bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of sleep deprivation on wound healing
Authors: MOSTAGHIMI L. , OBERMEYER W. H. , BALLAMUDI B. , MARTINEZ–GONZALEZ D. , BENCA R. M.
Published: August 2005

Sleep deprivation is widely regarded as a stressor and has been shown to have significant effects on host defences. Severely sleep‐deprived rats develop lesions on their paws and tails, suggesting possible deficits in the healing process. The purpose of this study was to assess the impact of rapid eye‐movement (REM) sleep deprivation (RSD) on wound healing in a rat model. Male dark‐hooded Long‐Evans rats, 2–4 months old, were subjected to dorsal application of two sterile punch biopsies, each 3.5 mm in size. Biopsies were performed either immediately before or immediately after 5 days of sleep deprivation. Wound healing in REM sleep‐deprived animals was compared with home cage control and yoked control animals. RSD did not produce differences in the rate of healing, regardless of the timing of the biopsy punch. RSD does not appear to have significant effects on wound healing and thus appears to act differently from other types of stressors on wound healing.
Effects of playing a computer game using a bright display on presleep physiological variables, sleep latency, slow wave sleep and REM sleep
Authors: HIGUCHI SHIGEKAZU , MOTOHASHI YUTAKA , LIU YANG , MAEDA AKIRA
Published: August 2005

Epidemiological studies have shown that playing a computer game at night delays bedtime and shortens sleeping hours, but the effects on sleep architecture and quality have remained unclear. In the present study, the effects of playing a computer game and using a bright display on nocturnal sleep were examined in a laboratory. Seven male adults (24.7 ± 5.6 years old) played exciting computer games with a bright display (game‐BD) and a dark display (game‐DD) and performed simple tasks with low mental load as a control condition in front of a BD (control‐BD) and DD (control‐DD) between 23:00 and 1:45 hours in randomized order and then went to bed at 2:00 hours and slept until 8:00 hours. Rectal temperature, electroencephalogram (EEG), heart rate and subjective sleepiness were recorded before sleep and a polysomnogram was recorded during sleep. Heart rate was significantly higher after playing games than after the control conditions, and it was also significantly higher after using the BD than after using the DD. Subjective sleepiness and relative theta power of EEG were significantly lower after playing games than after the control conditions. Sleep latency was significantly longer after playing games than after the control conditions. REM sleep was significantly shorter after the playing games than after the control conditions. No significant effects of either computer games or BD were found on slow‐wave sleep. These results suggest that playing an exciting computer game affects sleep latency and REM sleep but that a bright display does not affect sleep variables.
The dim light melatonin onset following fixed and free sleep schedules
Authors: BURGESS HELEN J. , EASTMAN CHARMANE I.
Published: August 2005

The time at which the dim light melatonin onset (DLMO) occurs can be used to ensure the correct timing of light and/or melatonin administration in order to produce desired circadian phase shifts. Sometimes however, measuring the DLMO is not feasible. Here we determined if the DLMO was best estimated from fixed sleep times (based on habitual sleep times) or free (ad libitum) sleep times. Young healthy sleepers on fixed (n = 60) or free (n = 60) sleep schedules slept at home for 6 days. Sleep times were recorded with sleep logs verified with wrist actigraphy. Half‐hourly saliva samples were then collected during a dim light phase assessment and were later assayed to determine the DLMO. We found that the DLMO was more highly correlated with sleep times in the free sleepers than in the fixed sleepers (DLMO versus wake time, r = 0.70 and r = 0.44, both P < 0.05). The regression equation between wake time and the DLMO in the free sleepers predicted the DLMO in an independent sample of free sleepers (n = 23) to within 1.5 h of the actual DLMO in 96% of cases. These results indicate that the DLMO can be readily estimated in people whose sleep times are minimally affected by work, class and family commitments. Further work is necessary to determine if the DLMO can be accurately estimated in people with greater work and family responsibilities that affect their sleep times, perhaps by using weekend wake times, and if this method will apply to the elderly and patients with circadian rhythm disorders.
A single‐nucleotide polymorphism in the 5′‐untranslated region of the hPER2 gene is associated with diurnal preference
Authors: CARPEN JAYSHAN D. , ARCHER SIMON N. , SKENE DEBRA J. , SMITS MARCEL , VON SCHANTZ MALCOLM
Published: August 2005

The PERIOD2 (PER2) gene is a key component of the molecular mechanism that generates circadian rhythms in mammals. A missense mutation in the human PER2 gene has previously been linked to advanced sleep phase syndrome (ASPS). We have investigated three other single‐nucleotide polymorphisms in the hPER2 gene, one downstream of the transcription start site (C−1228T), one in exon 2 in the 5′‐untranslated region (5′‐UTR) (C111G), and one missense mutation (G3853A) causing a glycine to glutamine substitution in the predicted protein. Subjects selected from a group of 484 volunteers for extreme morning or evening preference, or intermediate diurnal preference were genotyped with regard to the three polymorphisms (n = 35 for each group). Whereas allele frequencies for the other two polymorphisms did not differ significantly between any of the groups, the 111G allele frequency was significantly higher in subjects with extreme morning preference (0.14) than in subjects with extreme evening preference (0.03) (Fisher's exact test, two‐sided P value = 0.031, odds ratio = 5.67). No significant difference in 111G allele frequency was observed between either of these groups and subjects with intermediate diurnal preference. Computer prediction indicated that the C111G polymorphism, which occurs 12 bases upstream from the translation start codon, might alter the secondary structure of the transcript. The PER2 111G allele associates with morning preference and is a potential candidate allele for ASPS.
In situ hatching of invertebrate diapausing eggs from ships’ ballast sediment
Authors: Bailey Sarah A. , Nandakumar Kanavillil , Duggan Ian C. , Van Overdijk Colin D. A. , Johengen Thomas H. , Reid David F. , MacIsaac Hugh J.
Published: August 2005

Ships that enter the Great Lakes laden with cargo carry only residual ballast water and sediment in ballast tanks. These ships are designated ‘no ballast on board’ (NOBOB) and constitute > 90% of inbound traffic. We conducted in situ experiments using emergence traps to assess the viability and the introduction potential of invertebrate diapausing stages present in ships’ ballast sediment. All trials commenced while vessels operated on the lower lakes (Erie, Ontario) and were completed 6–11 days later at ports on the upper lakes (Michigan, Lake Superior). Eight trials were conducted on four ships using five different ballast sediments. Hatching was observed on every ship, although not from all sediments on all ships. Overall hatch rates were very low (0.5 individuals per 500 g sediment), typically involving activation of < 0.05% of total eggs present. Five species of rotifers and copepod nauplii were hatched from ballast sediments, although only one or two species typically hatched from any one sediment. Results of this study indicate that hatching of diapausing eggs contained in ballast sediment of NOBOB ships poses a relatively low risk of invasion to the Great Lakes. However, as reproduction may occur in tanks, and non‐indigenous species may be involved in numerous introduction events, the risk posed by this vector is small but potentially important. While dormancy is a characteristic enabling enhanced survival during transportation in ballast tanks, it becomes a hindrance for introduction.
Comparative taxonomic structure of the floras of two Mediterranean‐climate regions: Iberia and California
Authors: Lozano Felipe Domínguez , Schwartz Mark W.
Published: August 2005

Two major events were invoked to understand recent biodiversity patterns in Mediterranean floras: northern hemisphere glaciations and historical human impacts. These two events were considered in this work, where we investigated general patterns in plant species richness and rarity attributes in two different Mediterranean regions: California and Iberia. Our goal was to assess whether comparisons of this sort provided evidence of different extinctions rates, making an effort to decouple anthropogenic from ice age‐related effects in both regions.

We employed a taxonomically revised database for eight Mediterranean floras containing information on species richness for 298 families and rarity attributes for 11,834 taxa. We used summary statistics (Gini coefficient) and randomly generated models to test for general patterns of the distribution of diversity within and among taxonomic groups. We then used this general pattern among Mediterranean floras to provide a context in which to evaluate our two focal areas.

Results indicated that floras of California and Iberia share the closest taxonomic structure among Mediterranean regions. Differences emerged in rarity attributes and the taxonomic identities of rarity rich groups. These findings were interpreted in the light of Pleistocene changes. In addition, a closer focus on rarity attributes allowed us to pinpoint some segments of these floras where anthropogenic activities may drive variation from general patterns, specifically for rare species in ecologically sensitive habitats.
Does the recruitment of a non‐native mussel in native eelgrass habitat explain their disjunct adult distributions?
Authors: Williams S. L. , Ebert T. A. , Allen B. J.
Published: August 2005

We studied variability in the abundance of small individuals of an invasive mussel (Musculista senhousia) across the depth distribution of a native marine angiosperm, eelgrass (Zostera marina). Adult mussels and eelgrass have a disjunct local distribution, each limiting the other in complex ways. To assess whether eelgrass also influenced the distribution of juvenile mussels, we sampled inside and outside eelgrass beds in one site in Mission Bay and two in San Diego Bay, California, USA. We sampled mussels in size classes 0.26–0.50 mm, 0.51–1.00 mm, 1.10–2.00 mm and > 2.00 mm from September 1997 to April 1999. We also monitored gonad development in larger mussels and in situ growth of mussels ≤ 2 mm tagged with the chemical marker calcein. Spatial and temporal variations in mussel abundances were high but seasonal patterns were roughly similar at San Diego Bay sites; very few mussels were found in Mission Bay. Mussels with full gonads were found year‐round in San Diego Bay, as were mussels in the smallest size class (with a large peak in fall and a smaller secondary one in spring), suggesting that many of the smallest mussels represent recruitment. The observation that most, although not all, tagged mussels increased in size provides further support for recruitment. Some of the highest numbers of mussels in the smallest size class were found inside eelgrass beds, indicating that eelgrass does not restrict and may actually enhance the distribution of very small mussels. The disjunct distribution of adult mussels and eelgrass thus is apparently established primarily postrecruitment. M. senhousia is capable of year‐round reproduction, recruitment and growth, and thus is poised to preempt space from eelgrass following any disturbance that results in eelgrass declines, such as habitat fragmentation, eutrophication, or disease.
Potential consequences of the coqui frog invasion in Hawaii
Authors: Beard Karen H. , Pitt William C.
Published: August 2005

The Puerto Rican frog, Eleutherodactylus coqui, has invaded Hawaii and has negatively impacted the state's multimillion dollar floriculture, nursery and tourist industries; however, little is known about the ecological consequences of the invasion. Using data from Puerto Rico and Hawaii, the authors summarize the potential consequences of the invasion and describe future research needs. It could be predicted that the coqui would reduce the abundance of Hawaii's endemic invertebrates. However, data suggest that coquis are mostly consuming non‐native invertebrates, and not invertebrate pests, such as mosquitoes and termites. Endemic invertebrates are likely to represent a portion of the coqui diet, but it remains uncertain which endemic invertebrates are most threatened by coqui predation and whether there will be indirect effects that benefit or harm them. It could be predicted that coquis would compete with endemic birds for invertebrate prey, but there is presently little overlap in the habitats used by coquis and endemic birds. Although, coquis may make bird re‐invasion into lowland ecosystems more difficult; alternatively, coquis could serve as an additional food source for some endemic birds. Finally, it could be predicted that coquis serve as a food source for endemic‐bird predators, such as rats and mongoose, and bolster their abundance. Preliminary data suggest that coquis will not bolster rat or mongoose populations. Managing coqui populations in Hawaii has been a challenge. A population has not yet been eradicated using citric acid, the only federally approved pesticide for coquis. It is unlikely that coquis will ever be eradicated from the islands of Hawaii and Maui, where there are now hundreds of populations. Quick and severe responses to new introductions may be the only effective means of containing the spread of the coqui.
Evaluation of weed eradication programs: the delimitation of extent
Authors: Panetta F. Dane , Lawes Roger
Published: August 2005

Eradication is a management strategy that can provide substantial ecological and economic benefits by eliminating incursions of pest organisms. In contrast to eradication efforts that target other pests, weed eradication programs can be very protracted owing to the presence of persistent seed banks and difficulties in detecting the target. Hence there is a need to develop criteria to assist in the evaluation of progress towards eradication. Knowledge of the extent of a weed incursion (the ‘delimitation’ criterion) is considered fundamental for eradication success, as an incursion will progress from any infestations that remain undetected and thus uncontrolled. This criterion is examined with regard to eradication programs targeting Bassia scoparia L. A.J. Scott [= Kochia scoparia L. Schrader], Chondrilla juncea L. (both in Western Australia) and Orobanche ramosa L. in South Australia. The B. scoparia incursion, which has been eradicated, was largely delimited within 12 months of the inception of its eradication program. In contrast, the Western Australian C. juncea incursion has never been delimited, owing to insufficient investment in surveillance during an eradication program spanning 30 years. An exponential decrease in the detection ratio (infested area detected/area searched) over time suggests that delimitation has been approached within 6 years of the inception of the eradication program for O. ramosa. An effective surveillance program is essential for achieving delimitation of a weed incursion.
The diversity and distribution of lianas in the Afromontane rain forests of Ethiopia
Authors: Senbeta Feyera , Schmitt Christine , Denich Manfred , Demissew Sebsebe , Velk Paul L. G. , Preisinger Helmut , Woldemariam Tadesse , Teketay Demel
Published: August 2005

The diversity and distribution of lianas were studied in five Afromontane rain forests of Ethiopia. Quadrats of 20 × 20 m were laid down along transects in the Bonga, Berhane‐Kontir, Harenna, Yayu and Maji forests. In all forests, 30,917 liana individuals belonging to 123 species in 87 genera and 40 plant families were recorded. The most species‐rich families were Asclepiadaceae (14), Fabaceae (9), Annonaceae (7) and Cucurbitaceae (7). The top 10 dominant families represented 56% of the total number of species. Over 400 other plant species representing different life forms were recorded growing together with lianas. The lianas accounted for over 30% of the total woody plant diversity and over 20% of the total floral diversity in the study areas. The analysis of floristic composition of the forests indicates that the Berhane‐Kontir Forest had the highest Fisher's diversity index α, and Yayu the lowest. Generally, there were low similarities between the forests in terms of species composition. Although lianas were abundant in almost all forests, there was a considerable variation among the forests in terms of density and spatial distribution. The major dispersal modes of lianas were anemochory (30%), mammaliochory (30%), ornithochory and autochory, and the four mechanisms of climbing of lianas were twining (54%), hooking (24%), rooting and use of tendrils. Altitude and human disturbance were found to be important factors affecting liana distribution. The need for sustainable management and use of lianas in the Afromontane rain forests is emphasized.
A diffusion approach to the electrolyte leakage  from plant tissues
Authors: Kocheva Konstantina V. , Georgiev Georgi Iv. , Kochev Valery K.
Published: August 2005

The exchange of ions between plant tissues and the external solution in vitro exhibits prominent biphasic kinetics. This is generally ascribed to the different contribution of the two compartments – apoplast and symplast – involved in the process. In this regard, an electro‐diffusion model of the leakage is proposed in the paper. On the basis of the balance of fluxes through the plasmalemma and the cell wall, a system of differential equations describing the ion concentration in the outer solution is found. For a wide range of the system's coefficients, its behaviour is well approximated by a previously obtained analytical function. The values of the function's parameters, derived from the fit with experimental data, correlate adequately with the water deficit conditions of the samples. Hence, these parameters may be used to characterize the physiological status of the investigated plants.
Elevated CO2 and limited nitrogen nutrition can restrict excitation energy dissipation in photosystem II of Japanese white birch (Betula platyphylla var. japonica) leaves
Authors: Kitao Mitsutoshi , Koike Takayoshi , Tobita Hiroyuki , Maruyama Yutaka
Published: August 2005

Elevated atmospheric CO2 concentration [CO2] and different levels of nitrogen (N) nutrition can influence the amount of excess excitation energy in photosystem (PS) II and related photosynthetic properties. The interactive effect of two [CO2] levels (ambient: 360 µM M−1 and elevated: 720 µM M−1) and two N levels (high: 700 mg N plant−1 and low: 100 mg N plant−1) on these properties was examined in seedlings of Japanese white birch (Betula platyphylla var. japonica) using simultaneous measurements of gas exchange and chlorophyll fluorescence. Photosynthetic acclimation to elevated [CO2], as indicated by a decline in carboxylation efficiency (CE), was observed in plants grown at elevated [CO2] especially under low N. Elevated [CO2] resulted in a decrease in area‐based leaf N content (Narea) irrespective of N treatment. The adverse effect of elevated [CO2] and low N on CE may have been exacerbated by a greater accumulation of leaf sugar and starch contents in these plants leading to a lower electron transport rate (ETR). While these plants also showed higher non‐photochemical quenching (NqP) that could offset the reduction in energy dissipation through ETR to some extent, they still have a higher risk of photoinhibition from excessive excitation energy in PSII as indicated by a decrease in photochemical quenching (qP). However, chronic photoinhibition was not observed in plant grown at elevated [CO2] and low N because they showed no difference in Fv/Fm (the maximum photochemical efficiency of PSII) from those grown at ambient [CO2] and low N after an overnight dark adaptation. High levels of NqP in plants grown at elevated [CO2] and low N reflect a near saturation of thermal energy dissipation. This impaired capacity of photoprotection would render these plants more vulnerable to photoinhibition in the event of additional environmental stresses such as drought, low or high temperature.
Expression and activity of type 1 NAD(P)H dehydrogenase at different growth phases of the cyanobacterium, Synechocystis PCC 6803
Authors: Ma Weimin , Mi Hualing
Published: August 2005

The expression and activity of type 1 NAD(P)H dehydrogenase (NDH‐1) were investigated in Synechocystis PCC 6803 cells during different growth phases (i.e. lag, logarithmic, stationary and decline phases). The relative amount of NDH‐1, estimated by Western blot analysis using antibodies against NdhH, NdhI and NdhK, increased more than two‐fold during growth from the lag to the logarithmic phase and then decreased after the logarithmic phase to reach lowest levels after 15 days (decline phase). The activity of light‐dependent NADPH oxidation and cyclic electron flow around photosystem I (PSI) changed nearly in parallel with the amount of NdhH, NdhI and NdhK in cells across the growth phases. In contrast, the activity of photosynthetic O2 evolution and respiratory O2 uptake was not significantly different across phases of growth; the fluctuation of the activity at different phases was within 40%. These results suggested that the activity of light‐dependent NADPH oxidation and PSI‐cyclic electron flow are restricted by the amount of NDH‐1 and that other factor(s) are limiting the rates of photosynthesis and respiration.
Glycaemic control in relation to xanthine oxidase and antioxidant indices in Malaysian Type 2 diabetes patients
Authors: Kuppusamy U. R. , Indran M. , Rokiah P.
Published: August 2005

Aims  Increased oxidative stress and oxidative damage are present in Type 2 diabetes mellitus (DM). The aim of this study was to assess the oxidative stress levels in the three major ethnic groups in Malaysia and to study the association between glycaemic control and oxidant–antioxidant levels in these patients.

Methods  Oxidative indices and glycaemic control were assessed in 650 Type 2 DM patients and 280 healthy age‐matched controls by known established methods.

Results  Type 2 DM patients had significantly lower levels of antioxidant enzymes and non‐enzymatic antioxidant (FRAP) and increased levels of HbA1c, fasting blood glucose (FBG), malondialdehyde (MDA) and xanthine oxidase (XO) when compared with control subjects. Markers of oxidative stress were more apparent in Indian patients compared with Malay and Chinese patients. Correlation analysis of oxidant–antioxidant parameters as a function of HbA1c in each ethnic group revealed a strong association of HbA1c with oxidative indices.

Conclusions  The present study provides evidence for the possible contribution of XO to oxidative stress and the pathophysiology of diabetes. HbA1c remains an important marker of glycaemic control for the management of Type 2 DM, but other confounding factors that predispose or lead to oxidative stress should also be taken into consideration.
The association of aldose reductase gene (AKR1B1) polymorphisms with diabetic neuropathy in adolescents
Authors: Donaghue K. C. , Margan S. H. , Chan A. K. F. , Holloway B. , Silink M. , Rangel T. , Bennetts B.
Published: August 2005

Aims  Variants in the aldose reductase gene (AKR1B1) have been implicated in the development of diabetic retinopathy and nephropathy, with the most convincing data identifying a (CA)n repeat microsatellite allele (Z−2), which has a functional role in gene expression. In this study the association between polymorphisms in the AKR1B1 gene and diabetic neuropathy was investigated.

Methods  The pupillary response to light was used as the major outcome in this study along with abnormal hot thermal threshold. Three hundred and sixty‐three adolescents underwent genotyping of the AKR1B1 gene. The microsatellite (CA)n repeat was sequenced and two single nucleotide polymorphisms, −106C→T and −12C→G, were investigated by restriction fragment length polymorphism.

Results  Seventy‐six percent of participants had pupillary abnormalities (45% with two, 15% with three abnormalities). Presence of the Z−2/Z−2 genotype increased the risk nearly three‐fold for pupillary abnormalities [odds ratio (OR) 3.02, 95% confidence interval (CI) 1.14, 7.98). The susceptibility genotypes (Z−2/Z−2 with −106C/−106C, Z−2/Z with −106C/−106C or Z/Z with −106C/−106C) were associated with resting pupil diameter abnormalities when compared with the protective genotypes (Z+2/Z+2 or −106T/−106T) (OR 2.83, 95% CI 1.25, 6.41). The combination of Z+2/−106T reduced the risk of abnormal heat discrimination (OR 0.48, 95% CI 0.23, 0.99).

Conclusions  In this study we have shown that Z−2/Z−2 genotype is significantly associated with the development of pupillary abnormality, an early indicator of diabetic autonomic neuropathy, in adolescent Australian patients with Type 1 diabetes.
Inter‐relationships between DNA damage, ascorbic acid and glycaemic control in Type 2 diabetes mellitus
Authors: Choi S. W. , Benzie I. F. F. , Lam C. S. Y. , Chat S. W. S. , Lam J. , Yiu C. H. , Kwan J. J. , Tang Y. H. , Yeung G. S. P. , Yeung V. T. F. , Woo G. C. , Hannigan B. M. , Strain J. J.
Published: August 2005

Aims  The onset of complications in Type 2 diabetes mellitus (DM) patients cannot be predicted in individuals. Evidence suggests a link between complications and hyperglycaemia, oxidative stress and antioxidants, but causality is unclear. This study investigated baseline (entry) fasting plasma ascorbic acid, lymphocytic DNA damage and glycaemic control in Type 2 DM as part of a long‐term study, the aim of which is to explore a biomarker profiling approach to identify and improve outcome in high‐risk subjects.

Methods  A cross‐sectional study, in which DNA damage, glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and ascorbic acid (AA) were measured on fasting blood samples collected from 427 Type 2 DM subjects.

Results  DNA damage was significantly (P < 0.0001) and directly correlated to both FPG (r = 0.540) and HbA1c (r = 0.282), and was significantly (P < 0.0001), independently and inversely correlated to plasma AA (r = −0.449). In those subjects with both poor glycaemic control and low AA (< 48 µm, the overall mean value for the study group), DNA damage was significantly (P < 0.005) higher compared with those subjects with a similar degree of hyperglycaemia but with AA above the mean.

Conclusions  The novel finding of a significant inverse relationship between plasma AA and DNA damage in Type 2 DM indicates that poorly controlled diabetic subjects might benefit from increased dietary vitamin C. The data also have important implications for biomarker profiling to identify those subjects who might benefit most from intensive therapy. Longer‐term follow‐up is underway.
The gap between guidelines and reality: Type 2 diabetes in a national diabetes register 1996–2003
Authors: Eliasson B. , Cederholm J. , Nilsson P. , Gudbjörnsdóttir S. ,   for the Steering Committee of the Swedish National Diabetes Register
Published: August 2005

Guidelines for the treatment of risk factors in diabetes care have been updated recently, due to indisputable results from clinical end‐point trials. This study evaluates risk factor control compared with current national and international targets during the period 1996–2003 in Type 2 diabetes (DM2). Patients were registered in primary‐care and hospital outpatient clinics using computer software, or via the Internet. The clinical characteristics of the patients, treatment, HbA1c, and risk factors were reported after screening by local methods. The numbers of cases of DM2 reported were 17547 in 1996 and 57119 in 2003. The mean HbA1c decreased from 7.8 to 7.2%, while blood pressure decreased from 150/82 to 143/78 mmHg during the same period. Longitudinal analysis of results was performed in 5356 patients repeatedly reported, showing slightly lower effects. The new European treatment targets of HbA1c≤ 6.1%, blood pressure < 130/80 mmHg and total cholesterol < 4.5 mmol/l were attained by 16, 13 and 28% of the patients in 2003, respectively. The prevalence of the metabolic syndrome in 2003 was 77%. Aspirin was prescribed in 36% of cases. Lipid‐lowering, anti‐hypertensive drugs, and treatment with oral hypoglycaemic agents in combination with insulin were increasingly employed during the period studied. Risk factor control in DM2 reported to the National Diabetes Register (NDR) is slowly improving, although multiple risk factors and the metabolic syndrome are found in most patients. The majority of subjects do not achieve current target levels for HbA1c, blood pressure and blood lipids. Thus, giving up smoking and increased use of aspirin are called for, as well as more aggressive treatment of hyperglycaemia, elevated blood pressure and blood lipid levels, in accordance with updated international guidelines.
Heavy alcohol intake, homocysteine and Type 2 diabetes
Authors: Sakuta H. , Suzuki T. , Katayama Y. , Yasuda H. , Ito T.
Published: August 2005

Although moderate alcohol intake is associated with reduced risk of atherosclerotic disease in both the general population and in diabetic patients, a recent report suggests that heavy alcohol intake facilitates the development of atherosclerosis exclusively in diabetic individuals. We studied cross‐sectionally the effects of the interaction between ethanol consumption category and the prevalence of diabetes on plasma total homocysteine (tHcy), a risk factor for atherosclerotic disease, in middle‐aged men. Heavy drinking was associated with elevated tHcy levels only in diabetic subjects but not in non‐diabetic subjects. Plasma tHcy of heavy drinkers (average ethanol consumption > 30 ml/day) was higher than that of abstainers in the diabetic subgroup (10.25 ± 3.39 vs. 8.88 ± 1.94 µmol/l, P < 0.05), whereas tHcy levels in heavy drinkers were comparable with that of abstainers in the non‐diabetic subgroup (9.36 ± 2.52 vs. 9.12 ± 2.10 µmol/l, NS). In a two‐factor anova, significant interaction was observed on the effects of ethanol consumption category and diabetes prevalence on tHcy levels (P < 0.01). Confounding factors including folate, vitamin B12, creatinine, age or cigarette smoking did not contribute to the interaction. These findings may partly explain the reported association between heavy drinking and atherosclerosis in diabetic subjects.
Are insulin resistance, impaired fasting glucose and impaired glucose tolerance all equally strongly related to age?
Authors:   The DECODE Study Group
Published: August 2005

Background  Insulin resistance (IR) has been considered an underlying cause of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Whether IR increases with age has been debated. We investigated the age‐associated deterioration in the homeostasis model assessment (HOMA) of IR and in glucose metabolism.

Methods  Ten (nine including women) European studies contributed data on 6314 men and 6393 women aged 30–88 years. The cohort‐ and sex‐specific top 25% of HOMA of IR in non‐diabetic subjects was used to define HOMA‐IR.

Results  Compared with subjects aged 50–59 years, the cohort‐ and body mass index‐adjusted odds ratio (95% confidence interval) for HOMA‐IR was 0.83 (0.64, 1.08), 0.87 (0.74, 1.03), 1.20 (1.02, 1.42) and 1.45 (1.10, 1.92) in men and 0.84 (0.62, 1.14), 0.91 (0.77, 1.09), 1.38 (1.19, 1.62) and 1.71 (1.35, 2.17) in women, respectively, aged 30–39, 40–49, 60–69 and ≥ 70 years (P < 0.0001 for trend test). The same increasing trend was also observed for IFG. In contrast, the corresponding odds ratios for IGT increased linearly and more strongly with age, being 0.37 (0.22, 0.63), 0.67 (0.52, 0.87), 1.55 (1.24, 1.92) and 2.96 (2.13, 4.13) in men and 0.51 (0.31, 0.85), 0.66 (0.52, 0.86), 1.92 (1.57, 2.35) and 3.85 (2.89, 5.12) in women, respectively.

Conclusions  Age is more strongly associated with IGT than with HOMA‐IR or IFG in non‐diabetic European populations.
Continuous glucose monitoring and closed‐loop systems
Authors: Hovorka R.
Published: August 2005

Background The last two decades have witnessed unprecedented technological progress in the development of continuous glucose sensors, resulting in the first generation of commercial glucose monitors. This has fuelled the development of prototypes of a closed‐loop system based on the combination of a continuous monitor, a control algorithm, and an insulin pump.

Method A review of electromechanical closed‐loop approaches is presented. This is followed by a review of existing prototypes and associated glucose sensors. A literature review was undertaken from 1960 to 2004.

Results Two main approaches exist. The extracorporeal s.c.–s.c. approach employs subcutaneous glucose monitoring and subcutaneous insulin delivery. The implantable i.v.–i.p. approach adopts intravenous sampling and intraperitoneal insulin delivery. Feasibility of both solutions has been demonstrated in small‐scale laboratory studies using either the classical proportional–integral–derivative controller or a model predictive controller. Performance in the home setting has yet to be demonstrated.

Conclusions The glucose monitor remains the main limiting factor in the development of a commercially viable closed‐loop system, as presently available monitors fail to demonstrate satisfactory characteristics in terms of reliability and/or accuracy. Regulatory issues are the second limiting factor. Closed‐loop systems are likely to be used first by health‐care professionals in controlled environments such as intensive care units.
Oxidized‐LDL levels are changed during short‐term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria
Authors: Paniagua J. A. , López‐Miranda J. , Pérez‐Martínez P. , Marín C. , Vida J. M. , Fuentes F. , Fernández de la Puebla R. A. , Pérez‐Jiménez F.
Published: August 2005

Aims  To investigate the role of HMG‐CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox‐LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers.

Methods  In a double‐blind, randomized crossover study, 15 obese diet‐treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox‐LDL levels were measured fasting and during a euglycaemic–hyperinsulinaemic clamp (∼5.5 mmol/l; EHC) and a hyperglycemic clamp (∼20 mmol/l; HC). An endothelium‐dependent flow‐mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S‐ICAM, s‐VCAM and basal prothrombotic factors were also measured.

Results  During cerivastatin treatment, basal circulating ox‐LDL levels decreased by 48% (P < 0.001) compared with placebo. Serum ox‐LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P < 0.001) and the increments in FMD correlated with decrements in serum ox‐LDL levels (r = 0.78, P = 0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P < 0.05). Basal sICAM‐1 and sVCAM‐1 levels decreased (P < 0.01 and P < 0.05, respectively).

Conclusions  In early obese Type 2 diabetic patients, serum ox‐LDL levels are influenced by short‐term serum glucose variations and lowered with cerivastatin therapy. During cerivastatin treatment, improved flow‐mediated endothelium‐dependent dilation was associated with decrements in circulating ox‐LDL levels and the hyperinsulinaemia‐induced urinary albumin excretion was blunted.
Clinically apparent atherosclerotic disease in diabetes is associated with an increase in platelet microparticle levels
Authors: Tan K. T. , Tayebjee M. H. , Lim H. S. , Lip G. Y. H.
Published: August 2005

Background  The commonest cause of mortality in patients with Type 2 diabetes is atherothrombosis, which can be related to abnormalities in the coagulation and fibrinolytic pathways, as well as in platelet function. Platelet microparticles (PMPs) may contribute to the prothrombotic state and may promote the progression of atherosclerosis. We hypothesized that PMPs are elevated in Type 2 diabetes and that patients with Type 2 diabetes and clinically apparent atherosclerosis would have the highest levels. Similarly, we hypothesized that soluble plasma P‐selectin (sPsel) and CD40L (both molecules which are released by activated platelets), as well as %CD62P (P‐selectin) and %CD63 positivity on platelets quantified by flow cytometry, would be highest in patients with Type 2 diabetes and clinically apparent atherosclerotic disease, and might be correlated to PMP levels.

Methods  Venous blood was obtained from 21 Type 2 diabetic patients without atherosclerotic complications, 18 diabetic patients with clinically apparent atherosclerotic disease and 21 non‐diabetic control subjects. PMPs, as well as %CD62P and %CD63 positivity on platelets, were quantified by flow cytometry. sPsel and CD40L were measured using ELISA.

Results   Patients with Type 2 diabetes and clinically apparent atherosclerotic disease had the highest PMP (P = 0.045) and sPsel (P = 0.046) levels, compared with patients without complications (who had intermediate PMP levels) and control subjects. Control subjects had the lowest CD40L levels (P < 0.001) when compared with patients with Type 2 diabetes, with no difference in sCD40L levels between the two diabetic subgroups. %CD62P and %CD63 positivity did not differ between the groups. PMP levels correlated with %CD62P positivity (P = 0.026) but not to %CD63 positivity (P = 0.089), sCD40L (P = 0.407) or sP‐sel (P = 0.163); sCD40L levels did not correlate with any other marker of platelet activation.

Conclusion  PMPs are elevated in Type 2 diabetes. In addition, patients with clinically apparent atherosclerosis had the highest levels of PMPs and sPsel. Thus, PMPs may be a marker of symptomatic atherosclerotic vascular disease in Type 2 diabetes, and may both represent a useful risk stratification tool as well as a novel therapeutic target for anti‐thrombotic drugs.
Interaction of the G182C polymorphism in the APOA5 gene and fasting plasma glucose on plasma triglycerides in Type 2 diabetic subjects
Authors: Jiang Y.‐D. , Yen C.‐J. , Chou W.‐L. , Kuo S.‐S. , Lee K.‐C. , Chiu K. C. , Chuang L.‐M.
Published: August 2005

Aim  Apolipoprotein AV (APOA5) is an important determinant of plasma triglyceride concentration. This study aimed to investigate the relationship of an amino acid substitution at position 182 (G182C) of the apolipoprotein AV (APOA5) gene with triglyceride concentration in a Taiwanese population.

Methods  This study enrolled two cohorts: non‐diabetic subjects (112 males and 89 females) aged 50.3 ± 11.0 years (mean ± sd) and diabetic subjects (106 males and 96 females) aged 62.1 ± 10.3 years. The relationship between the G182C polymorphism (rs 2075291) and plasma triglycerides was examined. Demographic and metabolic parameters including age, sex, body mass index, fasting plasma glucose and total cholesterol were also obtained.

Results  The G182C polymorphism was a determinant of plasma triglycerides in both non‐diabetic (P = 0.022) and diabetic (P = 0.003) groups, independent of age, gender, fasting plasma glucose, body mass index and total cholesterol. In the diabetic group, this genetic polymorphism interacts significantly (P = 0.032) with fasting plasma glucose concentration on plasma triglycerides after adjustment for age, sex, body mass index and total cholesterol.

Conclusions  In conclusion, the G182C polymorphism of the APOA5 gene affects plasma triglycerides in both non‐diabetic and diabetic populations. The observed interaction of gene and glycaemic control further indicates a multifactorial nature of clinical phenotypes in subjects with Type 2 diabetes.

Diabet. Med. (2005)
Hippocampal volume and cognitive performance in long‐standing Type 1 diabetic patients without macrovascular complications
Authors: Lobnig B. M. , Krömeke O. , Optenhostert‐Porst C. , Wolf O. T.
Published: August 2005

Aims  Hippocampal atrophy and memory deficits have been reported in Type 2 diabetes. Whether similar alterations occur in Type 1 diabetes is currently unknown.

Methods  In a case‐control design, 13 Type 1 diabetic patients with at least 10 years’ duration of disease, but free from clinical signs of macrovascular disease, were compared with age‐ and gender‐matched control subjects. Hippocampal volume and measures of global cerebral cerebrospinal fluid (CSF) were determined from magnetic resonance imaging (MRI) scans. Cognitive functions were assessed using four neuropsychological tests. Mood and depression were measured by questionnaires.

Results  Hippocampal volume and memory did not differ between Type 1 diabetic patients and control subjects. However, a significantly increased amount of cerebral CSF suggestive of mild cerebral atrophy was observed in the patients. In addition, deficits in psychomotor speed and selective attention were apparent. Eleven of 13 patients had retinopathy and/or nephropathy. Findings were unrelated to cerebrovascular disease, white matter disease or silent strokes.

Conclusions  Results from our small study in Type 1 diabetic patients do not support findings from previous studies of Type 2 diabetic patients demonstrating reductions in hippocampal volume and impaired memory. On the contrary, we observed evidence for mild cerebral atrophy and impaired psychomotor speed and selective attention. This is in line with some previous studies in Type 1 diabetes. If replicated in larger studies, our findings would support the idea that the effects on brain function and structure differ between Type 1 and Type 2 diabetes.
Examining the relationships between the Pro12Ala variant in PPARG and Type 2 diabetes‐related traits in UK samples
Authors: Zeggini E. , Parkinson J. R C. , Halford S. , Owen K. R. , Walker M. , Hitman G. A. , Levy J. C. , Sampson M. J. , Frayling T. M. , Hattersley A. T. , McCarthy M. I.
Published: August 2005

Aims  The Pro12Ala polymorphism in the PPARG gene alters amino acid sequence and has shown consistent association with susceptibility to Type 2 diabetes in several populations. The present study makes use of large, well‐characterized case‐control resources to enhance understanding of this susceptibility effect by examining related traits, such as body mass index (BMI), waist–hip ratio and age at diagnosis.

Methods  The Pro12Ala variant was genotyped in two UK case samples, ascertained for positive family history and/or early onset of Type 2 diabetes (combined n = 971); and in 1257 ethnically matched control subjects.

Results  There were significant associations of the Pro12Ala single nucleotide polymorphism (SNP) genotypes with diabetes in both case‐control comparisons (P = 0.025 and P = 0.039). Comparing individuals homozygous for the Pro allele, with those carrying an Ala allele, the combined odds ratio for diabetes was 1.40 (95% CIs, 1.12–1.76, P = 0.0031). There was no association between the variant and either waist–hip ratio or age at diagnosis. Proline homozygosity was associated with increased BMI in one patient group (P = 0.013) and decreased BMI in the other (P = 0.038).

Conclusions  This study confirms that variation within PPARG influences susceptibility to Type 2 diabetes in UK samples. However, the relationship between PPARG variation and BMI is more complex, and studies in much larger sample sets will be required to more precisely characterize the effect of this variant on adiposity.
Reported symptoms and quality‐of‐life impacts in patients having laser treatment for sight‐threatening diabetic retinopathy
Authors: Scanlon P. H. , Martin M. L. , Bailey C. , Johnson E. , Hykin P. , Keightley S.
Published: August 2005

Aims  To explore the patient experience of symptoms of eye disease related to diabetes and its treatment, including increase of symptoms over time and their relation to severity of the condition and the effect of multiple treatments and symptoms on quality of life.

Methods  A qualitative interview study was implemented at four eye clinics in the UK. This study design was intended to yield 240 interviews in patients having their first laser treatment or first follow‐up and in multi‐treatment patients with a clinically documented loss of visual function in at least one eye (VA ≤ 6/12). The intention was to have an approximately equal number of patients with proliferative diabetic retinopathy (PDR) or macular oedema (MO).

Results  A total of 227 interviews were completed (54% PDR and 46% MO). The most frequently reported symptom prior to initial treatment was blurred vision (55%). First‐time‐treatment patients reported fewer symptoms than the multi‐treatment patients. After a pronounced reduction of quality‐of‐life impacts after the first laser treatment, results all demonstrate an increasing impact as patients move from first treatment to multiple treatments. The main responses regarding satisfaction with laser treatment were that, although patient expectations were basically met, the treatment had less of an impact than they hoped for, and they would have the treatment again if needed.

Conclusions  The current study provides a qualitative exploration of visual symptoms, levels of self‐reported visual impairment, and general description of the areas of impact or restriction that patients experienced due to their eye disease, both pre‐ and post‐laser treatment.
A NOTE ON KRIPKE's FOOTNOTE 56 ARGUMENT FOR THE ESSENTIALITY OF ORIGIN
Authors: Cameron Ross P.
Published: August 2005

In footnote 56 of his Naming and Necessity, Kripke offers a ‘proof’ of the essentiality of origin. On its most literal reading the argument is clearly flawed, as was made clear by Nathan Salmon. Salmon attempts to save the literal reading of the argument, but I argue that the new argument is flawed as well, and that it can’t be what Kripke intended. I offer an alternative reconstruction of Kripke's argument, but I show that this suffers from a more subtle fault.
Decreases in phosphoinositide‐3‐kinase/Akt and extracellular signal‐regulated kinase 1/2 signaling activate components of spinal motoneuron death
Authors: Newbern J. , Taylor A. , Robinson M. , Li L. , Milligan C. E.
Published: August 2005

Motoneuron dependence on target‐derived trophic factors during development is well established, with loss of trophic support leading to the death of these cells. A complete understanding of the intracellular signal transduction machinery associated with extracellular survival signals requires the examination of individual pathways in various cellular and environmental contexts. In cells deprived of trophic support, and hence compromised for survival, phosphoinositide‐3‐kinase (PI3K) is decreased when compared with healthy cells supplied with trophic support. Extracellular signal‐regulated kinase 1/2 (ERK1/2) signaling is dramatically decreased in deprived cells. We have examined the role of these two pathways to understand how changes in their activity regulate motoneuron survival and death. Pharmacological inhibition of PI3K attenuated motoneuron survival and was important in the regulation of Bcl‐2 serine phosphorylation, limited release of cytochrome c into the cytoplasm and caspase activation. Bax translocation from cytoplasm to mitochondria was not altered when PI3K was inhibited. High levels of ERK1/2 inhibition robustly attenuated motoneuron survival in cells supplied with trophic support, whereas moderate inhibition of ERK1/2 activation had little effect. ERK1/2 inhibition in these cells decreased Bcl‐2 phosphorylation and resulted in release of cytochrome c from the mitochondria. Bax translocation and caspase activation were not affected by ERK1/2 inhibition. These data reveal that changes in PI3K and ERK1/2 signaling lead to individual and overlapping effects on the cell‐death machinery. Characterizing the role of these pathways is critical for a fundamental understanding of the development and degeneration of specific neuronal populations.