

Manganese exposure through drinking water during pregnancy and size at birth: A prospective cohort study

The essential element manganese (Mn) might be toxic at excess exposure. We assessed the impact of elevated Mn exposure through drinking water during pregnancy on birth size in a population-based cohort(n = 1695) in rural Bangladesh. Concentrations of water Mn (median = 236 μg/L, range = 7.1–6336; n = 1177) and erythrocyte Mn (median = 30 μg/kg, range = 6.3–114; n = 758) were measured using ICP-MS. In regression analyses, newborns of women in the highest tertile of water Mn (median = 1495 μg/L) were 0.49 cm (0.20 SD) shorter (B = −0.42; 95% CI: −0.77, −0.08) than those in the lowest tertile (56 μg/L). The inverse association was significant in girls and also in boys of mothers with lowest hemoglobin values, likely due to higher absorption of Mn. Manganese concentrations in water and erythrocytes did not correlate, and the associations of the latter with birth size were less obvious. This study suggests that consumption of water with highly elevated Mn levels during pregnancy may impair fetal growth.