Search

Records on 1043 young Angus heifer and bull progeny from 73 sires, measured for methane production in respiration chambers, were used to evaluate the accuracy of a 1-day measurement relative to 2-day measurement duration. The traits assessed were dry matter intake (DMI, kg/day), methane-production rate (MPR, g/day), methane yield (MY,MPR per unit DMI) and four residual methane (RMP, g/day) traits. The RMP traits were computed as actual MPR minus expected MPR, where the expected MPR were calculated from three widely used equations. The expected MPR for the fourth RMP trait was computed by regressing MPR on DMI, using the data from the study. Variance components, heritability, phenotypic and genetic correlations, and the efficiency of selection using 1-day compared with 2-day measurement were used as assessment criteria. The environmental variance for the 2-day measurement was slightly lower than that of the 1-day measurement for all the traits studied, indicating that the addition of an extra day of data was effective in reducing the amount of unexplained variation in each trait. However, these minor reductions did not have a major impact on accuracy; hence, very high phenotypic (rp of 0.91-0.99) and genetic (rg of 0.99 for each trait) correlations were obtained between the two measurement durations. The very high genetic correlation between the two durations of measurement indicated that, at the genetic level, the 1-day duration is measuring the same trait as the 2-day measurement duration. Any enteric-methane emission-abatement strategy that seeks to reduce MPR per se, may have a detrimental impact on ruminant productivity through a correlated reduction in feed intake; hence, MY and the RMP traits are likely to be the traits of interest for genetic improvement. Efficiency of selection for MY and the RMP traits ranged from 0.96 to 0.99, which implies that there would be less than 5% loss in efficiency by adopting a 1-day relative to a 2-day methane-measurement duration. While the throughput of the respiration-chamber facility can be increased by adopting a 1-day measurement duration, additional resources, such as holding pens, would be required to take advantage of the extra day. [ABSTRACT FROM AUTHOR]

The article presents a paper discussing dimensional variations in full-fashioned garments knitted from dyed yarns. T. Gardiner described the setting-up of the Production Advisory Service by a group of manufacturers with a view to increasing efficiency and reducing the number of sub-standard garments produced. The yarns they used were on cone and included lambs' wool, cashmere, botany and few synthetic fibers. A. M. Robertson dealt only with the dimensions that were determined by the machine on which the fiber was knitted.

An abstract of the article "BH4 Deficiency Reduces Vascular Repair in the Retina," by K. S. Edgar is and colleagues is presented.

Context: Cattle and sheep emit methane, a potent greenhouse gas, as part of the fermentation process of feed digestion in their gut; however, the mechanisms explaining differences among animals in enteric methane production are not fully understood. Aim: To investigate whether variation among animals in their ability to digest their test ration was associated with phenotypic and genetic variation in methane production. Methods: The experiment used 135 Angus beef cattle measured for their phenotypic and genetic merit for methane production. The extent of digestion of the dry matter (DMD) in the test ration by individual cattle was determined using silica as a naturally present indigestible marker. Its concentration in feed consumed and faeces was determined using rapid portable X-ray fluorescence spectroscopy, from which DMD was calculated. Key results: Higher daily methane-production rate (MPR), higher methane produced per unit of feed consumed (methane yield; MY) and higher methane produced than the predicted daily production (residual MPR; RMP) by animals was accompanied by higher DMD. Higher genetic merit for MPR was also accompanied by higher DMD, but DMD had no detectable association with genetic variation in the other two methane emission traits. The regression coefficients for change in MPR (g/day), MY (g/kg DMI), RMP (g/day) with change in DMD (%) were 2.6 ± 1.1 (s.e.; P < 0.05), 0.14 ± 0.07 (P < 0.1) and 0.68 ± 0.38 (P < 0.1) respectively. Conclusions: Differences among animals in their DMD were found and were associated with phenotypic variation in the three methane emission traits studied, and with genetic variation in daily methane production. The results support the caution that feeding and breeding interventions seeking to reduce methane emissions can also reduce the extent of digestion of feed by cattle. Implications: Feeding and breeding interventions that seek to reduce methane emissions may change rumen physiology and reduce the extent of digestion of feed by cattle, which may be undesirable. Cattle and sheep emit methane, a potent greenhouse gas, as part of the fermentation process of feed digestion. Differences among animals in their ability to digest feed were found and were associated with variation in the three methane emission traits studied. Feeding and breeding interventions to reduce methane emissions may change rumen physiology and reduce the extent of digestion of feed by cattle, which may be undesirable. [ABSTRACT FROM AUTHOR]

Vertical column abundances of HCl, ClONO2, HF and HNO3 have been obtained from infrared solar absorption measurements made at Aberdeen, UK (57 deg. N, 2 deg. W) during the periods January 13 1994-May 8 1994 and November 23 1994-April 19 1995. The measurements reveal the partitioning of inorganic chlorine (Cly)inside and outside the polar vortex during these two winter and spring periods. Stratospheric temperatures within the northern polar vortex during 1993/94 were not cold throughout January and most of February. The measurements reported here suggest that following a brief period of chlorine activation in late February and early March, the active chlorine within the vortex recovered rapidly to form ClONO2 resulting in in-vortex ClONO2 columns of 7 x 1015 molecules cm-2. In contrast, measurements during January 1995 suggest extensive in-vortex activation with in-vortex HCl+ ClONO2 as low as 3.6 x 1015 molecules cm-2. High day-to-day variability in the ClONO2 columns observed during February is evidence for the transport of ClONO2 rich air from high to mid latitudes during the late winter.The implications for mid latitude O3 loss are discussed. A preliminary comparison of the HCl, ClONO2, and HNO3 column data from winter 1994/95 with a three-dimensional chemical transport model shows that the model generally reproduces well the day-to-day variability and absolute magnitude of the observed columns, especially for HNO3 outside the vortex. [ABSTRACT FROM AUTHOR]

We outline how ground-based Fourier transform infrared (FTIR) measurements of stratospheric trace species, obtained with high temporal resolution, could be used to detect filaments of polar vortex air at mid-latitudes and therefore test high spatial resolution chemical transport models (CTMs). Vertical column abundances of HCl, ClONO2, HNO3, N2O and HF have been obtained from FTIR solar absorption measurements made throughout the day from Aberdeen, UK (57 deg. N, 2 deg. W) on several days during winter/spring 1993/94 and 1994/95. The short-timescale (~2 hours) variability observedin the columns is attributed to real atmospheric variations and is often associated with the passage of high latitude air over Aberdeen. This is confirmed by 3D modelling studies which qualitatively reproduce and rationalise the observed changes in the column data on January19 1994, January 20 1995 and February 26 1995. We describe the viewing geometry of ground-based FTIR measurements and we suggest a measurement strategy which should maximise the information retrieved on horizontal gradients in stratospheric trace species columns from FTIR measurements. [ABSTRACT FROM AUTHOR]

Abstract: We report on the consistency of water vapour line intensities in selected spectral regions between 800–12,000cm−1 under atmospheric conditions using sun-pointing Fourier transform infrared spectroscopy. Measurements were made across a number of days at both a low and high altitude field site, sampling a relatively moist and relatively dry atmosphere. Our data suggests that across most of the 800–12,000cm−1 spectral region water vapour line intensities in recent spectral line databases are generally consistent with what was observed. However, we find that HITRAN-2008 water vapour line intensities are systematically lower by up to 20% in the 8000–9200cm−1 spectral interval relative to other spectral regions. This discrepancy is essentially removed when two new linelists (UCL08, a compilation of linelists and ab-initio calculations, and one based on recent laboratory measurements by Oudot et al. (2010) in the 8000–9200cm−1 spectral region) are used. This strongly suggests that the H2O line strengths in the HITRAN-2008 database are indeed underestimated in this spectral region and in need of revision. The calculated global-mean clear-sky absorption of solar radiation is increased by about 0.3Wm−2 when using either the UCL08 or Oudot line parameters in the 8000–9200cm−1 region, instead of HITRAN-2008. We also found that the effect of isotopic fractionation of HDO is evident in the 2500–2900cm−1 region in the observations. [Copyright &y& Elsevier]

The article proposes guidelines for establishing and maintaining reference quality atmospheric observations for Reference Upper-Air Network (GRUAN) data products. It states that the precise monitoring of climate change enforces rigid requirements in observing systems particularly on the measurement accuracy and long-term stability. Moreover, the detailed theory on the calibration procedures and data processing algorithms are expected in determining the uncertainty of each individual data point.

Aims: Infection of the mouse central nervous system with wild type (WT) and vaccine strains of measles virus (MV) results in lack of clinical signs and limited antigen detection. It is considered that cell entry receptors for these viruses are not present on murine neural cells and infection is restricted at cell entry. Methods: To examine this hypothesis, virus antigen and caspase 3 expression (for apoptosis) was compared in primary mixed, neural cell cultures infected in vitro or prepared from mice infected intracerebrally with WT, vaccine or rodent neuroadapted viruses. Viral RNA levels were examined in mouse brain by nested and real-time reverse transcriptase polymerase chain reaction. Results: WT and vaccine strains were demonstrated for the first time to infect murine oligodendrocytes in addition to neurones despite a lack of the known MV cell receptors. Unexpectedly, the percentage of cells positive for viral antigen was higher for WT MV than neuroadapted virus in both in vitro and ex vivo cultures. In the latter the percentage of positive cells increased with time after mouse infection. Viral RNA (total and mRNA) was detected in brain for up to 20 days, while cultures were negative for caspase 3 in WT and vaccine virus infections. Conclusions: WT and vaccine MV strains can use an endogenous cell entry receptor(s) or alternative virus uptake mechanism in murine neural cells. However, viral replication occurs at a low level and is associated with limited apoptosis. WT MV mouse infection may provide a model for the initial stages of persistent MV human central nervous system infections. [ABSTRACT FROM AUTHOR]

Context. Research into improving feed efficiency by ruminant animals grazing pastures has historically been restrained by an inability to measure feed intake by large numbers of individual animals. Recent advances in portable breath measurement technology could be useful for this purpose but methodologies need to be developed. Aims. To evaluate predictive models for metabolisable energy intake (MEI) by free-ranging cattle using multiple short-term breath samples and then apply these to predict MEI by free-ranging cattle in a historic grazing experiment with cattle genetically divergent for residual feed intake (feed efficiency). Methods. Predictive models for MEI were developed using bodyweight (BW) data, and carbon dioxide production rate (CPR) and methane production rate (MPR) from multiple short-term breath measurements, from an experiment with long-fed Angus steers on a grain-based diet, and an experiment with short-fed Angus heifers on a roughage diet. Heat production was calculated using CPR and MPR. Energy retained (ER) in body tissue gain by steers was calculated from BW, ADG, initial and final subcutaneous fat depths, and for both groups using feeding-standards equations. Key results. Metabolic mid-test BW (MBW) explained 49 and 47% of the variation in MEI in the steer and heifer experiment, respectively, and for the steers adding ADG and then subcutaneous fat gain resulted in the models accounting for 60 and then 65% of the variation in MEI. In the steer experiment, MBWwith CPR explained 57% of the variation in MEI, and including MPR did not account for any additional variation. In the heifer experiment, MBW with CPR explained 50%, and with MPR accounted for 52% of the variation in MEI. Heat production plus ER explained 60, 35 and 85% of the variation in MEI in the steer and the heifer experiments, and in the pooled data from both experiments, respectively. Conclusions. Multiple short-term breath measurements, together simple BW data, can be used to predict MEI by free-ranging cattle in studies in which animals do not have feed-intake or ADG recorded. Implications. This methodology can be used for research into improving feed efficiency by farm animals grazing pastures. [ABSTRACT FROM AUTHOR]

Spectroscopic X-ray imaging techniques including Compton X-ray Imaging, X-ray Fluorescence Imaging and Hyperspectral X-ray Tomography require energy-resolving detectors capable of operating at high incident X-ray fluxes to make time resolved measurements. HEXITEC MHz , operates at a continuous 1 MHz frame rate and can make fully spectroscopic measurements at >106 ph s−1 mm−2. This is enabled by an integrating Front End, in-pixel digitisation and high-speed serialisers. A 300 μm thick p-type Si HEXITEC MHz detector was characterised on the B16 Test Beamline at the Diamond Light Source and are the first measurements taken at a 1 MHz frame rate. At 10 keV and 15 keV) the device displayed average FWHM of 656 eV and 682 eV respectively, with minimal changes in spectroscopic performance over ∼8 h. Analysis of charge-sharing events show low charge loss and a linear energy-signal response. Higher-flux measurements illustrated the capability of the ASIC to operate as a photon-counting device. [ABSTRACT FROM AUTHOR]

Respiration chambers are considered the reference method for quantifying the daily CH4 production rate (MPR) and CO2 production rate (CPR) of cattle; however, they are expensive, labor intensive, cannot be used in the production environment, and can be used to assess only a limited number of animals. Alternative methods are now available, including those that provide multiple short-term measures of CH4 and CO2, such as the GreenFeed Emission Monitoring (GEM) system. This study was conducted to provide information for optimizing test procedures for estimating MPR and CPR of cattle from multiple short-term CH4 and CO2 records. Data on 495 Angus steers on a 70-d ad libitum feedlot diet with 46,657 CH4 and CO2 records and on 121 Angus heifers on a 15-d ad libitum roughage diet with 7,927 CH4 and CO2 records were used. Mean (SD) age and BW were 554 d (SD 92) and 506 kg (SD 73), respectively, for the steers and 372 d (SD 28) and 348 kg (SD 37), respectively, for the heifers. The 2 data sets were analyzed separately but using the same procedures to examine the reduction in variance as more records are added and to evaluate the level of precision with 2 vs. 3 min as the minimum GEM visit duration for a valid record. The moving averages procedure as well as the repeated measures procedure were used to calculate variances for both CH4 and CO2, starting with 5 records and progressively increasing to a maximum of 80 records. For both CH4 and CO2 and in both data sets, there was a sharp reduction in the variances obtained by both procedures as more records were added. However, there was no substantial reduction in the variance after 30 records had been added. Inclusion of records with a minimum of 2-min GEM visit duration resulted in reduction in precision relative to a minimum of 3 min, as indicated by significantly (P < 0.05) more heterogeneous variances for all cases except CH4 in steers. In addition, more records were required to achieve the same level of precision relative to data with minimum GEM visit durations of 3 min. For example, in the steers, 72% reduction in initial variance was achieved with 30 records for both CH4 and CO2 when minimum GEM visit duration was 3 min, relative to 45 records when data with a minimum visit duration of 2 min were included. It is concluded from this study that when using records of multiple short-term breath measures of CH4 or CO2 for the computation of an animal's MPR or CPR, a minimum of 30 records, each record obtained from a minimum GEM visit duration of 3 min, are required. [ABSTRACT FROM AUTHOR]

Enteric methane emissions from beef cattle are a significant component of total greenhouse gas emissions from agriculture. The variation between beef cattle in methane emissions is partly genetic, whether measured as methane production, methane yield (methane production/DMI), or residual methane production (observed methane production - expected methane production), with heritabilities ranging from 0.19 to 0.29. This suggests methane emissions could be reduced by selection. Given the high cost of measuring methane production from individual beef cattle, genomic selection is the most feasible approach to achieve this reduction in emissions. We derived genomic EBV (GEBV) for methane traits from a reference set of 747 Angus animals phenotyped for methane traits and genotyped for 630,000 SNP. The accuracy of GEBV was tested in a validation set of 273 Angus animals phenotyped for the same traits. Accuracies of GEBV ranged from 0.29 ± 0.06 for methane yield and 0.35 ± 0.06 for residual methane production. Selection on GEBV using the genomic prediction equations derived here could reduce emissions for Angus cattle by roughly 5% over 10 yr. [ABSTRACT FROM AUTHOR]

The study describes significant outcomes of the ‘Metrology for Meteorology’ project, MeteoMet, which is an attempt to bridge the meteorological and metrological communities. The concept of traceability, an idea used in both fields but with a subtle difference in meaning, is at the heart of the project. For meteorology, a traceable measurement is the one that can be traced back to a particular instrument, time and location. From a metrological perspective, traceability further implies that the measurement can be traced back to a primary realization of the quantity being measured in terms of the base units of the International System of Units, the SI. These two perspectives reflect long-standing differences in culture and practice and this project – and this study – represents only the first step towards better communication between the two communities. The 3 year MeteoMet project was funded by the European Metrology Research Program (EMRP) and involved 18 European National Metrological Institutes, 3 universities and 35 collaborating stakeholders including national meteorology organizations, research institutes, universities, associations and instrument companies. The project brought a metrological perspective to several long-standing measurement problems in meteorology and climatology, varying from conventional ground-based measurements to those made in the upper atmosphere. It included development and testing of novel instrumentation as well as improved calibration procedures and facilities, instrument inter comparison under realistic conditions and best practice dissemination. Additionally, the validation of historical temperature data series with respect to measurement uncertainties and a methodology for recalculation of the values were included. [ABSTRACT FROM AUTHOR]

Ruminants contribute up to 80% of greenhouse gas (GHG) emissions from livestock, and enteric methane production by ruminants is the main source of these GHG emissions. Hence, reducing enteric methane production is essential in any GHG emissions reduction strategy in livestock. Data from 2 performance-recording research herds of Angus cattle were used to evaluate a number of methane measures that target methane production (MPR) independent of feed intake and to examine their phenotypic relationships with growth and body composition. The data comprised 777 young bulls and heifers that were fed a roughage diet (ME of 9 MJ/kg DM) at 1.2 times their maintenance energy requirements and measured for MP in open circuit respiration chambers for 48 h. Methane traits evaluated included DMI during the methane measurement period, MPR, and methane yield (MY; MPR/DMI), with means (±SD) of 6.2 ± 1.4 kg/d, 187 ± 38 L/d, and 30.4 ± 3.5 L/kg, respectively. Four forms of residual MPR (RMP), which is a measure of actual minus predicted MPR, were evaluated. For the first 3 forms, predicted MPR was calculated using published equations. For the fourth (RMPR), predicted MPR was obtained by regression of MPR on DMI. Growth traits evaluated were BW at birth, weaning (200 d of age), yearling age (400 d of age), and 600 d of age, with means (±SD) of 34 ± 4.6, 238 ± 37, 357 ± 45, and 471 ±53 kg, respectively. Body composition traits included ultrasound measures (600 d of age) of rib fat, rump fat, and eye muscle area, with means (±SD) of 3.8 ± 2.6 mm, 5.4 ± 3.8 mm, and 61 ± 7.7 cm², respectively. Methane production was positively correlated (r ± SE) with DMI (0.65 ± 0.02), MY (0.72 ± 0.02), the RMP traits (r from 0.65 to 0.79), the growth traits (r from 0.19 to 0.57), and the body composition traits (r from 0.13 to 0.29). Methane yield was, however, not correlated (r ± SE) with DMI (-0.02 ± 0.04) as well as the growth (r from -0.03 to 0.11) and body composition (r from 0.01 to 0.06) traits. All the RMP traits were strongly correlated to MY (r from 0.82 to 0.95). These results indicate that reducing MPR per se can have a negative impact on growth and body composition of cattle. Reducing MY, however, will likely have the effect of reducing MPR without impacting productivity. Where a ratio trait is undesirable, as in animal breeding, any of the RMP traits can be used instead of MY. However, where independence from DMI is desired, RMPR should be a trait worth considering. [ABSTRACT FROM AUTHOR]

A self-similar solution is derived for a radially imploding cylindrical plasma with an embedded, azimuthal magnetic field. The plasma stagnates through a strong, outward propagating shock wave of constant velocity. This analysis is an extension of the classic Noh gasdynamics problem to its ideal magnetohydrodynamics (MHD) counterpart. The present exact solution is especially suitable as a test for MHD codes designed to simulate linear Z pinches. To demonstrate the application of the new solution to code verification, simulation results from the cylindrical R-Z version of Mach2 and the 3D Cartesian code Athena are compared against the analytic solution. Alternative routines from the default ones in Athena lead to significant improvement of the results, thereby demonstrating the utility of the self-similar solution for verification. [ABSTRACT FROM AUTHOR]

It has been suggested that inflammatory processes may play a role in the development of Alzheimer’s disease (AD), and that nonsteroidal anti-inflammatory drug treatments may provide protection against the onset of AD. In the current study male Wistar rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio ratio (ALCR) schedule. When responding showed no trends, subjects were divided into groups. One group was bilaterally injected into the CA3 area of the hippocampus with 5 μl of aggregated β-amyloid (Aβ) suspension, and one group was bilaterally injected into the CA3 area of the hippocampus with 5 μl of sterile saline. Subgroups were treated twice daily with 0.1 ml (40 mg/kg) ibuprofen administered orally. The results indicated that chronic administration of ibuprofen protected against detrimental behavioural effects following aggregated Aβ injections. Withdrawal of ibuprofen treatment from aggregated Aβ-injected subjects produced a decline in behavioural performance to the level of the non-treated aggregated Aβ-injected group. Ibuprofen treatment reduced the numbers of reactive astrocytes following aggregated Aβ injection, and withdrawal of ibuprofen resulted in an increase of reactive astrocytes. These results suggest that induced inflammatory processes may play a role in AD, and that ibuprofen treatment may protect against some of the symptoms seen in AD. [Copyright &y& Elsevier]

Background: Diabetic retinopathy is associated with accumulation of advanced glycation end products in the retinal microvasculature. LR-90 is an effective multistage inhibitor of advanced glycation with renoprotective and anti-inflammatory properties. Aim: To explore the role of LR-90 in the progression of experimental diabetic retinopathy. Methods: Streptozotocin-induced diabetic Sprague-Dawley rats were treated with LR-90 (50 mg/I in drinking water) for up to 32 weeks. At the end of the study, eyes were enucleated and subjected to trypsin digestion and staining with light green/haematoxylin. Acellular capillaries and pericytes were quantified in random fields using light microscopy. Results: In the LR-90-treated diabetic animals, acellular capillary numbers were reduced to 1.63(0.20) from 2.58 (0.49) (p<0.05) in diabetic controls. LR-90 treatment also restored the pericyte deficit from 18.12 (0.98) in diabetic rats to 24.19 (0.76) (p<0.001). Conclusion: These findings show that LR-90 can effectively inhibit important lesions of diabetic retinopathy. This agent has potential for preventing retinopathy in patients with diabetes. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Retinal vascular calibre changes may reflect early subclinical microvascular disease in diabetes. Because of the considerable homology between retinal and cerebral microcirculation, we examined whether retinal vascular calibre, as a proxy of cerebral microvascular disease, was associated with cognitive function in older people with type 2 diabetes., Methods: A cross-sectional analysis of 954 people aged 60-75 years with type 2 diabetes from the population-based Edinburgh Type 2 Diabetes Study was performed. Participants underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Retinal vascular calibre was measured from an image field with the optic disc in the centre using a validated computer-based program., Results: After age and sex adjustment, larger retinal arteriolar and venular calibres were significantly associated with lower scores for the Wechsler Logical Memory test, with standardised regression coefficients -0.119 and -0.084, respectively (p < 0.01), but not with other cognitive tests. There was a significant interaction between sex and retinal vascular calibre for logical memory. In male participants, the association of increased retinal arteriolar calibre with logical memory persisted (p < 0.05) when further adjusted for vocabulary, venular calibre, depression, cardiovascular risk factors and macrovascular disease. In female participants, this association was weaker and not significant., Conclusions/interpretation: Retinal arteriolar dilatation was associated with poorer memory, independent of estimated prior cognitive ability in older men with type 2 diabetes. The sex interaction with stronger findings in men requires confirmation. Nevertheless, these data suggest that impaired cerebral arteriolar autoregulation in smooth muscle cells, leading to arteriolar dilatation, may be a possible pathogenic mechanism in verbal declarative memory decrements in people with diabetes.

Retinopathy is a major complication of diabetes mellitus and this condition remains a leading cause of blindness in the working population of developed countries. As diabetic retinopathy progresses a range of neuroglial and microvascular abnormalities develop although it remains unclear how these pathologies relate to each other and their net contribution to retinal damage. From a haemodynamic perspective, evidence suggests that there is an early reduction in retinal perfusion before the onset of diabetic retinopathy followed by a gradual increase in blood flow as the complication progresses. The functional reduction in retinal blood flow observed during early diabetic retinopathy may be additive or synergistic to pro-inflammatory changes, leucostasis and vaso-occlusion and thus be intimately linked to the progressive ischaemic hypoxia and increased blood flow associated with later stages of the disease. In the current review a unifying framework is presented that explains how arteriolar dysfunction and haemodynamic changes may contribute to late stage microvascular pathology and vision loss in human diabetic retinopathy.

Aims/hypothesis: Recent studies suggest that oxidative stress should be monitored alongside HbA(1c) to identify subgroups of diabetic patients at high risk of initiation or progression of retinopathy. The acrolein-derived advanced lipoxidation end-product (ALE), [Formula: see text]-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine), is a useful biomarker that reflects the cumulative burden of oxidative stress over long periods of time. The purpose of the present study was to investigate whether serum and haemoglobin levels of FDP-lysine are associated with the severity of diabetic retinopathy in type 1 and type 2 diabetic patients., Methods: Serum and haemoglobin levels of FDP-lysine were measured by competitive ELISA in 59 type 1 and 76 type 2 diabetic patients with no retinopathy, non-proliferative retinopathy or proliferative retinopathy (mean age [+/-SEM] 54.3 +/- 1.3 years), and in 47 non-diabetic control individuals (mean age 51.9 +/- 2.1 years)., Results: Serum and haemoglobin levels of FDP-lysine were significantly increased in diabetic patients compared with control individuals (p = 0.04 and p = 0.002, respectively). However, no significant association was found between levels of serum FDP-lysine and the severity of diabetic retinopathy (p = 0.97). In contrast, increased haemoglobin FDP-lysine levels were observed in patients with proliferative retinopathy compared with patients without retinopathy and with non-proliferative retinopathy (p = 0.04). The relationship of FDP-lysine with proliferative retinopathy was unaltered after adjustment for HbA(1c), or other clinical parameters., Conclusions/interpretation: Our data suggest that haemoglobin FDP-lysine may provide a useful risk marker for the development of proliferative diabetic retinopathy independently of HbA(1c), and that elevated intracellular ALE formation may be involved in the pathogenesis of this sight-threatening complication of diabetes.

Purpose: Hypoxia driven ocular angiogenesis occurs in a range of ischemic retinopathies including proliferative diabetic retinopathy and retinopathy of prematurity. These conditions are initiated and sustained by hypoxia dependent vascular endothelial growth factor (VEGF) expression in the eye. There are two families of VEGF isoforms formed by differential splicing, the pro-angiogenic VEGF family, known to contribute to ocular neovascularization, and the anti-angiogenic VEGF family, which are downregulated in diabetic retinopathy in humans. The first member of the VEGF family to be isolated was VEGF165b. To determine whether VEGF165b could inhibit hypoxia driven angiogenesis in the eye, the oxygen induced retinopathy mouse model of ocular neovascularization was used., Methods: 1 ng of recombinant human VEGF165b peptide was injected intraocularly upon return to normoxia after 5 days exposure to 95% oxygen, and neovascularization assessed., Results: VEGF165b significantly inhibited the percentage area of retinal neovascularization from 23+/-3% to 12+/-3.3%, and significantly increased normal vascular areas from 62+/-4% to 74+/-4%. The percentage area of residual ischemic retina was not affected., Conclusions: These results show that a single injection of VEGF165b can significantly reduce preretinal neovascularization without inhibition of physiological intraretinal angiogenesis. Controlling the balance of VEGF(xxx) to VEGF(xxx) isoforms may therefore be therapeutically valuable in the treatment of proliferative eye diseases such as diabetic retinopathy and age related macular degeneration. The regulation of splicing between these two families of isoforms may provide a novel therapeutic strategy for proliferative eye disease.