Low formalin concentrations induce fine-tuned responses that are sex and age-dependent : a developmental study

The formalin test is increasingly applied as a model of inflammatory pain using high formalin concentrations (5–15%). However, little is known about the effects of low formalin concentrations on related behavioural responses. To examine this, rat pups were subjected to various concentrations of formalin at four developmental stages: 7, 13, 22, and 82 days of age. At postnatal day (PND) 7, sex differences in flinching but not licking responses were observed with 0.5% formalin evoking higher flinching in males than in females. A dose response was evident in that 0.5% formalin also produced higher licking responses compared to 0.3% or 0.4% formalin. At PND 13, a concentration of 0.8% formalin evoked a biphasic response. At PND 22, a concentration of 1.1% evoked higher flinching and licking responses during the late phase (10–30 min) in both males and females. During the early phase (0–5 min), 1.1% evoked higher licking responses compared to 0.9% or 1% formalin. 1.1% formalin produced a biphasic response that was not evident with 0.9 or 1%. At PND 82, rats displayed a biphasic pattern in response to three formalin concentrations (1.25%, 1.75% and 2.25%) with the presence of an interphase for both 1.75% and 2.25% but not for 1.25%. These data suggest that low formalin concentrations induce fine-tuned responses that are not apparent with the high formalin concentration commonly used in the formalin test. These data also show that the developing nociceptive system is very sensitive to subtle changes in formalin concentrations.

Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with β-tricalcium phosphate microparticles (mPCL-TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL-TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.

The relationship between ambient ultraviolet radiation (UVR) and objectively measured personal UVR exposure dose is modified by season and latitude

Despite the widespread use of ambient ultraviolet radiation (UVR) as a proxy measure of personal exposure to UVR, the relationship between the two is not well-defined. This paper examines the effects of season and latitude on the relationship between ambient UVR and personal UVR exposure. We used data from the AusD Study, a multi-centre cross-sectional study among Australian adults (18-75 years), where personal UVR exposure was objectively measured using polysulphone dosimeters. Data were analysed for 991 participants from 4 Australian cities of different latitude: Townsville (19.3 °S), Brisbane (27.5 °S), Canberra (35.3 °S) and Hobart (42.8 °S). Daily personal UVR exposure varied from 0.01 to 21 Standard Erythemal Doses (median=1.1, IQR: 0.5–2.1), on average accounting for 5% of the total available ambient dose. There was an overall positive correlation between ambient UVR and personal UVR exposure (r=0.23, p<0.001). However, the correlations varied according to season and study location: from strong correlations in winter (r=0.50) and at high latitudes (Hobart, r=0.50; Canberra, r=0.39), to null or even slightly negative correlations, in summer (r=0.01) and at low latitudes (Townsville, r=-0.06; Brisbane, r=-0.16). Multiple regression models showed significant effect modification by season and location. Personal exposure fraction of total available ambient dose was highest in winter (7%) and amongst Hobart participants (7%) and lowest in summer (1%) and in Townsville (4%). These results suggest season and latitude modify the relationship between ambient UVR and personal UVR exposure. Ambient UVR may not be a good indicator for personal exposure dose under some circumstances.

Focal brachytherapy treatment planning using multi-parametric MRI and biological dose optimisation

We describe a novel approach to treatment planning for focal brachytherapy utilizing a biologically based inverse optimization algorithm and biological imaging to target an ablative dose at known regions of significant tumour burden and a lower, therapeutic dose to low risk regions.

LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion

Summary Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders. © 2015 The Authors.

Cytotoxicity of aluminium oxide nanoparticles towards fresh water algal isolate at low exposure concentrations

The growing commercial applications had brought aluminium oxide nanoparticles under,toxicologists' purview. In the present study, the cytotoxicity of two different sized aluminium oxide nanoparticles (ANP(1), mean hydrodynamic diameter 82.6 +/- 22 nm and ANP(2), mean hydrodynamic diameter 246.9 +/- 39 nm) towards freshwater algal isolate Chlorella ellipsoids at low exposure levels (<= 1 mu g/mL) using sterile lake water as the test medium was assessed. The dissolution of alumina nanoparticles and consequent contribution towards toxicity remained largely unexplored owing to its presumed insoluble nature. Herein, the leached Al3+ ion mediated toxicity has been studied along with direct particulate toxicity to bring out the dynamics of toxicity through colloidal stability, biochemical, spectroscopic and microscopic analyses. The mean hydrodynamic diameter increased with time both for ANP(1) 82.6 +/- 22 nm (0 h) to 246.3 +/- 59 nm (24h), to 1204 +/- 140 nm (72 h)] and ANP(2) 246.9 +/- 39 nm (Oh) to 368.28 +/- 48 nm (24 h), to 1225.96 +/- 186 nm (72 h)] signifying decreased relative abundance of submicron sized particles (<1000 nm). The detailed cytotoxicity assays showed a significant reduction in the viability dependent on dose and exposure. A significant increase in ROS and LDH levels were noted for both ANPs at 1 mu g/mL concentration. The zeta potential and FT-IR analyses suggested surface chemical interaction between nanoparticles and algal cells. The substantial morphological changes and cell wall damage were confirmed through microscopic analyses (SEM, TEM, and CLSM). At 72 h, significant Al3+ ion release in the test medium 0.092 mu g/mL for ANP(1), and 0.19 mu g/mL for ANP(2)] was noted, and the resulting suspension containing leached ions caused significant cytotoxicity, revealing a substantial ionic contribution. This study indicates that both the nano-size and ionic dissolution play a significant role in the cytotoxicity of ANPs towards freshwater algae, and the exposure period largely determines the prevalent mode of nano-toxicity.

High-resolution restoration of 3D structures from widefield images with extreme low signal-to-noise-ratio

Four-dimensional fluorescence microscopy-which records 3D image information as a function of time-provides an unbiased way of tracking dynamic behavior of subcellular components in living samples and capturing key events in complex macromolecular processes. Unfortunately, the combination of phototoxicity and photobleaching can severely limit the density or duration of sampling, thereby limiting the biological information that can be obtained. Although widefield microscopy provides a very light-efficient way of imaging, obtaining high-quality reconstructions requires deconvolution to remove optical aberrations. Unfortunately, most deconvolution methods perform very poorly at low signal-to-noise ratios, thereby requiring moderate photon doses to obtain acceptable resolution. We present a unique deconvolution method that combines an entropy-based regularization function with kernels that can exploit general spatial characteristics of the fluorescence image to push the required dose to extreme low levels, resulting in an enabling technology for high-resolution in vivo biological imaging.

Investigation of Mn-Implanted n-Si by Low-Energy Ion Beam Deposition

Mn ions were implanted to n-type Si(0 0 1) single crystal by low-energy ion beam deposition technique with an energy of 1000 eV and a dose of 7.5 x 10^{17} cm^{-2}. The samples were held at room temperature and at 300degreesC during implantation. Auger electron spectroscopy depth profiles of samples indicate that the Mn ions reach deeper in the sample implanted at 300degreesC than in the sample implanted at room temperature. X-ray diffraction measurements show that the structure of the sample implanted at room temperature is amorphous while that of the sample implanted at 300degreesC is crystallized. There are no new phases found except silicon both in the two samples. Atomic force microscopy images of samples indicate that the sample implanted at 300degreesC has island-like humps that cover the sample surface while there is no such kind of characteristic in the sample implanted at room temperature. The magnetic properties of samples were investigated by alternating gradient magnetometer (AGM). The sample implanted at 300degreesC shows ferromagnetic behavior at room temperature.

Mn implanted GaAs by low energy ion beam deposition

High dose Mn was implanted into semi-insulating GaAs substrate to fabricate embedded ferromagnetic Mn-Ga binary particles by mass-analyzed dual ion beam deposit system at room temperature. The properties of as-implanted and annealed samples were measured with X-ray diffraction, high-resolution X-ray diffraction to characterize the structural changes. New phase formed after high temperature annealing. Sample surface image was observed with atomic force microscopy. All the samples showed ferromagnetic behaviour at room temperature. There were some differences between the hysteresis loops of as-implanted and annealed samples as well as the cluster size of the latter was much larger than that of the former through the surface morphology. (C) 2004 Elsevier B.V. All rights reserved.

(Ga, Gd, As) film growth on GaAs substrate by low-energy ion-beam deposit

(Ga, Gd, As) film was fabricated by the mass-analyzed dual ion-beam epitaxy system with the energy of 1000 eV at room temperature. There was no new peak found except GaAs substrate peaks (0 0 2) and (0 0 4) by X-ray diffraction. Rocking curves were measured for symmetric (0 0 4) reflections to further yield the lattice mismatch information by employing double-crystal X-ray diffraction. The element distributions vary so much due to the ion dose difference from AES depth profiles. The sample surface morphology indicates oxidizing layer roughness is also relative to the Gd ion dose, which leads to islandlike feature appearing on the high-dose sample. One sample shows ferromagnetic behavior at room temperature. (C) 2003 Elsevier B.V. All rights reserved.

Low-loss planar and stripe waveguides in Nd3+-doped silicate glass produced by oxygen-ion implantation

We report on the fabrication and characterization of low-loss planar and stripe waveguides in a Nd3+-doped glass by 6 MeV oxygen-ion implantation at a dose of 1x10(15) ions/cm(2). The dark mode spectroscopy of the planar waveguide was measured using a prism coupling arrangement. The refractive index profile of the planar waveguide was reconstructed from a code based on the reflectivity calculation method. The results indicate that a refractive index enhanced region as well as an optical barrier have been created after the ion beam processing. The near-field mode profiles of the stripe waveguide were obtained by an end-fire coupling arrangement, by which three quasitransverse electric modes were observed. After annealing, the propagation losses of the planar and stripe waveguides were reduced to be similar to 0.5 and similar to 1.8 dB/cm, respectively. (c) 2007 American Institute of Physics.

Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys

With advancing age, monkeys develop deficits in spatial working memory resembling those induced by lesions of the prefrontal cortex (PFC). Aged monkeys also exhibit marked loss of dopamine from the PFC, a transmitter known to be important for proper PFC cognitive function. Previous results suggest that D1 agonist treatment can improve spatial working memory abilities in aged monkeys. However, this research was limited by the use of drugs with either partial agonist actions or significant D2 receptor actions. In our study, the selective dopamine D1 receptor full agonists A77636 and SKF81297 were examined in aged monkeys for effects on the working memory functions of the PFC. Both compounds produced a significant, dose-related effect on delayed response performance without evidence of side effects: low doses improved performance although higher doses impaired or had no effect on performance. Both the improvement and impairment in performance were reversed by pretreatment with the D1 receptor antagonist, SCH23390. These findings are consistent with previous results demonstrating that there is a narrow range of D1 receptor stimulation for optimal PFC cognitive function, and suggest that very low doses of D1 receptor agonists may have cognitive-enhancing actions in the elderly.

Tissue distribution and depuration of the extracted hepatotoxic cyanotoxin microcystins in crucian carp (Carassius carassius) intraperitoneally injected at a sublethal dose

An acute toxicity experiment was conducted by intraperitoneal injection with a sublethal dose of extracted microcystins (MCs), 50 mu g MC-LR (where L = leucine and R = arginine) equivalent/kg body weight (BW), to examine tissue distribution and depuration of MCs in crucian carp (Carassius carassius). Liver to body weight ratio increased at 3, 12, 24, and 48 h postinjection compared with that at 0 h (p < 0.05). MC concentrations in various tissues and aquaria water were analyzed at 1, 3, 12, 24, 48, and 168 h postinjection using liquid chromatography coupled with mass spectrometry (LC-MS). The highest concentration of MCs (MC-RR + MC-LR) was found in blood, 2 -270 ng/g dry weight (DW), followed by heart (3 -100 ng/g DW) and kidney (13 -88 ng/g DW). MC levels were relatively low in liver, gonad, intestine, spleen, and brain. MC contents in gills, gallbladder, and muscle were below the limit of detection. Significant negative correlation was present between MC-RR concentration in blood and that in kidney, confirming that blood was important in the transportation of MC-RR to kidney for excretion. Rapid accumulation and slow degradation of MCs were observed in gonad, liver, intestine, spleen, and brain. Only 0.07% of injected MCs were detected in liver. The recovery of MCs in liver of crucian carp seemed to be dose dependent.

Effects of indium ion implantation on the total dose hardness of fully depleted SOI NMOSFET

In this work, we investigate the effects of the indium ion implantation towards the back-channel interface on the total dose hardness of the n-channel SOI MOSFET. The results show that the indium implant has slight impact on the normal threshold voltage while preserving low leakage current after irradiation. The advantage is attributed to the narrow as-implanted and postanneal profile of the indium implantation. Two-dimensional simulations have been used to understand the physical mechanisms of the effects.

Mn implanted GaAs by low energy ion beam deposition

High dose Mn was implanted into semi-insulating GaAs substrate to fabricate embedded ferromagnetic Mn-Ga binary particles by mass-analyzed dual ion beam deposit system at room temperature. The properties of as-implanted and annealed samples were measured with X-ray diffraction, high-resolution X-ray diffraction to characterize the structural changes. New phase formed after high temperature annealing. Sample surface image was observed with atomic force microscopy. All the samples showed ferromagnetic behaviour at room temperature. There were some differences between the hysteresis loops of as-implanted and annealed samples as well as the cluster size of the latter was much larger than that of the former through the surface morphology. (C) 2004 Elsevier B.V. All rights reserved.