bluuebunny/crossref_metadata_2025 huggingface dataset:
Prandial regulation of ghrelin secretion in humans: does glucagon contribute to the preprandial increase in circulating ghrelin?
Authors: Soule Steven , Pemberton Chris , Hunt Penny , Cole David , Raudsepp Sara , Inder Warrick
Published: September 2005

Objective  Glucagon secretion is stimulated by fasting and inhibited postprandially, a pattern that mimics the secretory profiles of both ghrelin and GH. We thus hypothesized that glucagon may be a determinant of the changes in circulating ghrelin and GH that occur in relation to meals. The objective of the study was to explore this hypothesis by determining the ghrelin and GH response to a bolus of glucagon or saline in healthy subjects.

Subjects and measurements  Nine healthy volunteers, mean age 47 years (range 33–58) and body mass index (BMI) 24 kg/m2 (range 20·9–27·6) were recruited and received either 1 mg glucagon (n = 9) or 1 ml saline (n = 6) subcutaneously on separate days between 0800 and 0830 h after an overnight fast. Venous blood was then sampled at 15‐min intervals during the first hour, followed by 30‐min intervals up to 4 h for glucose, insulin, GH, cortisol, somatostatin and ghrelin.

Results  Mean ± SE basal ghrelin was 213·1 ± 34·3 pmol/l and decreased significantly by 15 min after glucagon administration to 179·3 ± 28 pmol/l (P = 0·01), then remaining suppressed relative to the basal value until 240 min after glucagon. Plasma insulin increased from a basal value of 46·7 ± 7·7 pmol/l to a peak of 327·1 ± 54·9 pmol/l (P < 0·0001). There was an inverse statistical relationship between the increase in insulin over the first 120 min and the decrease in ghrelin (P = 0·005), while somatostatin, GH and glucose were not significant contributors to the decrease in ghrelin (P > 0·05). Mean ± SE basal GH was 7·3 ± 2·9 µg/l and increased by 150 min after glucagon to a peak of 20·5 ± 6·8 µg/l (P = 0·006). Changes in neither ghrelin nor glucose were related to the increase in GH (P = 0·7). Saline administration did not produce any significant change in ghrelin, insulin or somatostatin although the expected diurnal reduction in cortisol (P < 0·05) was observed.

Conclusions  Our study found no evidence that glucagon stimulates ghrelin secretion in humans and supports the hypothesis that insulin is a negative regulator of ghrelin secretion in the postprandial state. We did not find a negative relationship between endogenous somatostatin and ghrelin despite earlier reports that exogenously administered somatostatin analogues suppress plasma ghrelin. Finally, glucagon‐induced GH secretion is not mediated by an increase in plasma ghrelin.
Bone loss in males with ankylosing spondylitis: its relation to sex hormone levels
Authors: Aydin Teoman , Karacan İlhan , Demir Saliha Eroglu , Sahin Zerrin
Published: September 2005

Objective  Osteoporosis is a common complication of ankylosing spondylitis (AS). The aim of the present study was to assess the association of sex hormone levels with bone loss in males with AS.

Design  A cross‐sectional study.

Patients  The study group consisted of 58 male patients with primary AS. The mean age was 38·2 years (range 18–59 years).

Measurements  Bone mineral density (BMD) was measured in the left proximal femur. Serum FSH, LH, total testosterone (T), dehydroepiandrosterone sulfate (DHEAS), oestradiol (E2) and progesterone levels were measured.

Results  Bone loss was observed in 54·5% of cases at the femoral neck and in 52·3% of cases at the trochanter and total hip. Bone loss was found in 40 (69%) cases in at least one of these three regions. Serum DHEAS was low in 12 (30·8%) of the cases with bone loss, and one (5·9%) of those without (P = 0·043). The ratio of serum T/DHEAS was higher in those with bone loss (5·24 ± 3·70) than in those without (3·58 ± 3·16) (P = 0·026).

Conclusions  The results showed that bone loss might be related to low serum DHEAS levels in males with AS.
Electron backscattered diffraction characterization technique for analysis of a Ti2AlNb intermetallic alloy
Authors: WYNICK G. L. , BOEHLERT C. J.
Published: September 2005

This investigation was conducted to ascertain the benefits of electropolishing after mechanical polishing for electron backscattered diffraction of a Ti2AlNb intermetallic Ti−21Al−29Nb (at.%) alloy containing the orthorhombic (O) and body‐centered‐cubic (BCC) phases. Electropolishing was performed at −40 °C in 6% H2SO4 methanol solution. Atomic force microscopy was used to measure the surface topography in attempt to correlate nano‐scale surface roughness with electron backscatter diffraction pattern quality. The results suggest that mechanically polishing with colloidal silica (SiO2) or alumina followed by electropolishing is a sufficient surface preparatory technique for producing quality electron backscattered diffraction patterns for O + BCC microstructures. However, poor pattern quality results after mechanically polishing without electropolishing. High‐quality orientation maps for O‐dominated O + BCC microstructures were only possible through mechanical polishing followed by electropolishing. The data also suggest that surface roughness, on the order of 50 nm, has less effect on pattern quality than subsurface deformation. Overall, removing the near‐surface damage was more critical than reduction of topography.
Stage‐extension device for transmission light microscopes
Authors: KERN M. A.
Published: September 2005

For routine applications, more and more professional microscope users have removed the slide holders from their transmission light microscopes and frequently look over their histological specimens by moving them manually on the microscope stage. This method allows the operator to scan the specimen quickly under survey magnification and thus helps to save time. However, when using detail magnification, moving the sample by hand is simply not precise enough. This drawback becomes particularly evident with photo‐documentations or video demonstrations. Here I describe an innovative stage‐extension device that allows quick movement of the slide by hand as well as precise positioning of the specimen by using the micrometre fine adjustment of the coaxial stage‐drive mechanism.
Image‐based determination of chord lengths in air‐dried lungs
Authors: ROSENTHAL F. S. , BEGUM Z. A.
Published: September 2005

An image‐based method was developed in order to determine chord lengths in sections of dog and sheep lungs air‐dried at 25 cm H2O transpulmonary pressure. To facilitate image processing, optical contrast in the sections was optimized with respect to section thickness, stain type, stain concentration, staining temperature, staining time and clearing method. Digital processing of images used standard procedures, e.g. thresholding, dilation and thinning, as well as algorithms written to subtract background, delete spots and measure chord lengths. Correlation of image‐based vs. manual determination of mean chord length in 17 sections from a sheep lung, stained for optimal contrast yielded an R2 of 0.82 (P < 0.0001). For 95 sections from three dog lungs, stained with lower contrast, R2 was 0.65 (P < 0.0001). Weaker correlations were observed between image‐based and manual determinations of the standard deviation, the geometric standard deviation, and the 95th percentile of chord lengths (P < 0.05). The results show that image‐based stereology of inflated air‐dried lungs can provide valid measures of mean chord length and other statistics of chord length distribution.
The effects of sucrose on stability of human brain natriuretic peptide [hBNP (1–32)] and human parathyroid hormone [hPTH (1–34)]
Authors: Kamberi M. , Kim Y.J. , Jun B. , Riley C.M.
Published: September 2005

Abstract:  Although the effect of sucrose on the physical stability of proteins has been well documented, its impact on their chemical stability is largely unknown. The aim of this study was to investigate the potential effects of sucrose on the structural conformation of human brain natriuretic peptide [hBNP (1–32)] and the synthetic human parathyroid hormone [hPTH (1–34)], and link these effects to chemical degradation pathways of these peptides. The stability of hBNP (1–32) and hPTH (1–34) was studied at pH 5.5. Aggregation was monitored using size exclusion high‐performance liquid chromatography (SE‐HPLC), whereas oxidation and deamidation products were measured by reversed phase (RP) HPLC. Fourier transform infrared (FT‐IR) spectroscopy was used to study the peptides’ conformation. Sucrose retarded aggregation, deamidation, and oxidation of hBNP (1–32) and hPTH (1–34), with a maximum effect at relatively high concentrations (as much as 1 m). FT‐IR spectroscopy indicated that sucrose maintained the native conformation of hBNP (1–32) and induced small conformation changes in the hPTH (1–34) structure. Sucrose enhanced the stability of hBNP (1–32) and hPTH (1–34) in liquid formulations. The stabilizing effect of sucrose was due to a large extent to retardation of oxidation and deamidation of hBNP (1–32) and hPTH (1–34).
Sex Allocation in a Colobine Monkey
Authors: Ostner Julia , Borries Carola , Schülke Oliver , Koenig Andreas
Published: September 2005

In polygynous, sexual dimorphic species with higher variance in male reproductive success compared with females, females are expected to invest more heavily in sons than daughters within the constraints imposed by their physical condition (Science 1973; 179:90). Mothers in good condition, usually those of high rank, should produce more sons than females in poor condition or of low rank. We investigated sex allocation and sex‐biased maternal investment in a population of wild Hanuman langurs using rank and group size as approximations of female physical condition. Our results show that reproductive costs of sons were higher with both significantly longer interbirth intervals following male births and longer lactational periods for sons. Not in all groups did analyses of rank‐dependent sex allocation reveal the expected pattern of high‐ranking mothers producing more sons. However, sex ratio was significantly influenced by group size, with females from larger groups, i.e., in worse physical condition, producing a daughter‐biased sex ratio. In fact, only females of population‐wide superior physical condition can be expected to produce sons, because in Hanuman langurs males disperse and compete population‐wide. Thus, our results support the Trivers–Willard model and may explain the mixed evidence accruing from studies of single groups. We present a graphical model of how group size and dominance‐related differences in energy gain may influence sex allocation under different competitive regimes relative to overall resource availability. Tests of adaptive sex allocation models should consider whether reproductive competition of the preferred sex takes place primarily within a group or within the population.
Effects of Male Vocal Learning on Female Behavior in the Budgerigar, Melopsittacus undulatus
Authors: Hile Arla G. , Burley Nancy Tyler , Coopersmith Carol B. , Foster Valerie S. , Striedter Georg F.
Published: September 2005

Parrots are unusual among birds and animals in general in the extent of their ability to learn new vocalizations throughout life and irrespective of season. The budgerigar (Melopsittacus undulatus), a small parrot that is well suited for laboratory studies, has been the subject of numerous studies investigating the neurobiology of vocal learning. To date, few studies have focused on the function of vocal imitation by parrots. Previous work from our research group has shown that vocal imitation in budgerigars is sex‐biased, as males paired with females learn vocalizations from their new mates, but not vice versa. This bias led us to hypothesize that vocal learning has a reproductive function. To test this hypothesis, we conducted two experiments. In the first experiment, we tutored males so that they could produce a call similar to one shared by a group of experimental females. The experimental females were then presented with one of the tutored males and another, equally unfamiliar, male that had not been tutored. We found that the females spent a greater proportion of time in proximity of, and made more affiliative displays toward, the tutored males. In the second experiment, seven males received small bilateral brain lesions that disrupt vocal learning. These males and an equal number of control males were then released into an aviary containing females and reproductive resources. We found that lesioned and control males were equally successful in obtaining social mates, but females mated to lesioned males were more likely to engage in extra‐pair activities. These experiments indicate that a male's ability to imitate a female's call can influence the sexual behavior of the female even though lack of imitation ability does not appear to influence social pairing. We hypothesize that mate choice in budgerigars has multiple stages. Upon meeting a strange male, a female quickly assesses its ability for social acquisition of calls by the presence or absence of a call type similar to its own in its repertoire. As courtship proceeds into pair formation, the female assesses the ability of male to learn more directly by the extent of the male's perfection of imitation.
Status and Reproduction in Humans: New Evidence for the Validity of Evolutionary Explanations on Basis of a University Sample
Authors: Fieder Martin , Huber Susanne , Bookstein Fred L. , Iber Karoline , Schäfer Katrin , Winckler Georg , Wallner Bernard
Published: September 2005

A strong positive relationship between reproductive success (offspring count) and status (position in the institutional hierarchy) is demonstrated in a contemporary sample of male university employees (n = 2693). Male academics in leading positions have more children than do other male employees. In female university employees (n = 2073), a negative relationship between status and reproductive success was found, but only if childless women were included in the analysis. Although a positive relationship between male status and offspring count has been predicted by evolutionary theory and was found in animal species and ‘traditional’ human societies, in modern societies most of the studies found no or even a negative relationship between status and reproductive success in males. We suggest that status may be a more important dimension for particular subsamples of modern society than for samples representing entire societies, so that associations might actually differ among subsamples. We suggest that analyses on a small and rather uniform level using modern large‐scale hierarchical organizations (such as universities) are candidates for the investigation of appropriate ‘society subsets’. Our results may stress the importance of evolutionary predictions and may be of relevance for theoretical and empirical considerations at the levels of economics and administration.
Up‐regulation of lysosomal cathepsin L and autophagy during neuronal death induced by reduced serum and potassium
Authors: Kaasik Allen , Rikk Tiina , Piirsoo Andres , Zharkovsky Tamara , Zharkovsky Alexander
Published: September 2005

Serum and potassium deprivation‐induced neuronal death on the primary culture of rat cerebellar granule neurons is being widely used as an in vitro model of neurodegeneration and neuronal apoptosis. In our experiments, serum and potassium deprivation for 12 h induced neuronal death in ≈ 20% of cerebellar granule neurons as demonstrated by Trypan Blue assay. Neuronal death was accompanied by a transient increase in the intralysosomal cathepsin L activity, which preceded neuronal death. During this time, the lysosomal membrane integrity remained preserved and no leakage of cathepsin L into the cytosol was seen. Ultrastructural analysis revealed the appearance of multiple vacuoles and autophagosomes in the cytoplasmatic compartment of serum‐ and potassium‐deprived granule neurons. Addition of selective cathepsin L inhibitors or of the autophagy inhibitor 3‐methyladenine provided partial protection against serum and potassium deprivation‐induced death. Our data also show that combining cathepsin L inhibitors and caspase‐3 inhibitors leads to a synergistic neuroprotective effect against serum and potassium deprivation. The results of the current study suggest that activation of the autophagosomal–lysosomal compartment plays an important role in neuronal death induced by serum and potassium deprivation in cultured cerebellar granule cells.
Temperature cycles drive Drosophila circadian oscillation in constant light that otherwise induces behavioural arrhythmicity
Authors: Yoshii Taishi , Heshiki Yoshihiro , Ibuki‐Ishibashi Tadashi , Matsumoto Akira , Tanimura Teiichi , Tomioka Kenji
Published: September 2005

The fruit fly, Drosophila melanogaster, shows a clear circadian locomotor rhythm in light cycles and constant darkness. Although the rhythm disappears in constant light, we found that temperature cycles drive the circadian rhythm both in locomotor activity and molecular abundance of PERIOD (PER) and TIMELESS (TIM). The thermoperiodically induced locomotor rhythm entailed an anticipatory activity at the late thermophase, which required several transient cycles to establish a steady‐state entrainment, suggesting that the rhythm is endogenous and driven by a circadian clock. Western blot analysis revealed that PER and TIM increased during the cryophase, peaking at the middle to late cryophase. PER was also cyclically expressed under the temperature cycle in the known per‐expressing neurons, i.e. so‐called lateral (LNs) and dorsal neurons (DNs), and two pairs of cells (LPNs) that were located in the lateral posterior protocerebrum. It is thus suggested that the temperature cycle induces the cycling of PER and TIM either by blocking somewhere in the photic entrainment pathway during the cryophase or temporally activating their translation to sufficient protein levels to drive a circadian oscillation. In flies lacking pigment‐dispersing factor (PDF) or PDF‐expressing cells, the anticipatory activity was relatively dispersed. disco2 mutant flies lacking the lateral neurons still showed an anticipatory activity, but with dispersed activity. These behavioural results suggest that not only LNs but also DNs and LPNs can, at least, partially participate in regulating the thermoperiodically induced rhythm.
Expression of the mu‐opioid receptor is induced in dentate gyrus granule cells after focal cerebrocortical ischaemia and stimulation of entorhinal afferents
Authors: Stumm Ralf , Rüthrich Heinz , Schulz Stefan , Zhou Chun , Hollt Volker
Published: September 2005

Focal ischaemia in the cerebral cortex affects the inducibility of long‐term potentiation (LTP) in the hippocampus. This impairment of hippocampal function may result from excessive activation of cortico‐hippocampal afferents and subsequent perturbation of hippocampal LTP‐relevant transmitter systems, which include opioids. Here, we tested if permanent focal ischaemia and electrical afferent stimulation influence the expression of the mu‐opioid receptor (MOR) in the rat hippocampus. In the applied ischaemia model, the entire ipsilateral cortical hemisphere and hippocampus experienced sustained excitation as indicated by a long‐lasting increase in the expression of arg 3.1/arc (ARG) mRNA, a marker for neuronal activity. Expression of MOR mRNA and protein was strongly increased in granule cells, which contain very low MOR levels under normal conditions, but not in γ‐aminobutyric acid (GABA)ergic neurons, which express the MOR constitutively. In the molecular layer, which contains the dendrites of granule cells, focal ischaemia caused a redistribution of MOR‐like immunoreactivity. In contrast to the dentate gyrus, MOR expression was unaltered in the hippocampus proper and in non‐infarcted cortical areas. Repetitive high‐frequency stimulation of cortico‐hippocampal perforant path afferents induced strong MOR mRNA expression throughout the granular layer. However, weak tetanization sufficient to induce LTP and ARG expression did not influence MOR mRNA levels. Taken together, we provide direct evidence for the induction of MOR expression in granule cells experiencing sustained excitation by cortical afferents. In activated, MOR‐expressing granule cells, inhibitory opioids may counter‐regulate glutamatergic excitation by the perforant path.
Apoptotic cell death progression after photothrombotic focal cerebral ischaemia: effects of the lipophilic iron chelator 2,2′‐dipyridyl
Authors: Van Hoecke Michaël , Prigent‐Tessier Anne , Bertrand Nathalie , Prevotat Laurent , Marie Christine , Beley Alain
Published: September 2005

Two different forms of cell death have been distinguished morphologically following cerebral ischaemia: necrotic and apoptotic cell death. The aim of this study was to investigate the contribution of apoptosis to ischaemic damage by carefully depicting the temporal and spatial neuronal death following focal ischaemia. For this purpose, rats were subjected to chemical photothrombosis, and histological and biochemical analyses were performed over a period of 24 h after the onset of ischaemia. In addition, the effects of the lipophilic antioxidant iron chelator 2,2′‐dipyridyl (DP) were evaluated 24 h after photothrombosis when the lesion volume was maximal. Our results showed two separate waves of neuronal death. In the first wave, shrunken dark neurons were massively present as early as 2 h after photothrombosis in the infarct core. From this initial neuronal abnormal population, progressive and time‐dependent changes of both necrotic and apoptotic cell death were observed, leading to ghost neurons and apoptotic bodies after 24 h. The extension of the lesion coincided with a second wave of cell death. Massive and rapid neuronal loss occurred at the infarct border, which appeared as a sharply demarcated pale region. Procaspase and poly(ADP‐ribose) polymerase‐1 (PARP‐1) cleavages were also detected in the infarct core and surrounding damaged tissue. DP treatment markedly blocked the enlargement of the lesion, the infarct border being rescued from infarction. Furthermore, a large decrease of apoptotic bodies was associated with a significant drop of caspase and PARP‐1 cleavages, suggesting that the protective effect of DP closely correlates with limitation of apoptosis expansion.
Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats
Authors: Cuenca Nicolás , Pinilla Isabel , Sauvé Yves , Lund Raymond
Published: September 2005

The Royal College of Surgeons (RCS) rat has a retinal pigment epithelial cell defect that causes progressive loss of photoreceptors. Although it is extensively used in retinal degeneration and repair studies, how photoreceptor degeneration affects retinal circuitry has not been fully explored. This study examined the changes in synaptic connectivity between photoreceptors and their target cells using immunocytochemistry and correlated these changes with retinal function using the electroretinogram (ERG). Immunostaining with bassoon and synaptophysin (as presynaptic markers) and metabotropic glutamate receptor (mGluR6, a postsynaptic marker for ON‐bipolar dendrites) was already impaired at postnatal day (P) 21 and progressively lost with infrequent pairing of presynaptic and postsynaptic elements at P60. By P90 to P120, staining became increasingly patchy and was eventually restricted to sparsely and irregularly distributed foci in which the normal pairing of presynaptic and postsynaptic markers was lost. ERG results showed that mixed scotopic a‐waves and b‐waves were already reduced by P21 but not oscillatory potentials. While cone‐driven responses (photopic b‐wave) reached normal levels at P30, they were impaired by P60 but could still be recorded at P120, although with reduced amplitude; rod responses never reached normal amplitudes. Thus, only cone‐driven activity attained normal levels, but declined rapidly thereafter. In conclusion, the synaptic markers associated with photoreceptors and processes of bipolar and horizontal cells show abnormalities prior to significant photoreceptor loss. These changes are paralleled with the deterioration of specific aspects of ERG responsiveness with age. Besides providing information on the effects of photoreceptor dysfunction and loss on connection patterns in the retina, the work addresses the more general issue of how disorder of input neurons affects downstream circuitry.
Functional and molecular development of striatal fast‐spiking GABAergic interneurons and their cortical inputs
Authors: Plotkin Joshua L. , Wu Nanping , Chesselet Marie‐Françoise , Levine Michael S.
Published: September 2005

Despite their small number, fast‐spiking (FS) GABAergic interneurons play a critical role in controlling striatal output by mediating cortical feed‐forward inhibition of striatal medium‐sized spiny (MS) projection neurons. We have examined the functional development of FS interneurons and their cortical inputs, and the expression of three of their molecular markers, in the dorsolateral rat striatum between postnatal days (P)12–14 and 19–23, the time of major corticostriatal synaptogenesis. FS interneurons were visualized with infrared differential interference contrast (IR‐DIC) optics and examined with current‐clamp recording in the presence of the GABAA receptor antagonist bicuculline methiodide. FS interneurons displayed action potentials at relatively high frequencies in response to depolarizing current pulses by P12, but developmental changes occurred in action potential and afterhyperpolarization duration and amplitude and input resistance between P12–14 and P19–23, as well as an increase in maximum firing frequency in response to depolarizing current pulses. Maturation in electrophysiological properties was paralleled by increases in Kv3.1 and parvalbumin mRNA expression, while GAD‐67 mRNA levels remained constant. Furthermore, FS interneurons in the younger age group responded to stimulation of cortical afferents with excitatory postsynaptic potentials (EPSPs) of higher amplitudes and received significantly more spontaneous depolarizing inputs than did MS neurons. Thus, FS interneurons are under frequent and continuous cortical influence by the end of the 2nd postnatal week, a time when corticostriatal synapses are sparse, suggesting that they may provide a major inhibitory influence in the striatum during the period of intense developmental maturation.
Synapse independence breaks down during highly synchronous network activity in the rat hippocampus
Authors: Biró Ágota A. , Nusser Zoltan
Published: September 2005

The discharge pattern of hippocampal pyramidal cells (PC) varies depending on the behaviour of the animal and on the accompanying network states. During theta activity, PCs fire asynchronously at low rates whereas during sharp waves PCs increase their firing frequency and many cells fire synchronously. In the present study, we addressed how the presynaptic activity of CA1 PCs influences the precise operation of their output synapses. Asynchronous presynaptic discharge was mimicked by activating only a single PC during paired recordings, whereas the highly synchronous presynaptic firing was emulated by extracellularly stimulating the axons of ≈ 70 PCs in acute hippocampal slices. By using low‐ and high‐affinity glutamate receptor competitive antagonists to monitor the synaptic glutamate concentration transient, we show that the synaptic transmitter concentration varies depending on the release probability (Pr) when many fibres are synchronously activated. Our kinetic analysis revealed that an ≈ 5‐fold increase in Pr from the beginning to the end of an action potential train resulted in a slowing down of the decay of evoked EPSCs, suggesting neurotransmitter spillover between neighbouring synapses. In agreement with this prediction, the slowing of the decay was reversed by the application of the low‐affinity antagonist γ‐D‐glutamyl‐glycine. In contrast, altering Pr had no effect on the kinetics of unitary EPSCs. Our data demonstrate that synapse independence breaks down during synchronous presynaptic activity, but the point‐to‐point communication is preserved when PCs fire asynchronously.
Ryanodine receptors and BK channels act as a presynaptic depressor of neurotransmission in cochlear inner hair cells
Authors: Beurg Maryline , Hafidi Aziz , Skinner Liam J. , Ruel Jérome , Nouvian Régis , Henaff Morgana , Puel Jean‐Luc , Aran Jean‐Marie , Dulon Didier
Published: September 2005

Ryanodine receptors (RyRs) are known to contribute to the regulation of free cytosolic calcium concentration. This family of intracellular calcium channels plays a significant role in calcium‐induced‐calcium‐release (CICR), and have been implicated in calcium‐dependent processes requiring exquisite spatio‐temporal regulation. In order to characterize the importance of these intracellular calcium channels in cochlear physiology, we perfused the guinea pig cochlea with antagonistic concentrations of ryanodine. The distortion products of the cochlear microphonic and the compound action potential of the auditory nerve were reversibly inhibited by ryanodine (IC50 = 27.3 µm, Hill coefficient = 1.9), indicating an action at the cochlear amplifier. Single auditory nerve fibre recordings showed that ryanodine slightly increased spontaneous firing rates by 22%, suggesting an excitatory effect of ryanodine. This paradoxical effect could be explained by an inhibitory action of ryanodine on presynaptic BK channels of inner hair cells (IHC). Indeed, perfusing iberiotoxin also increased the spontaneous firing activity of the auditory nerve fibres. Furthermore, whole‐cell patch‐clamp recordings demonstrated that ryanodine inhibits BK currents at the IHC level. Conversely, immunohistochemistry demonstrated a strong expression of RyR in IHCs and, more particularly, below the cuticular plate where membranous BK channels are highly expressed. Overall, the study demonstrated a key role for RyR and CICR in signal transduction at the IHCs. We therefore propose that coupled RyR–BK channels act to suppress the fast neurotransmission in IHCs.
Photoperiodic regulation of annual testicular events in the Indian major carp Catla catla
Authors: Bhattacharyya S. , Dey R. , Maitra S. K.
Published: September 2005

The importance of photoperiods in the regulation of annual testicular events in the carp Catla catla was evaluated by subjecting them to either long (16 h light : 8 h dark) or short (8 h light : 16 h dark) photoperiods for 30 days during the preparatory, prespawning, spawning and postspawning phases of an annual gonadal cycle. In each reproductive phase, testicular responsiveness to subjected photoperiods was determined by comparing the gonadal status in corresponding groups of control or natural photoperiodic fish. The values of testicular weight, gametogenic index, as well as testicular activity of two steroidogenic enzymes (Δ53β‐, and 17β‐hydroxysteroid dehydrogenase), and the serum titre of testosterone were considered as the indices of functional status of the testis in the fish concerned. During the prespawning phase, exposure of fish to a daily long photoperiod schedule resulted in precocious maturation of testis, while retardation of testicular growth was noted under the influences of short photoperiod. However, none of the employed photo‐schedules could influence the gametogenic and steroidogenic functions of the testis in the remaining part of the gonadal cycle. Collectively, the present study provides evidence for the first time that in the case of a commercially important carp, Catla catla, artificial, long photoperiods may be used for advanced testicular maturation, while reductions in maturation‐associated growth and deterioration in flesh quality may be avoided by submitting the fish to shorter day lengths during the prespawning phase of the reproductive cycle.
Pretarsal structures in Reduviidae (Heteroptera, Ins ecta)
Authors: Weirauch Christiane
Published: September 2005

A survey of pretarsal structures in Reduviidae of 22 higher‐level taxa and several outgroup representatives is conducted using scanning electron microscopy (SEM) and light microscopy. Based on histology and SEM, pretarsal structures are described in detail forRhodnius prolixus. Structures of the distal tarsomer, which appear to be functionally correlated with the pretarsus, are documented for the first time in Heteroptera. These comprise lateral oval sclerites, two campaniform sensilla and two marginal setae, observed in Reduviidae and other heteropteran taxa. The presence of a peg‐like dorsomedian sensillum medially between the claws in Reduviidae and Nabidae is demonstrated. As a result of its structure and position, homology of this sensillum with the ‘dorsal arolium’ in other heteropteran groups is proposed. Within Reduviidae, the transformation of the peg‐like dorsomedian sensillum to a campaniform sensillum, as seen in most representatives of the harpactoroid complex, is hypothesized. The first record of parempodia other than setiform within Reduviidae is noted in nymphs of Harpactorinae, which may possess lamellate parempodia. Several characters that are possibly useful for clarifying relationships among the harpactoroid groups are described and discussed. The pretarsal structures, including the unguitractor plate and the tarsal marginal setae among reduviid groups are discussed in a phylogenetic context.
Comparative morphology of the first instar of three species of Metopia Meigen (Diptera: Sarcophagidae, Miltogramminae)
Authors: Szpila K. , Pape T.
Published: September 2005

The first instar larva is described for three species of the kleptoparasitic miltogrammine genus Metopia Meigen: M. campestris (Fallén), M. argentata Macquart and M. argyrocephala (Meigen). Using a combination of light microscopy and scanning electron microscopy, the morphology of the cephaloskeleton as well as the general external morphology are extensively documented, and the phylogenetic implications are discussed. Like other species of Miltogramminae, the first instar of species of Metopia possesses a strong labrum and well‐developed mouth‐hooks. Some other features found in Metopia spp. are rare in the Miltogramminae, such as a serrated ventral surface of the tip of the mouth‐hook and the lack of a posterior spiracular cavity. A few larval features apparently unique for species of Metopia have so far been documented: base of mouth‐hook with a lateral arm‐like extension and abdominal segments with transverse furrow ventrally. The body is equipped with longitudinal cuticular ridges on all segments, which may be a subfamily ground‐plan autapomorphy. Marked morphological and behavioural differences are documented between the first instar of M. argentata and that of M. argyrocephala, the adult females of which are otherwise difficult to separate.
Ontogenetic variations in characters of Euchone analis (Krøyer, 1856) (Polychaeta, Sabellidae, Sabellinae) from Spitsbergen, and new assignments of Oriopsis ingelorae Plate, 1995 and O. liefdefjordensis Plate, 1995
Authors: Bick Andreas , Randel Nadine
Published: September 2005

Euchone analis, the type species of its genus, was collected in high densities and in different size classes from Kongsfjorden, west Spitsbergen. This material has provided the basis for an investigation of the size dependence of characters. Almost all characters used in diagnoses were highly variable, especially the number of abdominal chaetigers forming the anal depression and the shape of the depression. The only relatively constant features are the number of chaetigers anterior to the anal depression and the branchial crown‐to‐body length ratio. A branchial skeleton extension of the radiolar appendages of the dorsal lips was found for the first time within Euchone, and this character has been added to the diagnosis of Euchone. Oriopsis liefdefjordensis and small specimens of E. analis agree in all characters, and O. liefdefjordensis is proposed to be a junior synonym of E. analis. Characters found in O. ingelorae are in accordance with those described for Chone, and we propose assigning O. ingelorae to this genus. The significance of ontogenetic character variations in the Sabellidae is discussed.
Emerging evidence for a similar role of glutamate receptors in the nervous and immune systems
Authors: Boldyrev Alexander A. , Carpenter David O. , Johnson Peter
Published: September 2005

The role of glutamate receptors in synaptic transmission and excitotoxicity in the nervous system is well established. Recent evidence has emerged that glutamatergic mechanisms also exist in a wide variety of non‐neuronal cells. In the case of thymocytes and lymphocytes, several types of glutamate receptor are expressed which can induce functional changes. This review focuses on the cellular function of NMDA‐activated ionotropic and groups I and III metabotropic glutamate receptors in lymphocytes. Levels of exogenous and endogenous circulatory agonists and antagonists for lymphocyte glutamate receptors, notably homocysteine metabolites, are markedly increased in certain disease states and may be involved in disorders of the immune system. In addition to glutamate and aspartate, these compounds are active at glutamate receptors and increase the excitotoxic effects of glutamate in both neurons and lymphocytes. Increased levels of compounds acting at glutamate receptors may be risk factors for organ damage, for example in both heart and kidney disease. We conclude that glutamate is involved in signaling in immunocompetent cells and that the expression of both ionotropic and metabotropic glutamate receptors may have regulatory functions in immunocompetent cells, as well as in the nervous system. In addition, glutamate may serve as a signaling agent between the immune and nervous systems.
Role of AP‐1 in ethanol‐induced N‐methyl‐d‐aspartate receptor 2B subunit gene up‐regulation in mouse cortical neurons
Authors: Qiang Mei , Ticku Maharaj K.
Published: September 2005

Activator protein 1 (AP‐1) has been reported to regulate the gene expression in a wide variety of cellular processes in response to stimuli. In this study, we investigated the DNA‐protein binding activities and promoter activity in the N‐methyl‐d‐aspartate R2B (NR2B) gene AP‐1 site in normal and ethanol‐treated cultured neurons. The identity of the AP‐1 site as the functional binding factor is suggested by the specific binding of nuclear extract derived from cultured cortical neurons to the labeled probes and the specific antibody‐induced supershift. Mutations in the core sequence resulted in a significantly reduced promoter activity and the ability to compete for the binding. Moreover, treatment of the cultured neuron with 75 mm ethanol for 5 days caused a significant increase in the AP‐1 binding activity and promoter activity. The AP‐1 DNA‐binding complex in control and ethanol‐treated nuclear extract was composed of c‐Fos, FosB, c‐Jun, JunD, and phosphorylated CREB (p‐CREB). Western blot analysis showed that p‐CREB and FosB significantly increased, whereas c‐Jun decreased. The DNA affinity precipitation assay indicated that FosB, p‐CREB, and c‐Jun increased in the AP‐1 complex following ethanol treatment. These results suggest that AP‐1 is an active regulator of the NR2B transcription and ethanol‐induced changes may result at multiple levels in the regulation including AP‐1 proteins expression, CREB phosphorylation and perhaps reorganization of dimmers.
How to measure non‐consistency of medical practices with available evidence in therapeutics: a methodological framework
Authors: Boissel Jean‐Pierre , Nony Patrice , Amsallem Emmanuel , Mercier Catherine , Estève Jacques , Cucherat Michel
Published: September 2005

Since the early 1980s many studies showed a gap between available evidence and medical practice. They were designed to assess the real impact of randomized clinical trials on the practice of medicine. Their results substantiated a knowledge translation problem. However, they were qualitative findings, i.e. a gap exists or not, although the problem is quantitative (how large is the gap?) and has several components that should be documented according to the objective of the study. In this article, we explored the components and the various contexts in which the measure of the distance between practice and knowledge is considered. All these features should be taken into account for a more accurate and relevant assessment of the distance.
Population pharmacokinetics of ketanserin in pre‐eclamptic patients and its association with antihypertensive response
Authors: Hanff Lidwien M. , Visser Wil , Steegers Erik A.P. , Vulto Arnold G.
Published: September 2005

Ketanserin is an antihypertensive drug that is increasingly being used parenterally in the treatment of pre‐eclampsia. Because of lack of efficacy in a substantial part of our pre‐eclamptic patients, we determined the plasma concentrations of ketanserin in 51 pre‐eclamptic patients. Population pharmacokinetic parameters were assessed using the iterative two‐stage Bayesian population procedure. The influence of individual pharmacokinetic parameters on antihypertensive response, expressed as the attainment of a diastolic blood pressure ≤90 mmHg using ketanserin treatment, was analysed. Almost all plasma concentrations of ketanserin were in or above the therapeutic range. The individual pharmacokinetics of ketanserin in pre‐eclamptic patients showed an accurate fit using a three‐compartment model. The pharmacokinetic parameters in our pre‐eclamptic population were a metabolic clearance (Clm) of 37.9 ± 10.86 L/h and volume of distribution (V1) of 0.544 ± 0.188 L/kg, which is comparable with data from healthy volunteers. Despite a considerable inter‐individual variation, no correlation was found between differences in pharmacokinetic parameters and antihypertensive response. We conclude that therapeutic plasma levels can be obtained in pre‐eclamptic patients with a fixed dosage schedule of ketanserin and differences in antihypertensive responses within a pre‐eclamptic population cannot be attributed to pharmacokinetic differences.
Modulation of spontaneous alternation performance of mice treated with thioperamide and tacrine in a cross maze task
Authors: Vohora Divya , Pal Shanthi N. , Pillai K.K.
Published: September 2005

A combination of sub‐effective doses of thioperamide (7.5 mg/kg, i.p.) and tacrine (0.5 mg/kg, i.p.) enhanced performance in a spatial memory task in mice. This was shown by a significant increase in their spontaneous alternation scores in a cross maze test.
Effect ofN‐benzoyl‐d‐phenylalanine on lipid profile in liver of neonatal streptozotocin diabetic rats
Authors: Pari Leelavinothan , Ashokkumar Natarajan
Published: September 2005

The effect ofN‐benzoyl‐d‐phenylalanine (NBDP) and metformin combination treatment on liver lipids and lipid peroxidation markers was studied in neonatal streptozotocin (nSTZ) diabetic rats. Oral administration of NBDP (50, 100 and 200 mg/kg body weight) and metformin (500 mg/kg body weight) for 6 weeks significantly reduced the elevated blood glucose, liver cholesterol, triglycerides, free fatty acids and phospholipids. The combination treatment also caused a significant decrease in hepatic hydroxymethyl glutaryl‐coenzyme A reductase, Thiobarbituric Acid Reactive Substances (TBARS) and significant increase in reduced glutathione levels. The results show that NBDP and metformin improve the hepatic lipid profile and antioxidant status in nSTZ diabetic rats. Combination treatment was more effective than either drug alone.
Characterization of human cytochrome P450 isoenzymes involved in the metabolism of vinorelbine
Authors: Beulz‐Riché Dominique , Grudé Pascale , Puozzo Christian , Sautel François , Filaquier Christian , Riché Christian , Ratanasavanh Damrong
Published: September 2005

Vinorelbine (VRL) (IV Navelbine®) is a semi‐synthetic vinca alkaloid, used in therapeutics for the treatment of non‐small‐cell lung cancer and advanced breast cancer. The aim of this study was to characterize the cytochrome P450 (CYP) isoenzymes involved in VRL metabolism. VRL was incubated at 1.28 × 10−5 m for 90 min with human hepatic microsomes prepared from 14 donors (one woman and 13 men aged from 27 to 76 years old) and characterized for CYP1A2, CYP2D6, CYP2E1 and CYP3A4 activities. A four‐combined‐approach study was performed, including correlation between CYP activities and VRL metabolism among the 14 batches of microsomes, inhibition of VRL biotransformation by isoform‐selective substrates and by specific inhibitory antibodies, and incubation with supersomes®. Analysis of unchanged VRL and its metabolites was performed using an HPLC method coupled with both radioactive and UV detections. No correlation between CYP1A2 or CYP2E1 and VRL metabolism was observed in the 14 batches of microsomes used. A correlation was shown between VRL metabolism and CYP3A4 activity as determined with the dextromethorphan N‐demethylase and nifedipine oxidase activities (r2 = 0.80 and 0.59, respectively). These results were strengthened by a correlation between the metabolism extent of VRL and CYP3A4 protein content determined by immunoblotting (r2 = 0.75). Furthermore, VRL biotransformation was inhibited by troleandomycine, the CYP3A4‐specific inhibitor substrate (80% of inhibition) and by anti‐CYP3A antibodies (36% of inhibition). On the contrary, a low correlation with CYP2D6 activity as determined by dextrometorphan O‐demethylation (r2 = 0.31) was established. CYP2D6 supersomes® did not metabolize the drug whereas 63.4% of VRL were metabolized by microsomes overexpressing CYP3A4 isoform. These data indicated that CYP3A4 is the main enzyme involved in the hepatic metabolism of VRL in human, whereas CYP2D6 is not involved.
Public Service Broadcasting*
Authors: Armstrong Mark
Published: September 2005

This essay discusses the merits of public intervention in the provision of television broadcasting services. I argue that intervention was justified in the past, when there were just a few channels and when advertising was the sole source of commercial funds. However, the advent of subscription television overcomes many of the market failures that once existed. Moreover, asymmetric treatment of broadcasters acts to distort the incentives of commercial broadcasters. Finally, viewers have an increasing ability to avoid unappealing, but perhaps socially desirable, content, which further weakens the case for public intervention in the market.
The New Deal for Young People Five Years On*
Authors: De Giorgi Giacomo
Published: September 2005

The New Deal for Young People is the major welfare‐to‐work programme in the UK. It is a mandatory multistage policy targeted at 18‐ to 24‐year‐old unemployed people. This paper investigates the long‐term effectiveness of the programme in terms of enhancing the (re‐)employment probability of participating men. It exploits the eligibility rule to identify a suitable counterfactual relying upon a simple regression discontinuity design. The combination of job‐search assistance, training, wage subsidies and job experience enhances employability by about 4.6 per cent and this effect lasts over different cohorts.