bluuebunny/crossref_metadata_2025 huggingface dataset:
GABAB and CB1 cannabinoid receptor expression identifies two types of septal cholinergic neurons
Authors: Nyíri Gábor , Szabadits Eszter , Cserép Csaba , Mackie Ken , Shigemoto Ryuichi , Freund Tamás F.
Published: June 2005

Septohippocampal cholinergic neurons play key roles in learning and memory processes, and in the generation of hippocampal theta rhythm. The range of receptors for endogenous modulators expressed on these neurons is unclear. Here we describe GABAB 1a/b receptor (GABABR) and type 1 cannabinoid receptor (CB1R) expression in rat septal cholinergic [i.e. choline acetyltransferase (ChAT)‐positive] cells. Using double immunofluorescent staining, we found that almost two‐thirds of the cholinergic cells in the rat medial septum were GABABR positive, and that these cells had significantly larger somata than did GABABR‐negative cholinergic neurons. We detected CB1R labelling in somata after axonal protein transport was blocked by colchicine. In these animals about one‐third of the cholinergic cells were CB1R positive. These cells again had larger somata than CB1R‐negative cholinergic neurons. The analyses confirmed that the size of GABABR‐positive and CB1R‐positive cholinergic cells were alike, and all CB1R‐positive cholinergic cells were GABABR positive as well. CB1R‐positive cells were invariably ChAT positive. All retrogradely labelled septohippocampal cholinergic cells were positive for GABABR and at least half of them also for CB1R. These data shed light on the existence of at least two cholinergic cell types in the medial septum: one expresses GABABR and CB1R, has large somata and projects to the hippocampus, whereas the other is negative for GABABR and CB1R and has smaller somata. The results also suggest that cholinergic transmission in the hippocampus is fine‐tuned by endocannabinoid signalling.
The dopamine‐synthesizing cells in the swimming larva of the tunicate Ciona intestinalis are located only in the hypothalamus‐related domain of the sensory vesicle
Authors: Moret Frédéric , Christiaen Lionel , Deyts Carole , Blin Maryline , Joly Jean‐Stéphane , Vernier Philippe
Published: June 2005

Dopamine is a major neuromodulator synthesized by numerous cell populations in the vertebrate forebrain and midbrain. Owing to the simple organization of its larval nervous system, ascidian tunicates provide a useful model to investigate the anatomy, neurogenesis and differentiation of the dopaminergic neural network underlying the stereotypical swimming behaviour of its chordate‐type larva. This study provides a high‐resolution cellular analysis of tyrosine hydroxylase (TH)‐positive and dopamine‐positive cells in Ciona intestinalis embryos and larvae. Dopamine cells are present only in the sensory vesicle of the Ciona larval brain, which may be an ancestral chordate feature. The dopamine‐positive cells of the ascidian sensory vesicle are located in the expression domain of homologues of vertebrate hypothalamic markers. We show here that the larval coronet cells also arise from this domain. As a similar association between coronet cells and the hypothalamus was reported in bony and cartilaginous fishes, we propose that part of the ascidian ventral sensory vesicle is the remnant of a proto‐hypothalamus that may have been present in the chordate ancestor. As dopaminergic cells are specified in the hypothalamus in all vertebrates, we suggest that the mechanisms of dopamine cell specification are conserved in the hypothalamus of Ciona and vertebrates. To test this hypothesis, we have identified new candidate regulators of dopaminergic specification in Ciona based on their expression patterns, which can now be compared with those in vertebrates.
Photoperiod regulates multiple gene expression in the suprachiasmatic nuclei and pars tuberalis of the Siberian hamster (Phodopus sungorus)
Authors: Johnston Jonathan D. , Ebling Francis J. P. , Hazlerigg David G.
Published: June 2005

Photoperiod regulates the seasonal physiology of many mammals living in temperate latitudes. Photoperiodic information is decoded by the master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus and then transduced via pineal melatonin secretion. This neurochemical signal is interpreted by tissues expressing melatonin receptors (e.g. the pituitary pars tuberalis, PT) to drive physiological changes. In this study we analysed the photoperiodic regulation of the circadian clockwork in the SCN and PT of the Siberian hamster. Female hamsters were exposed to either long or short photoperiod for 8 weeks and sampled at 2‐h intervals across the 24‐h cycle. In the SCN, rhythmic expression of the clock genes Per1, Per2, Cry1, Rev‐erbα, and the clock‐controlled genes arginine vasopressin (AVP) and d‐element binding protein (DBP) was modulated by photoperiod. All of these E‐box‐containing genes tracked dawn, with earlier peak mRNA expression in long, compared to short, photoperiod. This response occurred irrespective of the presence of additional regulatory cis‐elements, suggesting photoperiodic regulation of SCN gene expression through a common E‐box‐related mechanism. In long photoperiod, expression of Cry1 and Per1 in the PT tracked the onset and offset of melatonin secretion, respectively. However, whereas Cry1 tracked melatonin onset in short period, Per1 expression was not detectably rhythmic. We therefore propose that, in the SCN, photoperiodic regulation of clock gene expression primarily occurs via E‐boxes, whereas melatonin‐driven signal transduction drives the phasing of a subset of clock genes in the PT, independently of the E‐box.
Occipital (V6) and parietal (V6A) areas in the anterior wall of the parieto‐occipital sulcus of the macaque: a cytoarchitectonic study
Authors: Luppino Giuseppe , Hamed Suliann Ben , Gamberini Michela , Matelli Massimo , Galletti Claudio
Published: June 2005

The anterior wall of the parieto‐occipital sulcus (POs) of the macaque monkey, classically considered as part of Brodmann's area 19, contains two functionally distinct areas: a ventral, purely visual area, V6, and a dorsal area, V6A, containing visual neurons and neurons related to the control of arm movements. The aim of this study was to establish whether areas V6 and V6A, so far identified only on a functional basis, have a cytoarchitectonic counterpart. The cytoarchitectonic analysis of 13 hemispheres from ten macaque brains, cut along different planes of section, showed that the anterior wall of the POs contains three distinct areas. One is located in the ventralmost part of the wall, another in the dorsalmost part of the wall, and the third occupies an intermediate position. The ventralmost region displays architectonic features typical of the occipital cytoarchitectonic domain, whereas the two dorsal areas display architectonic features typical of the posterior parietal cortex. Analysis of myeloarchitecture and of the distribution of SMI‐32 immunoreactivity confirmed the cytoarchitectonic parcellation. Correlation of cytoarchitectonic maps with functional and hodological data strongly suggests that the ventral region corresponds to area V6, whereas the other two regions correspond to different subsectors of V6A, here named V6Av and V6Ad, respectively. The present data are in line with electrophysiological and hodological data, which suggest that area V6 is a classic extrastriate area, whereas V6A is an area of the posterior parietal cortex. They also suggest that V6A includes two separate cortical subdivisions, a view supported by preliminary functional and hodological data that needs further confirmation.
Functional properties of neuronal nicotinic acetylcholine receptors in the chick retina during development
Authors: Lecchi Marzia , McIntosh J. Michael , Bertrand Sonia , Safran Avinoam B. , Bertrand Daniel
Published: June 2005

Acetylcholine (ACh) has been recognized for a long time as a major neurotransmitter in the retina, however, little is known about the contribution of acetylcholine receptors in synaptic processing. Moreover, even less information is available concerning their role during development. To address this question further, we examined the physiological and pharmacological properties of neuronal nicotinic acetylcholine receptors (nAChRs) in retinal ganglion cells from embryonic (E) 12–18‐day‐old Leghorn chicks. Patch‐clamp recordings in whole‐cell configuration revealed that at E12 approximately 21% of the ganglion cells responded to acetylcholine pulses with inward currents. The number of responsive cells progressively increased to 57% at E15 to reach up to 15 positive cells out of 15 cells tested at E18. Acetylcholine‐evoked responses could be subdivided, according to their time course, into fast and slowly desensitizing. Taking advantage of the selectivity of the frog toxin epibatidine (Epi), that preferentially activates heteromeric neuronal nicotinic acetylcholine receptors, we compared the currents evoked by this toxin vs. the effects of acetylcholine. A further characterization of the receptor diversity during development was to assess their sensitivity to the α‐conotoxin MII (α‐CTX‐MII), which has been shown to preferentially block α6‐ and α3β2‐containing receptors. These data demonstrate that ganglion cells of the chick retina express multiple receptor subtypes that progressively develop as a function of retina maturation.
Reduced infarct volume and differential effects on glial cell activation after hyperbaric oxygen treatment in rat permanent focal cerebral ischaemia
Authors: Günther Albrecht , Küppers‐Tiedt Lea , Schneider Philipp‐Moritz , Kunert Ivonne , Berrouschot Jörg , Schneider Dietmar , Roßner Steffen
Published: June 2005

Permanent middle cerebral artery occlusion (MCAO) causes neurodegeneration and a robust activation of glial cells primarily in sensorimotor brain regions of rats. It has been shown that hyperbaric oxygen (HBO) increases oxygen supply to ischaemic areas and reduces neuronal cell loss. The effects of HBO treatment on microgliosis and astrogliosis in permanent cerebral ischaemia have not been addressed so far, but might be critical for neurodegeneration and neuroprotection, respectively. Therefore, we used spontaneously hypertensive rats with permanent MCAO to investigate the time window to start HBO and to compare the effects of different HBO treatment frequencies on infarct volume and on differences with regard to microgliosis and astrogliosis. Seven days after MCAO the infarct volume was calculated from Nissl‐stained brain sections by image analysis. HBO significantly decreased the infarct volume when used as early as 15, 90 or 180 min post‐MCAO by 24%, 16% and 13%, respectively, in the single‐treatment group. Repetitive HBO treatment (first HBO session 90 min after MCAO) was not effective. Microglial cells and astrocytes were detected by cytochemical fluorescent labelling and confocal laser scanning microscopy. In the single‐treatment group we observed significantly higher astrocyte immunoreactivity but decreased microglial density in the peri‐infarct region. These effects of HBO treatment on glial cells were not present in rats where HBO did not reduce the infarct volume (360 min after MCAO). Our data indicate that HBO‐induced suppression of microgliosis and aggravated response of astrocytes might contribute to the reported beneficial effects of early HBO treatment in cerebral ischaemia.
Knowing good from bad: differential activation of human cortical areas by positive and negative outcomes
Authors: Nieuwenhuis Sander , Slagter Heleen A. , Von Geusau Niels J. Alting , Heslenfeld Dirk J. , Holroyd Clay B.
Published: June 2005

Previous research has identified a component of the event‐related brain potential (ERP), the feedback‐related negativity, that is elicited by feedback stimuli associated with unfavourable outcomes. In the present research we used event‐related functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) recordings to test the common hypothesis that this component is generated in the caudal anterior cingulate cortex. The EEG results indicated that our paradigm, a time estimation task with trial‐to‐trial performance feedback, elicited a large feedback‐related negativity (FRN). Nevertheless, the fMRI results did not reveal any area in the caudal anterior cingulate cortex that was differentially activated by positive and negative performance feedback, casting doubt on the notion that the FRN is generated in this brain region. In contrast, we found a number of brain areas outside the posterior medial frontal cortex that were activated more strongly by positive feedback than by negative feedback. These included areas in the rostral anterior cingulate cortex, posterior cingulate cortex, right superior frontal gyrus, and striatum. An anatomically constrained source model assuming equivalent dipole generators in the rostral anterior cingulate, posterior cingulate, and right superior frontal gyrus produced a simulated scalp distribution that corresponded closely to the observed scalp distribution of the FRN. These results support a new hypothesis regarding the neural generators of the FRN, and have important implications for the use of this component as an electrophysiological index of performance monitoring and reward processing.
Identification, characterization and phylogenetic signal of an elongation factor‐1 alpha fragment in demosponges (Metazoa, Porifera, Demospongiae)
Authors: Erpenbeck Dirk , Breeuwer Johannes A. J. , Van Soest Rob W. M.
Published: June 2005

Erpenbeck, D., Breeuwer, J.A.J. & van Soest, R.W.M. (2005). Identification, characterization and phylogenetic signal of an elongation factor‐1 alpha fragment in demosponges (Metazoa, Porifera, Demospongiae). —Zoologica Scripta, **, *** – ***.

Independent molecular markers are needed in order to clarify demosponge systematics. Elongation factor‐1 alpha (EF‐1a) is a frequently used marker in metazoan phylogeny, which has not hitherto been used for Porifera. In this paper, a fragment of the gene encoding EF‐1a is characterized and tested for its suitability in phylogenetic reconstructions of demosponges. We point out the pitfalls in establishing new markers in sponge molecular systematics, particularly with regard to the variety of nonporiferan DNA templates contained within sponges, and show the limited suitability of the fragment for higher demosponge systematics.
A new cryptic species of pond turtle from southern Italy, the hottest spot in the range of the genus Emys (Reptilia, Testudines, Emydidae)
Authors: Fritz Uwe , Fattizzo Tiziano , Guicking Daniela , Tripepi Sandro , Pennisi Maria Grazia , Lenk Peter , Joger Ulrich , Wink Michael
Published: June 2005

Geographic variation in the mtDNA haplotypes (cytochrome b gene) of 127 European pond turtles from Italy was investigated. Thirty‐eight of the Italian samples were also studied by nuclear fingerprinting (ISSR PCR) and compared with samples from other parts of the range representing all nine currently known mtDNA lineages of Emys orbicularis. Our genetic findings were compared against morphological data sets (measurements, colour pattern) for 109 adult turtles from southern Italy. Italy is displaying on a small geographical scale the most complicated variation known over the entire distributional area of Emys (North Africa over Europe and Asia Minor to the Caspian and Aral Seas). The Tyrrhenic coast of the Apennine Peninsula, the Mt. Pollino area and Basilicata are inhabited by Emys orbicularis galloitalica, a subspecies harbouring a distinct mtDNA lineage. The same lineage is also found in Sardinia. Along the Adriatic coast of Italy and on the Salentine Peninsula (Apulia, southern Italy), another morphologically distinctive subspecies (Emys orbicularis hellenica) occurs, which also bears a different mtDNA lineage. A higher diversity of mtDNA haplotypes in the south of the Apennine Peninsula suggests that the glacial refugia of E. o. galloitalica and E. o. hellenica were located here. A further refuge of E. o. hellenica probably existed in the southern Balkans. The west coasts of the Balkans and Corfu have probably been colonized from Italy and not from the geographically closer southern Balkanic refuge. In Sicily, a third mtDNA lineage is distributed, which is sister to all other known lineages of Emys. Morphologically, Sicilian pond turtles resemble E. o. galloitalica. However, nuclear fingerprinting revealed a clear distinctiveness of the Sicilian taxon, whereas no significant divergence was detected between representatives of the other eight mtDNA lineages of Emys. Furthermore, nuclear fingerprinting provided no evidence for current or past gene flow between the Sicilian taxon and the mainland subspecies of E. orbicularis. Therefore, Sicilian pond turtles are described here as a species new to science. Some populations in Calabria and on the Salentine Peninsula comprise individuals of different mtDNA lineages. We interpret this as a natural contact. However, we cannot exclude that these syntopic occurrences are the result of human activity. For example, in other parts of Italy, the natural distribution pattern of Emys is obscured by allochthonous turtles. This could also be true for southern Italy. The discovery of the complex taxonomic differentiation in southern Italy requires reconsidering conservation strategies.
Revision and phylogenetic analysis of Americanethicusandrupununigroups ofAnelosimus(Araneae, Theridiidae)
Authors: Agnarsson Ingi
Published: June 2005

Two species groups of the social spider genusAnelosimusare revised. Theethicusgroup contains six species found in South America, in an area ranging from the Guianas to southern Brazil and Argentina. Of these,A. rabusLevi, 1963,A. ethicus(Keyserling, 1884), andA. nigrescens(Keyserling, 1884) are redescribed, whileA. nigrescensis removed from synonymy withA. ethicus. Three new species are described:A. misionessp. nov.,A. sumisolenasp. nov. andA. inhandavasp. nov.Anelosimus ethicusis reportedly either subsocial or solitary, while the behaviour of the other species in the group is unknown. Therupununigroup contains two quasisocial species,A. rupununiLevi, 1956 andA. lorenzoFowler & Levi, 1979, from the Caribbean and tropical South America. Both are redescribed here. A parsimony analysis of morphological characters provides support for the monophyly of both groups. In the phylogeny, subsociality optimizes to the base ofAnelosimus, indicating that the common ancestor of theethicusgroup was subsocial. Its members can thus be predicted to be subsocial, or secondarily solitary. Quasisociality arosede novoin therupununigroup, representing one of 6−7 independent origins in theridiids. Study of the biology ofAnelosimusis important to advance our understanding of the evolution of sociality in spiders.
Molecular phylogeny of gill monogeneans (Platyhelminthes, Monogenea, Dactylogyridae) and colonization of Indo‐West Pacific butterflyfish hosts (Perciformes, Chaetodontidae)
Authors: Plaisance Laetitia , Littlewood D. Timothy J. , Olson Peter D. , Morand Serge
Published: June 2005

We investigated the phylogenetic relationships among monogenean parasites of the Chaetodontidae (butterflyfishes) from the Indo‐West Pacific Ocean. Molecular phylogenies of selected taxa within the Dactylogyridae, including the ancyrocephaline parasites of butterflyfishes, based on two nuclear and one mitochondrial gene fragments (complete 18S rDNA, partial 28S rDNA (D1‐D3), and partial 16S rDNA) were reconstructed using parsimony, maximum likelihood and Bayesian inference methods. Our results show the non‐monophyletic nature of the monogenean fauna of butterflyfishes. The group is divided into two independent lineages. The first clade contains species of the genera Aliatrema and Euryhaliotrematoides, which parasitize Chaetodontidae exclusively. The second contains species of Haliotrema, a generalist group of parasites. The positions of several other species of the Ancyrocephalinae, including freshwater species, at the base of the two clades, provide strong evidence that the monogenean fauna did not result from a single colonization event, but rather that they have colonized their butterflyfish hosts independently at least twice.
Phylogenetic review of the Chinese species ofAcanthacorydalis(Megaloptera, Corydalidae)
Authors: Liu Xing Yue , Yang Ding , Ge Si Qin , Yang Xing Ke
Published: June 2005

The dobsonfly genusAcanthacorydalisWeele is a small genus which only occurs in Asia and comprises eight species. Seven species are restricted to the Oriental realm, whileA. orientalis(McLachlan) extends into the Palaearctic realm. There are five species in China, four of which are endemic. In the present paper, the Chinese species are redescribed, illustrated, keyed, and subjected to phylogenetic and biogeographical analyses for the first time. Geographic distributions are updated. The cladistic analysis for the Chinese species was constructed by using Hennig86, based on 17 adult morphological characters. The phylogenetic relationships obtained are (A. orientalis+A. yunnanensis+A. unimaculata+ (A. fruhstorferi+A. sinensis)). Six areas of endemism are identified based onAcanthacorydalisdistributions: north, south‐west, central and south China, north‐eastern India and northern Vietnam.
Microanatomy of the radius and lifestyle in amniotes (Vertebrata, Tetrapoda)
Authors: Germain Damien , Laurin Michel
Published: June 2005

Radial cross‐sections of 49 species of extant and two species of extinct amniotes of known lifestyle have been studied in order to assess the relationship between lifestyle (aquatic, amphibious or terrestrial) and bone microanatomy. Most compactness profile and body size parameters exhibit a phylogenetic signal; therefore, classical statistical tests should not be used. Permutational multiple linear regressions show an ecological signal in most compactness profile parameters and in the cross‐section maximal diameter. A linear discriminant analysis is performed with these parameters to distinguish the various lifestyles. The discriminant function based on taxa of known lifestyle is used to infer the lifestyle of three extinct amniotes: the early nothosaurPachypleurosaurus(amphibious), the therapsidLystrosaurus(amphibious) and the synapsidOphiacodon(aquatic). These predictions are congruent with classical palaeoecological interpretations. This model may be very useful when attempting to infer the ancestral lifestyle of amniotes and other early limbed vertebrates.
Evaluation of ITS rDNA as a complement to mitochondrial gene sequences for phylogenetic studies in freshwater mussels: an example using Unionidae from north‐western Europe
Authors: Källersjö Mari , Von Proschwitz Ted , Lundberg Stefan , Eldenäs Pia , Erséus Christer
Published: June 2005

Mitochondrial inheritance in the Unionidae is complex since mitochondria can be inherited from both parents. An increased rate of recombination could lead to erroneous homology assessments, which could cause problems for phylogenetic reconstruction. For this reason we investigated the possibility of using a nuclear marker, the ribosomal internal transcribed spacer region, for phylogenetic studies in the Unionidae, as a complement and comparison to two of the most widely used mitochondrial genes today. The nuclear ribosomal internal transcribed spacer region (ITS1, 5.8S, ITS2) was sequenced from 72 specimens representing six of the seven species of Unionidae mussels occurring in NW Europe: Unio pictorum, U. tumidus, U. crassus, Anodonta anatina, A. cygnea and Pseudanodonta complanata. Sequences from Margaritifera margaritifera were used as an outgroup. The ITS sequences of all species were found to have low intragenomic and infraspecific variation. Compared to mitochondrial genes (16S and COI) they show an intermediate genetic diversity. Phylogenetic analyses produce tree topologies that are congruent with those resulting from analyses of the mitochondrial sequences. Likewise, an incongruence length difference (ILD) test showed no significant incongruence between data sets, indicating that if recombination has occurred it has not produced any conflicting patterns. Best‐resolved and supported trees are obtained when gaps are treated as a fifth character state. A combined analysis of the three gene regions shows that Unio crassus and U. pictorum are more closely related than either to U. tumidus. Pseudanodonta is nested within Anodonta as sister taxon to A. cygnea. Advice on how to best preserve mussel material for DNA studies is provided.
Screening for diabetes in Indigenous populations using glycated haemoglobin: sensitivity, specificity, post‐test likelihood and risk of disease
Authors: Rowley K. G. , Daniel M. , O'Dea K.
Published: June 2005

Aims  Screening for diabetes using glycated haemoglobin (HbA1c) offers potential advantages over fasting glucose or oral glucose tolerance testing. Current recommendations advise against the use of HbA1c for screening but test properties may vary systematically across populations, according to the diabetes prevalence and risk. We aimed to: (i) characterize the properties of test cut‐offs of HbA1c for diagnosis of diabetes relative to a diagnosis based on a fasting plasma glucose concentration of 7.0 mmol/l for high‐risk Indigenous populations; and (ii) examine test properties across a range of diabetes prevalence from 5 to 30%.

Methods  Data were collected from Aboriginal and Torres Strait Islander communities in Australia and a Canadian First Nations community (diabetes prevalence 12–22%) in the course of diabetes diagnostic and risk factor screening programmes (n = 431). Screening test properties were analyzed for the range of HbA1c observed (3–12.9%).

Results  In separate and pooled analyses, a HbA1c cut point of 7.0% proved the optimal limit for classifying diabetes, with summary analysis results of sensitivity = 73 (56–86)%, specificity = 98 (96–99)%, overall agreement (Youden's index) = 0.71, and positive predictive value (for an overall prevalence of 18%) = 88%. For diabetes prevalence from 5 to 30% the post‐test likelihood of having diabetes given HbA1c = 7.0% (positive predictive value) ranged from 62.7 to 93.2%; for HbA1c < 7.0%, the post‐test likelihood of having diabetes ranged from 4.5 to 27.7%.

Conclusions  The results converge with research on the likelihood of diabetes complications in supporting a HbA1c cut‐off of 7.0% in screening for diabetes in epidemiological research. Glycated haemoglobin has potential utility in screening for diabetes in high‐risk populations.
An assessment of the coverage of a district‐wide diabetic retinopathy screening service
Authors: Buch H. N. , Barton D. M. , Varughese G. I. , Bradbury S. , Scarpello J. H. B. , Walker A. B.
Published: June 2005

Aims  To assess the coverage of the diabetes retinopathy screening service (DRSS) in North Staffordshire, to identify patient characteristies associated with non‐attendance and to assess the proportion of patients with diabetic retinopathy who achieved glycaemic and blood pressure (BP) control targets.

Methods  Data for all patients who underwent annual retinal screening between 1 May 2000 and 30 April 2001 were obtained from the North Staffordshire Diabetes Register. Age, gender, ethnicity, socio‐economic status, type and duration of diabetes were compared between patients who underwent eye screening and those who did not. Frequencies of patients who achieved glycaemic and BP targets in these groups of patients were compared to the remaining patients.

Results  5646 of the 11682 (48%) patients on the diabetes register underwent retinal screening during the year. Patients with Type 2 diabetes, older patients, patients belonging to ethnic minorities and those wholly managed in primary care were less likely to attend for eye screening (P < 0.05 for all groups) with ethnic minority or primary care management demonstrating independent influence (P < 0.001). The percentage of patients with retinopathy achieving HbA1c and systolic BP targets was significantly lower than in their unaffected counterparts (χ2 = 63, P < 0.001 and χ2 = 71, P < 0.001 respectively).

Conclusions  The efficacy of the DRSS in North Staffordshire is low and might be improved by targeting specific patient groups. Glycaemic control and systolic BP control needs to be improved in patients with diabetic retinopathy.
Depression in Croatian Type 2 diabetic patients: prevalence and risk factors. A Croatian survey from the European Depression in Diabetes (EDID) Research Consortium
Authors: Pibernik‐Okanovic M. , Peros K. , Szabo S. , Begic D. , Metelko Z.
Published: June 2005

Aims  To determine the prevalence rate of and risk factors for depression in Croatian Type 2 diabetic patients.

Methods  Depressive mood was examined in 384 randomly selected outpatients with Type 2 diabetes. Center for Epidemiological Studies Depression Scale (CES‐D) and Structured Clinical Interview for DSM‐IV Axis I Disorders (SCID) were used to identify depressive disturbances. The groups with CES‐D ≥ 16 and < 16 were compared with respect to demographic, psychological and clinical characteristics. Regression analysis was used to determine risk factors for depression.

Results  Of the examined patients, 22% had CES‐D scores ≥ 16, and in 33% of them clinical depression was confirmed by the psychiatric interview. Depressed patients compared with the non‐depressed ones reported more diabetes‐related problems and poorer well‐being (t = 6.71, P < 0.001 and t = 11.98, P < 0.001, respectively). Multiple regression analysis indicated female gender, experienced support and the level of emotional well‐being to predict depression (R = 0.74, F = 15.3, P < 0.001).

Conclusions  The obtained data indicate that the prevalence rate in Croatian Type 2 diabetic patients is comparable to findings from other cultural settings. Depressive symptoms can be predicted by psychological rather than disease‐related variables. Psychological care for diabetic patients may be necessary to prevent depressive symptomatology.
Indications and efficacy of continuous subcutaneous insulin infusion (CSII) therapy in Type 1 diabetes mellitus: a clinical audit in a specialist service
Authors: Rodrigues I. A. S. , Reid H. A. , Ismail K. , Amiel S. A.
Published: June 2005

Aim  To determine if current guidelines correctly identify patients who will benefit from continuous subcutaneous insulin infusion (CSII) therapy by comparing outcomes between Type 1 diabetic patients with recurrent severe hypoglycaemia (SH) indications with those without; and between patients without and with classic contraindications to CSII managed in a single multidisciplinary pump clinic.

Methods  Changes in biomedical outcomes [glycated haemoglobin (HbA1c), hypoglycaemia, diabetic ketoacidosis (DKA) rates], from before CSII to the end of the study (median duration 20.5 months, range 1–192), were analysed retrospectively from data collected from notes and interviews of 40 patients. Quality of life was assessed by three validated questionnaires at study end (33 patients).

Results  Twenty‐five out of forty patients were started for reasons other than SH and 15 out of 40 had contraindications to CSII. Overall, CSII was associated with a reduction in HbA1c (9.6 ± 2.7% to 8.3 ± 1.2%, P = 0.011), SH (6.45 ± 16.15/year to 0.34 ± 1.01/year, P = 0.034) and DKA (1.83 ± 4.48/year to 0.27 ± 1.12/year, P = 0.036). The fall in SH was greater for patients started for SH (P < 0.001). However, only patients started for other indications showed a fall in HbA1c (P = 0.001). The fall in DKA rate was greater in patients with contraindications (P = 0.042), and they did not lose the other benefits of CSII therapy, including quality of life.

Conclusions  In the setting of a specialist multidisciplinary service, CSII can be an effective and safe therapy. It confers benefit outside the setting of severe hypoglycaemia and can confer benefit in some patients with classic contraindications. This questions the validity of criteria that may exclude these patients in such a service.
Association of C‐reactive protein with body fat, diabetes and coronary artery disease in Asian Indians: The Chennai Urban Rural Epidemiology Study (CURES‐6)
Authors: Mohan V. , Deepa R. , Velmurugan K. , Premalatha G.
Published: June 2005

Objective  The aim of the study was to determine the association of high sensitivity C‐reactive protein (hs‐CRP) with body fat, diabetes and coronary artery disease (CAD) in an urban south Indian population.

Design  The study was conducted on 150 subjects selected from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing population‐based study on a representative population of Chennai (formerly Madras). Group 1 comprised of non‐diabetic subjects without CAD (n = 50). Type 2 diabetic subjects without CAD formed Group 2 (n = 50); Group 3 comprised of Type 2 diabetic subjects with CAD (n = 50). CAD was diagnosed based on electrocardiographic (ECG) changes suggestive of ST segment depression and/or Q wave changes using appropriate Minnesota codes. All study subjects were non‐smokers, and had no infectious or inflammatory diseases. The plasma levels of hs‐CRP were measured using a highly sensitive nephelometric assay. Body fat was calculated using Siri's formula using skin fold measurements.

Results  Diabetic subjects with (2.89 mg/l) and without (2.25 mg/l) CAD had significantly higher hs‐CRP levels compared with non‐diabetic subjects without CAD (0.99 mg/l, P < 0.001). hs‐CRP values increased with increases in tertiles of body fat (anovaP < 0.001) and HbA1c (anovaP < 0.001). Multiple logistic regression analysis revealed hs‐CRP to be strongly associated with CAD (OR: 1.649, P = 0.040) and diabetes (OR: 2.264, P = 0.008) even after adjusting for age and gender. Regression analysis also revealed body fat to be strongly associated with diabetes and CAD even after adjusting for age and gender (P < 0.001). hs‐CRP influenced this association for diabetes but not for CAD.

Conclusion  hs‐CRP showed a strong association with CAD and diabetes, even after adjusting for age and gender. The association of body fat with diabetes seems to be mediated through hs‐CRP. However, hs‐CRP does not appear to mediate the relationship between body fat and CAD.
Prospective screening for biopsy proven coeliac disease, autoimmunity and malabsorption markers in Belgian subjects with Type 1 diabetes
Authors: Buysschaert M. , Tomasi J. P. , Hermans M. P.
Published: June 2005

Aims  To determine prospectively the prevalence of biopsy proven coeliac disease (CD) in an adult Type 1 diabetic population from Belgium with regards to associated auto‐immunity and malabsorption.

Methods and results  Determination in 400 Type 1 diabetic patients of serum anti‐endomysial and/or anti‐transglutaminase auto‐antibodies. All subjects with abnormal serology underwent an intestinal biopsy. Ten patients (2.5%) had positive antibodies. Diagnosis of CD was confirmed by an intestinal biopsy. Eight patients were symptom‐free, although laboratory findings suggesting malabsorption were prominent in the presence of CD [microcytic anaemia, iron and folate deficiencies, low levels of 25(OH)vitamin D3, calcium and cholesterol]. Other auto‐immune conditions, especially vitiligo, were found in patients with CD.

Conclusions  Asymptomatic coeliac disease occurs frequently in adult Type 1 diabetic patients, and is often associated with subclinical malabsorption. Screening should be part of routine evaluation, to implement life‐long dietary gluten avoidance.
Impaired vascular function during short‐term poor glycaemic control in Type 1 diabetic patients
Authors: Sørensen V. R. , Mathiesen E. R. , Clausen P. , Flyvbjerg A. , Feldt‐Rasmussen B.
Published: June 2005

Aim  To study the effects of short‐term poor glycaemic control on vascular function in Type 1 diabetic patients.

Methods  Ten Type 1 diabetic patients, with diabetes duration of less than 10 years and normal urinary albumin excretion and ophthalmoscopy, were studied. All patients were examined after 48 h of good vs. poor glycaemic control within a 3‐week period. Blood glucose was measured seven times daily for 2 days before each examination. External ultrasound was used to measure the dilatory response of the brachial artery to post‐ischaemic increased blood flow (endothelium‐dependent dilation) and to nitroglycerin (endothelium‐independent dilation). Plasma concentration of von Willebrand factor antigen, adhesion molecules, vascular endothelial growth factor, homocystein and cholesterol were also measured.

Results  The median blood glucose levels in the 48 h before the examinations were [median (range), good vs. poor control]: 6.3 (5.0–7.6) vs. 15.9 (11.3–17.8) (mmol/l). The flow‐associated vasodilation (% of baseline) was reduced during poor control: 102.7 (94.7–110.8) vs. 104.0 (99.6–118.5) (P < 0.05) as were the nitroglycerin‐induced dilation (% of baseline): 114.5 (103.3–127.9) vs. 120.2 (106.8–148.0) (P < 0.05). P‐von Willebrand factor antigen was high during poor control (kIU/l): 1.14 (0.73–1.84) vs. 0.86 (0.72–1.39) (P < 0.05) and so was P‐vascular endothelial growth factor (ng/l): 288 (133–773) vs. 254 (90–383) (P < 0.05).

Conclusions  Short‐term (48 h) hyperglycaemia in Type 1 diabetic patients may disturb vascular function, possibly mediated through smooth muscle cell dysfunction as well as endothelial dysfunction. We suggest that prolonged and repeated episodes of hyperglycaemia could possibly lead to permanent vascular dysfunction and thereby development and progression of vascular complications in diabetes.
Physical activity and energy intake in adolescent girls with Type 1 diabetes
Authors: Särnblad S. , Ekelund U. , Åman J.
Published: June 2005

Aims  Girls with Type 1 diabetes often gain excessive weight during puberty. The aims of this study were to compare objectively assessed physical activity and energy intake in girls with Type 1 diabetes with those in healthy age‐matched controls.

Methods  This prospective cohort study comprised 26 girls with Type 1 diabetes and 49 control girls. The mean age of the diabetic girls was 15.7 ± 2.1 years and that of the control girls 15.8 ± 2.1 years. In the diabetic group, mean haemoglobin A1c was 7.6 ± 1.4% and daily insulin dosage was 1.1 ± 0.3 U/kg. Physical activity was measured during 7 consecutive days with a uniaxial accelerometer, and energy intake was assessed concurrently with a 7‐day food diary.

Results  There was a tendency towards lower total amount of physical activity in the diabetes group but the difference between the study groups did not reach statistical significance (Diabetes: 464 ± 123 counts/min/day; Controls: 523 ± 138 counts/min/day; P = 0.06). No difference was found between the groups regarding total energy intake (Diabetes: 8.5 ± 1.8 MJ/day; Controls: 8.4 ± 2.6 MJ/day). The carbohydrate intake was lower and the protein and fibre intakes were higher in girls with diabetes. No association was observed between physical activity, energy intake and HbA1c.

Conclusions  In this prospective cohort study, we found a tendency towards lower physical activity but no differences in energy intake between girls with Type 1 diabetes and age‐matched controls. Larger studies are needed to further explore the importance of the total amount of physical activity for excessive weight gain in adolescent girls with Type 1 diabetes.
Comparison of three multiple injection regimens for Type 1 diabetes: morning plus dinner or bedtime administration of insulin detemir vs. morning plus bedtime NPH insulin
Authors: Pieber T. R. , Draeger E. , Kristensen A. , Grill V.
Published: June 2005

Aims  This trial investigated the efficacy and safety of two different administration‐time regimens with insulin detemir (IDet) to that of a conventional basal insulin regimen with NPH insulin (NPH).

Methods  This multinational, 16‐week, open, parallel group trial included 400 people with Type 1 diabetes mellitus (DM) randomized to IDet either morning and before dinner (IDetmorn+din) or morning and bedtime (IDetmorn+bed), or to NPH morning and bedtime (NPHmorn+bed), all in combination with mealtime insulin aspart (IAsp).

Results  HbA1c was comparable between the three groups after 16 weeks (P = 0.64), with reductions of 0.39–0.49% points. Lower fasting plasma glucose (FPG) was observed with IDetmorn+din and IDetmorn+bed compared with NPHmorn+bed (9.8 and 9.1 vs. 11.1 mmol/l, P = 0.006), whereas the IDet groups did not differ (P = 0.15). Within‐person variation in self‐measured FPG was significantly lower for both IDet regimens (sd IDetmorn+din 2.5, IDetmorn+bed 2.6 mmol/l) than for NPHmorn+bed (sd 3.1 mmol/l, P < 0.001), but was comparable between the IDet groups (P = 0.48). Ten‐point plasma glucose profiles were lower between dinner and breakfast in the IDetmorn+din group (P = 0.043), compared with the two other groups. Risk of overall and nocturnal hypoglycaemia was similar for the three groups. Lower mean bodyweight was observed with IDet compared with NPH after 16 weeks (difference: IDetmorn+din−1.3 kg, P < 0.001, IDetmorn+bed−0.6 kg, P = 0.050).

Conclusions  Both IDet regimens were well tolerated and provided lower and less variable glucose levels with no, or less, weight gain than NPH at comparable HbA1c. IDet can be administered either at dinner or bedtime, with similar glycaemic control according to the need of the individual person.

Pieber T R, Grill V, Kristensen A, Draeger E: Treatment with insulin detemir allows flexible timing of administration in subjects with Type 1 diabetes. Diabetes 2003; 52 (Suppl. 1): A130.
Self‐monitoring of blood glucose in non‐insulin‐treated diabetic patients: a longitudinal evaluation of its impact on metabolic control
Authors: Franciosi M. , Pellegrini F. , De Berardis G. , Belfiglio M. , Di Nardo B. , Greenfield S. , Kaplan S. H. , Rossi M. C. E. , Sacco M. , Tognoni G. , Valentini M. , Nicolucci A.
Published: June 2005

Aims  In the framework of a nationwide outcomes research programme, we assessed the impact of self‐monitoring of blood glucose (SMBG) on metabolic control over 3 years in patients with Type 2 diabetes mellitus (DM2) not treated with insulin.

Methods  The study involved 1896 patients who completed, at 6‐month intervals for 3 years, a questionnaire investigating SMBG practice. Clinical information was collected by participating clinicians at the same time intervals. The predictive value of SMBG frequency on long‐term metabolic control was estimated using multilevel analysis. The impact of SMBG on metabolic control was also evaluated in distinct and homogeneous subgroups of patients showing different likelihood of performing SMBG, identified using a tree‐growing technique (RECPAM).

Results  Overall, 22% of the patients were on diet alone and 78% were treated with oral agents; 41% practiced SMBG ≥ 1/week (10.3%≥ 1/day). The analysis of metabolic control according to the frequency of SMBG failed to show any significant impact of this practice on HbA1c levels over 3 years. Similarly, changes in SMBG frequency during the study were not related to significant changes in HbA1c levels. RECPAM analysis led to the identification of eight classes, characterized by substantial differences in the likelihood of performing SMBG with a frequency of at least 1/week. Nevertheless, in none of the RECPAM classes identified, did SMBG predict a better metabolic control over 3 years of follow‐up. In those RECPAM classes indicating that SMBG was mainly performed to avoid hypoglycaemic episodes, SMBG was associated with a decrease in the frequency of hypoglycaemic episodes during the study.

Conclusions  In a large sample of non‐insulin‐treated Type 2 diabetic patients, the performance and frequency of SMBG did not predict better metabolic control over 3 years. We could not identify any specific subgroups of patients for whom SMBG practice was associated with lower HbA1c levels during the study.
Studies of relationships between the GLUT10 Ala206Thr polymorphism and impaired insulin secretion
Authors: Rose C. S. , Andersen G. , Hamid Y. H. , Glümer C. , Drivsholm T. , Borch‐Johnsen K. , Jørgensen T. , Pedersen O. , Hansen T.
Published: June 2005

Aims  This study aimed to investigate if the previously observed association between the GLUT10 Ala206Thr polymorphism and variation in fasting and oral glucose‐induced serum insulin concentrations could be replicated in a large‐scale population‐based cohort of Danish whites.

Methods  The GLUT10 Ala206Thr polymorphism was genotyped in a case‐control study of 880 Type 2 diabetic patients and 4372 glucose‐tolerant control subjects. The latter group was also enrolled in an assessment of fasting and post‐OGTT circulating levels of plasma glucose and serum insulin in relation to genotype. The variant was genotyped by analysis of PCR‐generated primer extension by matrix‐assisted laser desorption/ionization time‐of‐flight analysis.

Results  The Ala206Thr variant was equally frequent among Type 2 diabetic patients and glucose‐tolerant subjects (P = 0.9) and there was no difference in the distribution of genotype groups (P = 1.0). In the 4372 glucose‐tolerant subjects there was no statistically significant association between the polymorphism and levels of fasting and post‐oral glucose tolerance test plasma glucose and serum insulin along with the insulinogenic index and the homeostasis model of assessment for insulin resistance and insulin secretion. Likewise, in an age‐stratified subgroup comprising 1264 subjects, we observed no relationships between the GLUT10 polymorphism and the selected metabolic features.

Conclusions  The GLUT10 Ala206Thr polymorphism is not associated with Type 2 diabetes in the Danish population. Furthermore, in the present large‐scale cohort, the polymorphism does not associate with phenotypes such as fasting and oral glucose‐induced levels of plasma glucose and serum insulin.
Lower plasma triglycerides are associated with increased need for insulin requirement in poorly controlled Type 2 diabetic patients
Authors: Rigalleau V. , Baillet‐Blanco L. , Perlemoine C. , Salmi L.‐R. , Gin H.
Published: June 2005

Aims  To identify factors associated with insulin requirement in Type 2 diabetic patients, and to examine the significance of a normal plasma triglyceride level.

Methods  One hundred and three poorly controlled (HbA1c = 9.4 ± 1.9%) Type 2 diabetic patients initially not treated with insulin were followed up for 5 years. Insulin was administered if HbA1c > 8% despite maximal oral anti‐diabetic treatment and bodyweight control. Variables were compared between insulin requiring and non‐insulin‐treated patients using unpaired t‐tests. The outcomes of initially normotriglyceridaemic (< 1.7 mmol/l) and hypertriglyceridaemic patients were compared using unpaired t‐tests, and a survival analysis (Cox proportional hazards model).

Results  Sixty‐three patients were transferred to insulin. They were 5 years older (P = 0.004), with a 3‐year longer duration of their diabetes (P = 0.03), a 1.2% higher HbA1c (P = 0.002), and 50% lower triglyceride levels (P = 0.02) than the others. The survival analysis showed that a long duration of diabetes, a high HbA1c, and a normal triglyceride level were associated with the need for insulin; the effect of normotriglyceridaemia was significant in the most poorly controlled (HbA1c > 9.5%) patients (relative risk: 2.35, 95% confidence interval: 1.16–5.52, P = 0.016). The 46 normotriglyceridaemic patients were leaner (P = 0.0004) and had lower C‐peptide levels (P = 0.0008) than the others. Despite similar diabetes duration and HBA1c, more were transferred to insulin (normotriglyceridaemic: 71%, hypertriglyceridaemic: 52%, P = 0.03).

Conclusion  A normal triglyceride level is associated with a need for insulin in poorly controlled Type 2 diabetes.