Oral administration of TiO2 nanoparticles during early life impacts cardiac and neurobehavioral performance and metabolite profile in an age- and sex-related manner.

BACKGROUND: Nanoparticles (NPs) are increasingly incorporated in everyday products. To investigate the effects of early life exposure to orally ingested TiO2 NP, male and female Sprague-Dawley rat pups received four consecutive daily doses of 10 mg/kg body weight TiO2 NP (diameter: 21 ± 5 nm) or vehicle control (water) by gavage at three different pre-weaning ages: postnatal day (PND) 2-5, PND 7-10, or PND 17-20. Cardiac assessment and basic neurobehavioral tests (locomotor activity, rotarod, and acoustic startle) were conducted on PND 20. Pups were sacrificed at PND 21. Select tissues were collected, weighed, processed for neurotransmitter and metabolomics analyses. RESULTS: Heart rate was found to be significantly decreased in female pups when dosed between PND 7-10 and PND 17-20. Females dosed between PND 2-5 showed decrease acoustic startle response and when dosed between PND 7-10 showed decreased performance in the rotarod test and increased locomotor activity. Male pups dosed between PND 17-20 showed decreased locomotor activity. The concentrations of neurotransmitters and related metabolites in brain tissue and the metabolomic profile of plasma were impacted by TiO2 NP administration for all dose groups. Metabolomic pathways perturbed by TiO2 NP administration included pathways involved in amino acid and lipid metabolism. CONCLUSION: Oral administration of TiO2 NP to rat pups impacted basic cardiac and neurobehavioral performance, neurotransmitters and related metabolites concentrations in brain tissue, and the biochemical profiles of plasma. The findings suggested that female pups were more likely to experience adverse outcome following early life exposure to oral TiO2 NP than male pups. Collectively the data from this exploratory study suggest oral administration of TiO2 NP cause adverse biological effects in an age- and sex-related manner, emphasizing the need to understand the short- and long-term effects of early life exposure to TiO2 NP.

The common indoor air pollutant α-pinene is metabolised to a genotoxic metabolite α-pinene oxide.

α-Pinene caused a concentration-responsive increase in bladder hyperplasia and decrease in sperm counts in rodents following inhalation exposure. Additionally, it formed a prospective reactive metabolite, α-pinene oxide.To provide human relevant context for data generated in animal models and explore potential mechanism, we undertook studies to investigate the metabolism of α-pinene to α-pinene oxide and mutagenicity of α-pinene and α-pinene oxide.α-Pinene oxide was formed in rat and human microsomes and hepatocytes with some species differences. Based on area under the concentration versus time curves, the formation of α-pinene oxide was up to 4-fold higher in rats than in humans.While rat microsomes cleared α-pinene oxide faster than human microsomes, the clearance of α-pinene oxide in hepatocytes was similar between species.α-Pinene was not mutagenic with or without induced rat liver S9 in Salmonella typhimurium or Escherichia coli when tested up to 10 000 µg/plate while α-pinene oxide was mutagenic at ≥25 µg/plate.α-Pinene was metabolised to α-pinene oxide under the conditions of the bacterial mutation assay although the concentration was approximately 3-fold lower than the lowest α-pinene oxide concentration that was positive in the assay, potentially explaining the lack of mutagenicity observed with α-pinene.

Toxicokinetic evaluation of the common indoor air pollutant, α-pinene, and its potential reactive metabolite, α-pinene oxide, following inhalation exposure in rodents.

The toxicokinetic behavior of α-pinene and its potential reactive metabolite, α-pinene oxide, was investigated following whole body inhalation exposure to 50 and 100 ppm α-pinene in rats and mice for 6 h per day for 7d. In both species and sexes, the maximum blood concentration (Cmax) increased more than proportionally while the increase in area under the concentration time curve (AUC) was proportional to the exposure concentration. When normalized to the calculated dose (D), both Cmax/D (male rats, 12.2-54.5; female rats, 17.4-74.1; male mice, 7.41-14.2; female mice, 6.59-13.0 (ng/mL)/(mg/kg)) and AUC/D (male rats, 28.9-31.1; female rats, 55.8-56.8; male mice, 18.1-19.4; female mice, 19.2-22.5 (h*ng/mL)/(mg/kg)) in rats were higher than in mice and in female rats were higher than in male rats; no sex difference was observed in mice. α-Pinene was eliminated from blood with half-lives between 12.2 and 17.4 h in rats and 6.18-19.4 h in mice. At the low dose, the ratio of α-pinene oxide to α-pinene, based on Cmax and AUC, respectively, was 0.200-0.237 and 0.279-0.615 in rats and 0.060-0.086 and 0.036-0.011 in mice demonstrating lower formation of the oxide in mice than in rats. At the high dose, the ratio decreased considerably in both species pointing to saturation of pathways leading to the formation of α-pinene oxide. α-Pinene and the oxide were quantified in the mammary glands of rats and mice with tissue to blood ratios of ≥23 demonstrating retention of these analytes in mammary glands. The findings of epoxide formation and species- and sex-differences in systemic exposure may be important in providing context and relating animal findings to human exposures.

Biodistribution, cardiac and neurobehavioral assessments, and neurotransmitter quantification in juvenile rats following oral administration of aluminum oxide nanoparticles.

Little is known about the uptake, biodistribution, and biological responses of nanoparticles (NPs) and their toxicity in developing animals. Here, male and female juvenile Sprague-Dawley rats received four consecutive daily doses of 10 mg/kg Al2 O3 NP (diameter: 24 nm [transmission electron microscope], hydrodynamic diameter: 148 nm) or vehicle control (water) by gavage between postnatal days (PNDs) 17-20. Basic neurobehavioral and cardiac assessments were performed on PND 20. Animals were sacrificed on PND 21, and selected tissues were collected, weighed, and processed for histopathology or neurotransmitter analysis. The biodistribution of Al2 O3 NP in tissue sections of the intestine, liver, spleen, kidney, and lymph nodes were evaluated using enhanced dark-field microscopy (EDM) and hyperspectral imaging (HSI). Liver-to-body weight ratio was significantly increased for male pups administered Al2 O3 NP compared with control. HSI suggested that Al2 O3 NP was more abundant in the duodenum and ileum tissue of the female pups compared with the male pups, whereas the abundance of NP was similar for males and females in the other tissues. The abundance of NP was higher in the liver compared with spleen, lymph nodes, and kidney. Homovanillic acid and norepinephrine concentrations in brain were significantly decreased following Al2 O3 NP administration in female and male pups, whereas 5-hydroxyindoleacetic acid was significantly increased in male pups. EDM/HSI indicates intestinal uptake of Al2 O3 NP following oral administration. Al2 O3 NP altered neurotransmitter/metabolite concentrations in juvenile rats' brain tissues. Together, these data suggest that orally administered Al2 O3 NP interferes with the brain biochemistry in both female and male pups.

Disposition and metabolism of sulfolane in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans.

Sulfolane has been found as a ground water contaminant near refining sites. These studies investigated the in vitro hepatic clearance and in vivo disposition of [14C]sulfolane in rats and mice following a single oral administration (30, 100, or 300 mg/kg) and dermal application (100 mg/kg).[14C]Sulfolane was well-absorbed in male rats following oral administration and excreted extensively in urine (≥93%). Total radioactivity in tissues at 24 and 48 h was ∼7% and <2%. Disposition pattern was similar in female rats and male and female mice at 100 mg/kg oral dose.Dermally applied [14C]Sulfolane (covered dose site, 100 mg/kg) was poorly absorbed in male (∼16%) and female (∼19%) rats; absorption increased to 59% when the dose site was uncovered in male rats suggesting ingestion of dose via grooming of the dose site. Dermally applied [14C]sulfolane (100 mg/kg, covered dose site) was well absorbed in male (∼70%) and female (∼80%) mice.Urinary radiochemical profiles were similar between routes, species, and sexes; the main analytes present in urine were sulfolane and 3-hydroxysulfolane.Sulfolane was not cleared in hepatocytes from rodents or human suggesting sites other than liver might be involved in metabolism of sulfolane in vivo.

Disposition and metabolism of antibacterial agent, triclocarban, in rodents; a species and route comparison.

Triclocarban is a residue-producing antibacterial agent used in a variety of consumer products. These studies investigated the disposition and metabolism of [14C]triclocarban. In male rats following a single gavage administration of 50, 150, and 500 mg/kg, excretion was primarily via feces (feces, 85-86%; urine, 3-6%) with no apparent dose-related effect. In male rats, 29% of the administered dose was excreted in bile suggesting some of the fecal excretion is from the absorbed dose which was excreted to the intestine via bile. The tissue retention of radioactivity was low in male rats (24 h, 3.9%; 72 h, 0.1%). Disposition pattern following gavage administration of 50 mg/kg in female rats and male and female mice were similar to male rats. Plasma elimination half-life of triclocarban in rats following gavage administration was shorter (∼2 h) compared to that based on total radioactivity (≥9 h) which included all products of triclocarban. Absorption following a single dermal application of 1.5 or 3% was low (≤3%) in rodents. Hydroxylated and conjugated metabolites of triclocarban predominated in bile. In hepatocytes, clearance of triclocarban in mouse and human was similar and was faster than in rat.

Optical direct intensity modulation of a 79GHz resonant tunneling diode-photodetector oscillator.

We report on the direct intensity modulation characteristics of a high-speed resonant tunneling diode-photodetector (RTD-PD) with an oscillation frequency of 79 GHz. This work demonstrates both electrical and optical modulation and shows that RTD-PD oscillators can be utilized as versatile optoelectronic/radio interfaces. This is the first demonstration of optical modulation of an RF carrier using integrated RTD-PD oscillators at microwave frequencies.

Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents: A dose, species, and sex comparison.

Sulfolane is a ground water contaminant near refinery sites. The objective of this work was to investigate the toxicokinetics and bioavailability of sulfolane in male and female Harlan Hsd:Sprague Dawley® SD® rats and B6C3F1/N mice following a single oral administration of 10, 30, or 100 mg/kg. Sulfolane was rapidly absorbed in rats with the maximum plasma concentration, Cmax, reached at ≤1.47 h. Although Cmax increased proportionally to the dose, the half-life of elimination increased with the dose and the area under the concentration versus time curve (AUC) increased more than proportionally to the dose. In male and female rats, plasma elimination half-life increased with the dose from 1.97 to 6.33 h. Absorption of sulfolane in mice following oral administration was more rapid than in rats with Cmax reached at ≤0.55 h. In addition, mice had a shorter half-life (≤ 1.25 h) and a lower AUC than rats. In male and female mice, both Cmax and AUC increased more than proportionally to the dose. Bioavailability of sulfolane was higher in rats (81-83%) than mice (59-63%) at 10 mg/kg; at 30 and 100 mg/kg, bioavailability >100% in both species and sexes suggesting that the saturation of metabolism and clearance processes of sulfolane may begin at a single oral dose of ~30 mg/kg. There was no apparent sex difference in toxicokinetic parameters of sulfolane in rats and mice. These data demonstrate that sulfolane was well-absorbed following oral administration with high bioavailability in rats and mice with some species differences, but no sex difference.

Disposition of tris(4-chlorophenyl)methanol and tris(4-chlorophenyl)methane in male and female Harlan Sprague Dawley rats and B6C3F1/N mice following oral and intravenous administration.

Tris(4-chlorophenyl)methane (TCPME) and tris(4-chlorophenyl)methanol (TCPMOH) have been detected in various biota and human tissues. The current studies were undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in rats and mice. [14C]TCPME was well absorbed (≥66%) in male rats and mice following a single oral administration of 1, 10, or 100 mg/kg. The excretion of [14C]TCPME-derived radioactivity in urine (≤2.5%) and feces (≤18%) was low. The administered dose was retained in tissues (≥ 64%) with adipose containing the highest concentrations. The metabolism of TCPME was minimal. The disposition and metabolism of [14C]TCPME in females was similar to males. The time to reach maximum concentration was ≤7 h, the plasma elimination half-life was ≥31 h, and the bioavailability was ≥82% following a 10 mg/kg oral dose of [14C]TCPME in male rats and mice. The disposition of [14C]TCPMOH was similar to that of [14C]TCPME. Following an intravenous administration of [14C]TCPME or [14C]TCPMOH in male rats and mice, the pattern of disposition was similar to that of oral administration. In conclusion, both TCPME and TCPMOH are readily absorbed and highly bioavailable following a single oral administration pointing to importance of assessing the toxicity of these chemicals.

Disposition and metabolism of the bisphenol analogue, bisphenol S, in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans.

With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500 mg/kg [14C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose. The disposition was similar in female rats and male and female mice following gavage administration. Radioactivity remaining in tissues at 72 h in both species and sexes was ≤2.4%. In bile duct cannulated rats 53% of a gavage dose was secreted in bile suggesting extensive enterohepatic recirculation of [14C]BPS. Following an intravenous dose in rats and mice, the pattern of excretion was similar to gavage. These data suggest that the dose excreted in feces folowing gavage administration is likely the absorbed dose. Urinary metabolites included the glucuronide and sulfate conjugates with a moderate amount of parent. The pattern of in vitro hepatic metabolsim was similar to in vivo with some difference among derivatives. These data suggest that similar to other bisphenol analogues, BPS was well absorbed following oral expsosure and extensively excreted with minimal tissue retention.

Disposition of [14C]hydroquinone in Harlan Sprague-Dawley rats and B6C3F1/N mice: species and route comparison.

1. Hydroquinone (HQ) is present in some foods and has varied industrial, medical and consumer uses. These studies were undertaken to investigate the disposition of HQ in rats and mice following gavage, intravenous (IV) and dermal exposure. 2. [14 C]HQ administered (0.5, 5 or 50 mg/kg) by gavage or IV routes to male and female Harlan Sprague-Dawley (HSD) rats and B6C3F1/N mice was well absorbed and rapidly excreted primarily in urine. Radioactivity remaining in tissues at 72 h was <1% for both species at all dose levels and routes. No sex, species or route related differences in disposition were found. 3. With dermal application of 2, 10 or 20% [14 C]HQ, mice absorbed higher percentages of the dose than rats (37, 12, 12% versus 18.6, 4.43 and 1.79%, respectively). The HQ mass absorbed by mice increased with dose, while in rats it was more constant over the dose range. Absorbed HQ was rapidly excreted in urine of both species and urinary excretion indicated continued absorption over the exposure period. No sex differences in disposition were found. 4. The oral bioavailability of HQ at 5 mg/kg was low in both rats (1.6%) and mice (3.9%) demonstrating significant first pass metabolism. Dermal bioavailability in mice was 9.4% following application of 2% formulation. 5. Urinary metabolites for both species and all routes included the glucuronide and sulfate conjugates; no parent was found in urine.

Metabolism and disposition of 2-ethylhexyl-p-methoxycinnamate following oral gavage and dermal exposure in Harlan Sprague Dawley rats and B6C3F1/N mice and in hepatocytes in vitro.

1. 2-Ethylhexyl-p-methoxycinnamate (EHMC) is commonly used as an ingredient in sunscreens, resulting in potential oral and dermal exposure in humans. 2. Clearance and metabolism of EHMC in hepatocytes and disposition and metabolism of EHMC in rodents following oral (8-800 mg/kg) intravenous (IV) (8 mg/kg) or dermal (0.8-80 mg/kg representing 0.1-10% formulation concentration) exposure to [14C]EHMC were investigated in rats and mice. 3. EHMC was rapidly cleared from rat and mouse hepatocytes (half-life ≤3.16 min) and less rapidly (half-life ≤48 min) from human hepatocytes. 4. [14C]EHMC was extensively absorbed and excreted primarily in urine by 72 h after oral administration to rats (65-80%) and mice (63-72%). Oral doses to rats were excreted to a lesser extent (3-8%) in feces and as CO2 (1-4%). Radioactive residues in tissues were <1% of the dose. There were no sex or species differences in disposition in rats. 5. Following dermal application, 34-42% of an 8-mg/kg dose was absorbed in rats, and 54-62% in mice in 72-h. 6. Among numerous urinary metabolites associated with hydrolysis of the ester, two potential reproductive and developmental toxicants, 2-ethylhexanol and 2-ethylhexanoic acid were produced by metabolism of EHMC.

Outcomes of Trabecular Metal-backed glenoid components in anatomic total shoulder arthroplasty.

BACKGROUND: As glenoid failure is one of the primary causes of failure of anatomic total shoulder arthroplasty (TSA), Trabecular Metal-backed glenoid components have become popular. This study reports implant survival and clinical outcomes of patients who received a Trabecular Metal-backed glenoid component during primary anatomic TSA. METHODS: Patients who underwent TSA with a Trabecular Metal-backed glenoid component by a single surgeon were identified and reviewed for clinical, radiographic, and patient-reported outcome measures with a minimum of 2 years' follow-up. RESULTS: Of 47 patients identified, radiographic and clinical follow-up was available on 36 patients (77%). Average age was 66.36 years (range, 50-85 years), and the average follow-up 41 months (range, 24-66 months). Three patients showed signs of osteolysis, 4 had radiographic evidence of metal debris, and 1 patient had a catastrophic failure after a fall. Of the 47 TSAs, 5 (11%) were revised to a reverse TSA for subscapularis failure and pain. Visual analog scale for pain scores improved by an average of 4.4. At final follow-up, the average Single Assessment Numeric Evaluation score was 72.4; Penn satisfaction score, 7.5; Penn score, 70.35; and American Shoulder and Elbow Surgeons score, 69.23. Outcome scores were similar in the 7 patients with osteolysis or metal debris compared to those without. CONCLUSION: Trabecular Metal-backed glenoids had a 25% rate of radiographic metal debris and osteolysis at a minimum 2-year follow-up in this series with one catastrophic failure. This implant should be used with caution, and patients followed closely.

Nanoscale silicon substrate patterns from self-assembly of cylinder forming poly(styrene)-block-poly(dimethylsiloxane) block copolymer on silane functionalized surfaces.

Poly(styrene)-block-poly(dimethylsiloxane) (PS-b-PDMS) is an excellent block copolymer (BCP) system for self-assembly and inorganic template fabrication because of its high Flory-Huggins parameter (χ âˆ¼ 0.26) at room temperature in comparison to other BCPs, and high selective etch contrast between PS and PDMS block for nanopatterning. In this work, self-assembly in PS-b-PDMS BCP is achieved by combining hydroxyl-terminated poly(dimethylsiloxane) (PDMS-OH) brush surfaces with solvent vapor annealing. As an alternative to standard brush chemistry, we report a simple method based on the use of surfaces functionalized with silane-based self-assembled monolayers (SAMs). A solution-based approach to SAM formation was adopted in this investigation. The influence of the SAM-modified surfaces upon BCP films was compared with polymer brush-based surfaces. The cylinder forming PS-b-PDMS BCP and PDMS-OH polymer brush were synthesized by sequential living anionic polymerization. It was observed that silane SAMs provided the appropriate surface chemistry which, when combined with solvent annealing, led to microphase segregation in the BCP. It was also demonstrated that orientation of the PDMS cylinders may be controlled by judicious choice of the appropriate silane. The PDMS patterns were successfully used as an on-chip etch mask to transfer the BCP pattern to underlying silicon substrate with sub-25 nm silicon nanoscale features. This alternative SAM/BCP approach to nanopattern formation shows promising results, pertinent in the field of nanotechnology, and with much potential for application, such as in the fabrication of nanoimprint lithography stamps, nanofluidic devices or in narrow and multilevel interconnected lines.

Comparison of Outcomes 1 Year After Rotator Cuff Repair With and Without Concomitant Biceps Surgery.

PURPOSE: To compare the outcomes of patients who undergo a long head of the biceps (LHB) procedure (tenotomy or tenodesis) concomitant with rotator cuff repair (RCR) to those of patients who undergo isolated RCR. METHODS: Prospectively collected data were retrospectively reviewed on 80 patients, >18 years old, who underwent repair of a full-thickness rotator cuff tear and with 1-year patient-reported outcome scores collected June 2012 to March 2015. The exclusion criteria were concomitant procedures other than LHB tenotomy, tenodesis, or subacromial decompression; prior shoulder surgery; or other shoulder pathology. The 3 patient groups are as follows: RCR + tenotomy, RCR + tenodesis, and isolated RCR. The primary outcome measures were American Shoulder and Elbow Surgeons (ASES) score, Western Ontario Rotator Cuff (WORC) index, and visual analog scale (VAS) for pain. A t-test measured the mean improvement in LHB patients compared with isolated RCR patients and compared the LHB tenotomy and tenodesis groups. Stepwise linear progression used LHB tenotomy or tenodesis as the primary predictor. RESULTS: The biceps procedure group had more female patients (22 vs 7, P = .01); otherwise there were no significant baseline differences. The LHB procedure group had significantly worse baseline ASES scores (mean, 48.9 vs 58.7; P = .032). All RCR patients showed significant improvement in all 3 outcome measures. Patients who had either LHB tenotomy or tenodesis (n = 45) demonstrated significantly greater mean improvement in ASES (mean, 42.7 vs 23.8; P = .002), VAS (mean, 49.2 vs 35.7; P = .020), and WORC scores (mean, 928 vs 743; P = .029) at 1-year follow-up compared with patients who had isolated RCR. ASES scores at 1 year were significantly better in the biceps group (91.6 vs 82.5; P = .023). Linear regression found a biceps procedure to be predictive of a significantly greater improvement in ASES score (P = .01). Analysis of variance revealed that both the LHB tenotomy (P = .04) and tenodesis (P = .01) groups demonstrated more favorable improvement in ASES when compared with RCR alone. CONCLUSIONS: Patients who underwent a concomitant biceps procedure when indicated at the time of RCR demonstrated inferior baseline patient-reported outcome measures and greater improvement after 1 year, as well as more favorable ASES scores at 1 year compared with isolated RCR patients. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Molecular Recognition-Mediated Transformation of Single-Chain Polymer Nanoparticles into Crosslinked Polymer Films.

We describe single-chain polymer nanoparticles (SCNPs) possessing intramolecular dynamic covalent crosslinks that can transform into polymer films through a molecular recognition-mediated crosslinking process. The SCNPs utilise molecular recognition with surface-immobilised proteins to concentrate upon a substrate, bringing the SCNPs into close spatial proximity with one another and allowing their dynamic covalent crosslinkers to undergo intra- to interpolymer chain crosslinking leading to the formation of polymeric film. SCNPs must possess both the capacity for specific molecular recognition and a dynamic nature to their intramolecular crosslinkers to form polymer films, and an investigation of the initial phase of film formation indicates it proceeds from features which form upon the surface then grow predominantly in the xy directions. This approach to polymer film formation presents a potential method to "wrap" surfaces displaying molecular recognition motifs-which could potentially include viral, cellular and bacterial surfaces or artificial surfaces displaying multivalent recognition motifs-within a layer of polymer film.

Metal-conductive polymer hybrid nanostructures: preparation and electrical properties of palladium-polyimidazole nanowires.

A simple, convenient method for the formation of hybrid metal/conductive polymer nanostructures is described. Polyimidazole (PIm) has been templated on λ-DNA via oxidative polymerisation of imidazole using FeCl3 to produce conductive PIm/DNA nanowires. The PIm/DNA nanowires were decorated with Pd (Pd/PIm/DNA) by electroless reduction of PdCl4(-2) with NaBH4 in the presence of PIm/DNA; the choice of imidazole was motivated by the potential Pd(II) binding site at the pyridinic N atom. The formation of PIm/DNA and the presence of metallic Pd on Pd/PIm/DNA nanowires were verified by FTIR, UV-vis and XPS spectroscopy techniques. AFM studies show that the nanowires have diameters in the range 5-45 nm with a slightly greater mean diameter (17.1 ± 0.75 nm) for the Pd-decorated nanowires than the PIm/DNA nanowires (14.5 ± 0.89 nm). After incubation for 24 h in the polymerisation solution, the PIm/DNA nanowires show a smooth, uniform morphology, which is retained after decoration with Pd. Using a combination of scanned conductance microscopy, conductive AFM and two-terminal measurements we show that both types of nanowire are conductive and that it is possible to discriminate different possible mechanisms of transport. The conductivity of the Pd/PIm/DNA nanowires, (0.1-1.4 S cm(-1)), is comparable to the PIm/DNA nanowires (0.37 ± 0.029 S cm(-1)). In addition, the conductance of Pd/PIm/DNA nanowires exhibits Arrhenius behaviour (E(a )= 0.43 ± 0.02 eV) as a function of temperature in contrast to simple Pd/DNA nanowires. These results indicate that although the Pd crystallites on Pd/PIm/DNA nanowires decorate the PIm polymer, the major current pathway is through the polymer rather than the Pd.

Dietary administration of diquat for 13 weeks does not result in a loss of dopaminergic neurons in the substantia nigra of C57BL/6J mice.

Male and female C57BL/6J mice were administered diquat dibromide (DQ∙Br2) in their diets at concentrations of 0 (control), 12.5 and 62.5 ppm for 13 weeks to assess the potential effects of DQ on the nigrostriatal dopaminergic system. Achieved dose levels at 62.5 ppm were 6.4 and 7.6 mg DQ (ion)/kg bw/day for males and females, respectively. A separate group of mice was administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ip as a positive control. The comparative effects of DQ and MPTP on the substantia nigra pars compacta (SNpc) and/or striatum were assessed using neurochemical, neuropathological and stereological endpoints. Morphological and stereological assessments were performed by investigators who were "blinded" to dose group. DQ had no effect on striatal dopamine concentration or dopamine turnover. There was no evidence of neuronal degeneration, astrocytic or microglial activation, or a reduction in the number of tyrosine hydroxylase positive (TH(+)) neurons in the SNpc or neuronal processes in the striatum of DQ-treated mice. These results are consistent with the rapid clearance of DQ from the brain following a single dose of radiolabeled DQ. In contrast, MPTP-treated mice exhibited decreased striatal dopamine concentration, reduced numbers of TH(+) neurons in the SNpc, and neuropathological changes, including neuronal necrosis, as well as astrocytic and microglial activation in the striatum and SNpc.

Click modification of diazido acridine intercalators: a versatile route towards decorated DNA nanostructures.

Diazido derivatives of 3,6-diamino acridine (proflavine) intercalate into DNA and undergo functionalization through click chemistry to form 1D nanostructures with redox active, conductive nanowire, and fluorescent properties. This two-step approach, intercalation followed by click modification allows for the controlled decoration of DNA nanostructures.