bluuebunny/crossref_metadata_2025 huggingface dataset:
Short‐term subjective efficacy of doxazosin in predicting probability of prostatectomy in the management of benign prostatic hyperplasia in patients with severe symptoms
Authors: CAM KAMIL , AKMAN YAVUZ , KAYIKCI ALI , SENEL FERDA , EROL ALI
Published: October 2003

Background:  The severity of symptoms still constitutes the major indication for transurethral prostatectomy, despite the extensive utilization of medical treatments. The aim of the study presented here was to investigate the impact of doxazosin on symptoms in relation to the probability of consequent surgery in severely symptomatic patients.

Methods:  Patients with an International Prostate Symptom Score (IPSS) between 18 and 35 were included in the study. The patients received 4 mg/day doxazosin, and subjective efficacy was assessed by IPSS at the first and third months. In addition, the patients were classified at the third month according to a single question regarding satisfaction with medical treatment in terms of symptom relief as ‘ineffective, no change, and effective’.

Results:  A total of 178 patients constituted the study group. Mean total symptom scores were 24, 19 and 17 at baseline, first and third months, respectively (P < 0.05). According to results of the questionnaire, 23% of the patients claimed the treatment was ineffective, and subsequently, the majority of this group (93%) underwent prostatectomy in a year. In addition, 33% of the patients reported no change in their symptoms, while 44% reported that the medication was effective. However, after 1 year, 59% and 15% of these cases underwent surgical treatment, respectively. The probability of surgery in the ‘ineffective’ group was significantly higher compared to the remaining groups (P < 0.05).

Conclusion:  The majority of patients with severe symptoms who were not satisfied with the medication at the 3rd month underwent surgery. This observation may provide a predictor for subsequent probability of prostatectomy. Therefore, reassessment of patients would be a cost‐effective approach for the treatment of BPH in severely symptomatic patients.
Generation of retinal ganglion cells is modulated by caspase‐dependent programmed cell death
Authors: Mayordomo Raquel , Valenciano Ana I. , De La Rosa Enrique J. , Hallböök Finn
Published: October 2003

Programmed cell death occurs during both early and late neural development. The mechanisms for the regulation and execution of the early cell death as well as its developmental role are still not fully understood. In this work we have studied the early programmed cell death in the retinal neuroepithelium. Apoptotic cells were selectively located around the optic nerve head in the retinal neuroepithelium of 2‐ to 6‐day‐old chick embryos. TUNEL‐positive cells and cells which were immunostained for activated caspase‐3 showed overlapping distributions suggesting that caspase‐3 is involved in the early retinal cell death. Caspase‐3 involvement in early retinal cell death was also demonstrated by in vivo treatment with caspase inhibitors z‐DEVD‐fmk and Boc‐D‐fmk. After 6 h of treatment, the number of TUNEL‐positive cells was reduced by 50%. Sustained treatments (20 h) resulted in a slight widening in the central part of the neural retina but the retinal ganglion cell axons maintained their organization and navigation towards the optic fissure. The most prominent result after inhibition of cell death was an increase in the number of retinal ganglion cells which also produced an enlargement of the ganglion cell layer and an increased number of ganglion cell axons. In conclusion, our results show that caspase‐dependent programmed cell death occurs in the embryonic chick retina and that it plays a role to modulate the generation of retinal ganglion cells.
Complementary distribution of type 1 cannabinoid receptors and vesicular glutamate transporter 3 in basal forebrain suggests input‐specific retrograde signalling by cholinergic neurons
Authors: Harkany Tibor , Härtig Wolfgang , Berghuis Paul , Dobszay Marton B. , Zilberter Yuri , Edwards Robert H. , Mackie Ken , Ernfors Patrik
Published: October 2003

Basal forebrain cholinergic neurons project to diverse cortical and hippocampal areas and receive reciprocal projections therefrom. Maintenance of a fine‐tuned synaptic communication between pre‐ and postsynaptic cells in neuronal circuitries also requires feedback mechanisms to control the probability of neurotransmitter release from the presynaptic terminal. Release of endocannabinoids or glutamate from a postsynaptic neuron has been identified as a means of retrograde synaptic signalling. Presynaptic action of endocannabinoids is largely mediated by type 1 cannabinoid (CB1) receptors, while fatty‐acid amide hydrolase (FAAH) is involved in inactivating some endocannabinoids postsynaptically. Alternatively, vesicular glutamate transporter 3 (VGLUT3) controls release of glutamate from postsynaptic cells. Here, we studied the distribution of CB1 receptors, FAAH and VGLUT3 in cholinergic basal forebrain nuclei of mouse and rat. Cholinergic neurons were devoid of CB1 receptor immunoreactivity. A fine CB1 receptor‐immunoreactive (ir) fibre meshwork was present in medial septum, diagonal bands and nucleus basalis. In contrast, the ventral pallidum and substantia innominata received dense CB1 receptor‐ir innervation and cholinergic neurons received CB1 receptor‐ir presumed synaptic contacts. Consistent with CB1 receptor distribution, FAAH‐ir somata were abundant in basal forebrain and appeared in contact with CB1 receptor‐containing terminals. Virtually all cholinergic neurons were immunoreactive for FAAH. A significant proportion of cholinergic cells exhibited VGLUT3 immunoreactivity in medial septum, diagonal bands and nucleus basalis, and were in close apposition to VGLUT3‐ir terminals. VGLUT3 immunoreactivity was largely absent in ventral pallidum and substantia innominata. We propose that specific subsets of cholinergic neurons may utilize endocannabinoids or glutamate for retrograde control of the efficacy of input synapses, and the mutually exclusive complementary distribution pattern of CB1 receptor‐ir and VGLUT3‐ir fibres in basal forebrain suggests segregated input‐specific signalling mechanisms by cholinergic neurons.
Facilitation of conditioned taste aversion learning by systemic amphetamine: role of nucleus accumbens shell dopamine D1 receptors
Authors: Fenu Sandro , Di Chiara Gaetano
Published: October 2003

The role of dopamine (DA) in associative learning was studied in a conditioned taste aversion (CTA) paradigm with sucrose as the conditioned stimulus (CS) and intraperitoneal lithium chloride as the unconditioned stimulus (US). Drinking on trial of a 15% sucrose solution followed 1 h later by lithium chloride (20 or 40 mg/kg i.p.) resulted in mild CTA, as shown by reduction of drinking of the sucrose solution 24 h later. Amphetamine sulphate (0.125, 0.25, 0.50 and 1.0 mg/kg s.c.), administered on trial 5 min after sucrose drinking, facilitated CTA with maximal effects at 0.25 mg/kg s.c. Amphetamine given in the absence of lithium or 45 min after sucrose did not affect sucrose intake. The DA D1 receptor antagonist SCH 39166, administered before amphetamine either systemically (0.0125 mg/kg s.c.) or in the nucleus accumbens shell (NAc; 0.025 µg/µL on each side) prevented the facilitation of CTA induced by amphetamine. It is concluded that amphetamine facilitates CTA learning by strengthening the consolidation of gustatory short‐term memory via D1 receptors of the NAc shell.
The rat nucleus accumbens is involved in guiding of instrumental responses by stimuli predicting reward magnitude
Authors: Giertler Christian , Bohn Ines , Hauber Wolfgang
Published: October 2003

The present study examined the involvement of N‐methyl‐d‐aspartate (NMDA), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolpropionate/kainate (AMPA/KA) and dopamine receptors in the nucleus accumbens (ACB) in influencing reaction times of instrumental responses by the expectancy of reward. A simple reaction time task demanding conditioned lever release was used in which the upcoming reward magnitude was signalled in advance by discriminative cues. After training, in control rats with vehicle infusions (0.5 µL) into the ACB, reaction times of responses were significantly shorter to the discriminative cue predictive of high reward magnitude. Indirect stimulation of dopamine receptors in the ACB by d‐amphetamine (20 µg/0.5 µL) decreased reaction times, impaired their guidance by cue‐associated reward magnitudes and reduced the accuracy of task performance. Blockade of AMPA/KA receptors in the ACB by 6‐cyano‐7‐nitroquino‐xaline‐2,3‐dione (0.75 and 2.5 µg/0.5 µL) or NMDA receptors by d(−)‐2‐amino‐5‐phosphonopentanoic acid (5 µg/0.5 µL) produced a general increase in reaction times, but left guidance of reaction times by cue‐associated reward magnitudes unaffected. Thus, stimulation of intra‐ACB ionotropic glutamate receptors is critically involved in modulating the speed of instrumental responding to cues predictive for reward magnitude, but is not required for intact performance of previously learned instrumental behaviour.
The growth of cat cerebral cortex in postnatal life: a magnetic resonance imaging study
Authors: Rathjen Stefan , Engelmann Ralf , Struif Stefan , Kaulisch Thomas , Stiller Detlef , Löwel Siegrid
Published: October 2003

To follow up the development of an individual brain over time and to measure its growth we have analysed the brains of individual cats from postnatal day 12 to adulthood using magnetic resonance imaging. From the anatomical images, four parameters were calculated: anteroposterior extent of the telencephalon, brain volume, neocortical surface area and neocortical volume. The development of the anteroposterior extent was similar in all cats. It increased between the 3rd and 6th postnatal week from 33 to 37.5 mm ending up ≈ 40 mm in adulthood. The brain volume showed greater variability. On average, the volume increased from 11.5 to 16.5 cm3 in the same period. Adult values were ≈ 19 cm3. Considerable interindividual variability was observed in neocortical surface area. In one cat, it expanded from 12.5 to 26 cm2 between days 14 and 41. In another cat, this area expanded from 16 to 24.5 cm2 between days 12 and 40. On average, the surface area expanded by 34% between the 3rd and 6th week. Adult values ranged from 27 to 30 cm2. Neocortical volume increased from 2.9 to 4.1 cm3 between the 3rd and 6th postnatal week and to 4.5–5.2 cm3 in adulthood. The asymmetry between the hemispheres in both neocortical surface area and volume was < 3% in all animals for most of the observation period. Comparison of the neocortical surface measurements with data on postnatal growth of cat primary visual cortex obtained by 2‐deoxyglucose autoradiography indicates that the primary visual cortex grows at the same speed and amounts to ≈ 15% of the entire neocortical surface area throughout development.
Basal and morphine‐evoked dopaminergic neurotransmission in the nucleus accumbens of MOR‐ and DOR‐knockout mice
Authors: Chefer Vladimir I. , Kieffer Brigitte L. , Shippenberg Toni S.
Published: October 2003

Conventional and no net flux microdialysis were used to quantify basal and morphine‐induced extracellular dopamine (DA) levels and the basal extraction fraction, which provides an estimate of the rate of DA uptake, in the nucleus accumbens (NAc) of wild‐type mice and those with a constitutive deletion of mu (MOR)‐ or delta (DOR)‐opioid receptors. Locomotor activity was assessed in these same animals. No difference between genotypes in basal dialysate DA levels was seen. No net flux studies revealed significant decreases in the DA extraction fraction in both MOR‐ and DOR‐knockout mice, indicating decreased basal DA uptake in both genotypes. Extracellular DA, however, was unchanged. Because extracellular neurotransmitter levels are determined by the dynamics of both release and uptake, these findings provide suggestive evidence that basal DA release is decreased in mutant mice. Systemic administration of morphine significantly increased locomotor activity and dialysate DA levels in wild‐type mice. MOR‐knockout mice failed to exhibit a behavioural response to morphine. The ability of morphine to increase DA levels, however, was reduced but not prevented. No alteration in the effects of morphine was observed in DOR‐knockout mice. These data provide genetic evidence for the existence of tonically active MOR and DOR systems that modulate basal DA neurotransmission in the NAc. Furthermore, they demonstrate that in contrast to the locomotor‐activating effects of morphine, a small component of morphine‐evoked DA release occurs independently of MOR activation.
Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task
Authors: Wallis Jonathan D. , Miller Earl K.
Published: October 2003

An important function of the prefrontal cortex (PFC) is the control of goal‐directed behaviour. This requires information as to whether actions were successful in obtaining desired outcomes such as rewards. While lesion studies implicate a particular PFC region, the orbitofrontal cortex (OFC), in reward processing, neurons encoding reward have been reported in both the OFC and the dorsolateral prefrontal cortex (DLPFC). To compare and contrast their roles, we recorded simultaneously from both areas while two rhesus monkeys (Macaca mulatta) performed a reward preference task. The monkeys had to choose between pictures associated with different amounts of a juice reward. Neuronal activity in both areas reflected the reward amount. However, neurons in the DLPFC encoded both the reward amount and the monkeys' forthcoming response, while neurons in the OFC more often encoded the reward amount alone. Further, reward selectivity arose more rapidly in the OFC than the DLPFC. These results are consistent with reward information entering the PFC via the OFC, where it is passed to the DLPFC and used to control behaviour.
Dynamic increases in dopamine during paced copulation in the female rat
Authors: Jenkins William J. , Becker Jill B.
Published: October 2003

The role of dopamine in the rewarding aspects of sexual behaviour in female rats was investigated. This is a unique model because sexual behaviour is only rewarding when copulatory stimuli are experienced at the preferred rate of copulation for a female rat. In addition, increases in dopamine in the nucleus accumbens occur during sexual behaviour only when the female achieves this preferred rate of copulation. In this study, minute‐by‐minute changes in nucleus accumbens dopamine were monitored using in vivo microdialysis. We report here that extracellular dopamine in the nucleus accumbens increases before coital stimulation only when sexual behaviour is occurring under conditions that are rewarding to the female rat. We conclude that increases in dopamine in the nucleus accumbens are involved in anticipation, not consummation, of sexual behaviour in the female rat.
A comparison of different models of stroke on behaviour and brain morphology
Authors: Gonzalez C.L.R. , Kolb B.
Published: October 2003

We compared the effects of three models of permanent ischemia, as well as cortical aspiration, on behaviour and brain morphology. Rats received a stroke either by devascularization or by two different procedures of medial cerebral artery occlusion (MCAO; small vs. large). Animals were trained in a reaching task, forepaw asymmetry, forepaw inhibition, sunflower seed task and tongue extension. Behaviour was assessed 1 week after the lesion and at 2‐week intervals for a total of 9 weeks. One week after the surgery all animals were severely impaired on all tasks and although they improved over time they only reached preoperative base lines on tongue extension. Animals with small MCAOs performed better in reaching and sunflower tasks; no other behavioural differences were detected among the groups. Pyramidal cells in forelimb and cingulate areas as well as spiny neurons of the striatum were examined for dendritic branching and spine density using a Golgi–Cox procedure. Each lesion type had a different impact on cell morphology. Overall, different changes (atrophy or hypertrophy) were observed with each kind of lesion and these changes were specific for the region (forelimb, cingulate, striatum) and the condition (intact vs. damaged hemisphere). These results suggest that: (i) different lesions to the motor cortex produce subtle differences in behaviour, and (ii) the method used to induce the lesion produces striking differences in cortical and subcortical plasticity.
Up‐regulation of fatty acid metabolizing‐enzymes mRNA in rat spinal cord during persistent peripheral local inflammation
Authors: Benani A. , Vol C. , Heurtaux T. , Asensio C. , Dauça M. , Lapicque F. , Netter P. , Minn A.
Published: October 2003

Persistent peripheral inflammation is associated with repetitive painful inputs into the spinal cord, leading to a chronic pain state. Related dramatic changes occur in the central nervous system (CNS) including central sensitization, which results in hyperalgesia. This neural plasticity involves in part fatty acids as functional and structural compounds. We hypothesized that central modification of fatty acids metabolism might occur after prolonged peripheral noxious stimulation. In the present study, the regulation of genes involved in fatty acids metabolism in the rat CNS was investigated during a chronic pain state. Using semiquantitative RT‐PCR, we explored in the neuraxis the mRNA expression of brain acyl‐CoA synthetases (ACS) and acyl‐CoA oxidase (ACO), which are major fatty acid‐metabolizing enzymes, following complete Freund's adjuvant (CFA) injection into a hind paw. Similar spinal up‐regulation of the isoforms ACS2, ACS3, ACS4, and of ACO was detected early after 30 min, reaching a maximal after 6 h post‐injection. Other peaks were also observed after 4 and 21 days post‐inoculation, corresponding to the acute and chronic inflammation, respectively. Induction occurred only in the lumbar spinal cord ipsilaterally to the inflamed paw and was completely inhibited by a local anaesthesia of the sciatic nerve, suggesting a neural transmission of the inducing signal. Moreover, intrathecal injection of MK801, a noncompetitive NMDA antagonist, partially prevented these inductions, highlighting the involvement of the neurotransmitter glutamate in the central ACS and ACO up‐regulation. These findings suggest that the fatty metabolism is stimulated in the CNS during a chronic pain state.
Extrinsic regulation of injury/growth‐related gene expression in the inferior olive of the adult rat
Authors: Buffo Annalisa , Carulli Daniela , Rossi Ferdinando , Strata Piergiorgio
Published: October 2003

Successful axon regeneration relies on the capability of the lesioned neurons to up‐regulate a specific set of injury/growth‐associated genes. In the adult central nervous system, the strength of the cell body response is generally related to the distance of the injury site from the perikaryon, being stronger for proximal lesions. Nevertheless, inferior olive (IO) cells react to injury and regenerate their axons even after distal transections. To investigate the mechanisms that regulate the IO growth properties, we examined the expression of injury/growth markers (nitric oxide synthase, growth‐associated protein 43 and c‐Jun) after target deletion or axotomy performed at different sites along the olivocerebellar pathway. Both axon injury and target loss disclose two subsets of IO neurons distributed within precise subnuclei: one subset up‐regulates all markers in all conditions, whereas the other shows a mild c‐Jun expression but remains unresponsive even after a very proximal axotomy. These observations indicate that distinct subpopulations of IO cells respond to different regulatory strategies. Unresponsive neurons appear insensitive to environmental positive or negative cues, suggesting that they are intrinsically unable to set up a cellular reaction to injury. In contrast, cell body changes in reactive neurons are elicited after the removal of retrogradely transported target‐derived inhibitory signals. Target loss also induces degeneration of IO cells, whose survival remains partially dependent on Purkinje targets in adulthood. Thus, the intrinsic regenerative potential of a functionally homogeneous population is regulated by multiple mechanisms, specific for distinct neuronal subsets.
Transplantation of glial cell line‐derived neurotrophic factor‐expressing cells into the striatum and nucleus accumbens attenuates acquisition of cocaine self‐administration in rats
Authors: Green‐Sadan Tamar , Kinor Noa , Roth‐Deri Ilana , Geffen‐Aricha Revital , Schindler Cheryl J. , Yadid Gal
Published: October 2003

Neurotrophic factors, such as glial cell line‐derived neurotrophic factor (GDNF), may play a role in drug‐induced biochemical and behavioural adaptations that characterize addiction. We found that GDNF mRNA levels are lower in the striatum of rats that chronically self‐administered cocaine. Therefore, we examined the effect of transplanted cells used as a biodelivery system for GDNF on cocaine self‐administration in rats. A human astrocyte‐like cell line, which produces and excretes GDNF, was transplanted into the striatum and nucleus accumbens of rats. These rats showed a significantly lower number of active lever presses in the cocaine self‐administration paradigm compared with control rats. Moreover, rats that received a chronic infusion of GDNF via a micro‐osmotic pump also exhibited weak cocaine self‐administration. Therefore, we conclude that exogenous augmentation of GDNF repositories may be useful in suppressing cocaine self‐administration.
Predictive and reactive co‐ordination of grip and load forces in bimanual lifting in man
Authors: Bracewell R. Martyn , Wing Alan M. , Soper Harriet M. , Clark Kristen G.
Published: October 2003

We investigated the intra‐ and inter‐manual coordination of grip force (GF) and load force (LF) during bimanual lifting and holding of a single object. In a voluntary task involving lifting a predictable load (Experiment 1), we showed scaling of GF to LF generated by either hand, similar to effects seen in previous unimanual studies. Moreover, the GF rates generated by the two hands were correlated. In part this correlation was due to the correlation between the LF rates. However, the GF rates remained correlated when the effects of the correlation in LF rates were partialled out. This novel finding suggests an additional co‐ordinative constraint at the level of specification of GFs. As a contrast to the predictable loading in the first experiment, in the second experiment loading was temporally unpredictable and elicited reactive increases in GF. In Experiment 2, the intermanual correlation of GF rates was stronger than in Experiment 1. We speculate that this result reflects greater degrees of co‐ordinative constraint at lower levels in the motor control hierarchy.
Temporal aspects of spatial task performance during intermittent hypoxia in the rat: evidence for neurogenesis
Authors: Gozal David , Row Barry W. , Gozal Evelyne , Kheirandish Leila , Neville Jennifer J. , Brittian Kenneth R. , Sachleben Leroy R. , Guo Shang Z.
Published: October 2003

Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea, leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in the adult rat. We report that in Sprague–Dawley rats the initial IH‐induced impairments in spatial learning are followed by a partial functional recovery over time, despite continuing IH exposure. These functional changes coincide with initial decreases in basal neurogenesis as shown by the number of positively colabelled cells for BrdU and neurofilament in the dentate gyrus of the hippocampus, and are followed by increased expression of neuronal progenitors and mature neurons (nestin and BrdU‐neurofilament positively labelled cells, respectively). In contrast, no changes occurred during the course of IH exposures in the expression of the synaptic proteins synaptophysin, SNAP25, and drebrin. Collectively, these findings indicate that the occurrence of IH during the lights on period results in a biphasic pattern of neurogenesis in the hippocampus of adult rats, and may account for the observed partial recovery of spatial function.
Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation
Authors: Kelly Sara , Jhaveri Maulik D. , Sagar Devi R. , Kendall David A. , Chapman Victoria
Published: October 2003

The presence of cannabinoid1 (CB1) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl‐2‐choroethylamide (ACEA; 10 and 30 µg in 50 µL), a selective CB1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 µg in 50 µL) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 ± 4% of control; P < 0.01) and inflamed (12 ± 8% of control; P < 0.05) rats. Similarly, noxious (80 g) mechanically evoked responses of spinal neurons were inhibited by peripheral injection of ACEA (30 µg in 50 µL) in noninflamed rats (51 ± 9% of control; P < 0.01) and rats with peripheral carrageenan inflammation (21 ± 8% of control; P < 0.01). Inhibitory effects of ACEA were significantly greater in rats with peripheral carrageenan inflammation than in noninflamed rats (P < 0.05). Inhibitory effects of ACEA were significantly blocked by coadministration of the CB1 receptor antagonist SR141716A in both groups of rats. Peripheral injection of SR141716A alone did not alter mechanically evoked responses of spinal neurons in either group of rats. These data demonstrate that activation of peripheral CB1 receptors can inhibit innocuous and noxious somatosensory processing. Furthermore, following peripheral inflammation there is an enhanced inhibitory effect of a peripherally administered CB1 receptor agonist on both innocuous and noxious mechanically evoked responses of spinal neurons.
MuSC is involved in regulating axonal fasciculation of mouse primary vestibular afferents
Authors: Kawauchi Daisuke , Kobayashi Hiroaki , Sekine‐Aizawa Yoko , Fujita Shinobu C. , Murakami Fujio
Published: October 2003

Regulation of axonal fasciculation plays an important role in the precise patterning of neural circuits. Selective fasciculation contributes to the sorting of different types of axons and prevents the misrouting of axons. However, axons must defasciculate once they reach the target area. To study the regulation of fasciculation, we focused on the primary vestibulo‐cerebellar afferents (PVAs), which show a dramatic change from fasciculated axon bundles to defasciculated individual axons at their target region, the cerebellar primordium. To understand how fasciculation and defasciculation are regulated in this system, we investigated the roles of murine SC1‐related protein (MuSC), a molecule belonging to the immunoglobulin superfamily. We show: (i) by comparing 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (Dil) labelling and anti‐MuSC immunohistochemistry, that downregulation of MuSC in PVAs during development is concomitant with the defasciculation of PVA axons; (ii) in a binding assay with cells expressing MuSC, that MuSC has cell‐adhesive activity via a homophilic binding mechanism, and this activity is increased by multimerization; and (iii) that MuSC also displays neurite outgrowth‐promoting activity in vestibular ganglion cultures. These findings suggest that MuSC is involved in axonal fasciculation and its downregulation may help to initiate the defasciculation of PVAs.
Networks of inhibitory and excitatory commissural interneurons mediating crossed reticulospinal actions
Authors: Bannatyne B. Anne , Edgley Stephen A. , Hammar Ingela , Jankowska Elzbieta , Maxwell David J.
Published: October 2003

Axonal projections and neurotransmitters used by commissural interneurons mediating crossed actions of reticulospinal neurons were investigated in adult cats. Eighteen interneurons, located in or close to lamina VIII in midlumbar segments, that were monosynaptically excited by reticulospinal tract fibres and projected to contralateral motor nuclei were labelled by intracellular injection of tetramethylrhodamine‐dextran and Neurobiotin. The nine most completely labelled interneurons were analysed with combined confocal and light microscopy. None of the stem axons gave off ipsilateral axon collaterals. Seven cells had axon collaterals that arborized in the contralateral grey matter in the ventral horn of the same segments. Transmitters were identified by using antibodies raised against vesicular glutamate transporters 1 and 2, glutamic acid decarboxylase and the glycine transporter 2. The axons of two cells were immunoreactive for the glycine transporter 2 and hence were glycinergic. Three cells were immunoreactive for the vesicular glutamate transporter 2 and hence were glutamatergic. None of the axons displayed immunoreactivity for glutamic acid decarboxylase. Electron microscopy of two cells revealed direct synaptic connections with motoneurons and other neurons. Axonal swellings of one neuron formed synapses with profiles in motor nuclei whereas those of the other formed synapses with other structures, including cell bodies in lamina VII. The results show that this population of commissural interneurons includes both excitatory and inhibitory cells that may excite or inhibit contralateral motoneurons directly. They may also influence the activity of motoneurons indirectly by acting through interneurons located outside motor nuclei in the contralateral grey matter but are unlikely to have direct actions on interneurons in the ipsilateral grey matter.
A review of basal insulins
Authors: Barnett Anthony H.
Published: October 2003

Tight glycaemic control (ideally, HbA1c < 7%) is central to reducing the risk of long‐term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted‐acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter‐ and intra‐patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long‐acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes.
Comparability of venous and capillary glucose measurements in blood
Authors: Colagiuri S. , Sandbæk A. , Carstensen B. , Christensen J. , Glumer C. , Lauritzen T. , Borch‐Johnsen K.
Published: October 2003

Aim  Diabetes and glucose intolerance are diagnosed by measurement of glucose in blood. Glucose is usually measured as venous plasma or capillary whole blood and diagnostic criteria frequently provide equivalence estimates for these two methods. This study examined the relationship between glucose measured in capillary and venous samples collected at random, fasting and 2 h after oral glucose.

Methods  Simultaneous measurements of venous plasma and capillary blood glucose were performed on random samples in 609 people, fasting samples in 685 people, and 2 h after oral glucose samples in 463 people. Separate capillary and venous samples were collected each time. A variance component model was used to construct conversion algorithms between venous and capillary results.

Results  The relationship between venous and capillary glucose values varied, with venous plasma being higher than capillary blood for random and fasting samples but lower for sampling 2 h after oral glucose. Discrepancies were observed between measured capillary blood values and the published WHO capillary blood equivalence values for venous plasma values for all except a fasting venous value of 7.0 mmol/l. For example, for a fasting venous plasma glucose of 6.1 mmol/l the WHO equivalent value is 5.6 mmol/l, while the measured value was 5.2 mmol/l, and for a 2‐h venous plasma glucose of 11.1 mmol/l the WHO value is 11.1 mmol/l, while the measured result was 11.7 mmol/l.

Conclusions  These results highlight the difficulty in equating glucose levels from one sampling and measuring procedure to another, and raise uncertainties about current published equivalence values which could lead to misclassifications in glucose tolerance status.
The cornified cell envelope: an important marker of stratum corneum maturation in healthy and dry skin
Authors: Harding C. R. , Long S. , Richardson J. , Rogers J. , Zhang Z. , Bush A. , Rawlings A. V.
Published: October 2003

Synopsis

The cornified cell envelope (CE) formed by transglutaminase‐mediated ε‐(γ‐glutamyl)lysine cross‐linking of specialized corneocyte proteins is the most insoluble component of the terminally differentiated keratinocyte. Under normal Nomarski optics, two types of CE are readily distinguishable: an irregularly shaped, readily deformed ‘fragile’ envelope (CEf), which predominates in the deepest layers of the stratum corneum, and a polygonal “resilient” or ‘rigid’ envelope (CEr), which represents over 80% of the CE population in the superficial layers. This distinct spatial distribution indicates a maturation of the CE from the fragile to the resilient morphology during stratum corneum maturation. In this study, we have examined morphological and physical changes occurring in the CE during the terminal differentiation. The proportion of CEf and CEr present in superficial samples of stratum corneum were readily distinguishable following staining with Tetrarhodamine isothiocyanate (TRITC) and showed significant body site variation. The percentage of CEf was highest on samples recovered from exposed body sites (back of hand > cheek > inner arm [bicep region]) suggesting innate body site differences or that photodamage and other environmental trauma can reduce or delay normal CE maturation. Soap‐induced dryness resulted in a significant decrease in CE maturation coincidental with reduced corneodesmosomal hydrolysis. Effective moisturization of winter‐induced dry skin enhanced CE maturation (33% increase in TRITC fluorescence, n = 14 following 4‐week treatment). Using a novel micromanipulation instrument, the force required (µN) to maximally deform individual CEf and CEr was compared. CEf recovered from deep stratum corneum were significantly softer and weaker than CEr recovered from superficial layers. These studies indicate that the normal process of CE maturation is associated with an actual strengthening of this insoluble protective structure and that the impairment of this process is associated with poor quality of the stratum corneum.
Skin‐lightening products revisited
Authors: Petit L. , Piérard G. E.
Published: October 2003

Synopsis

Skin colour typology depends on the amount and location of its chromophores. Among them, eumelanins derived from 5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA) and 5,6‐dihydroxyindole (DHI), and phaeomelanins are of utmost importance. These biomolecules result from the multi‐step enzymatic and non‐enzymatic conversion of tyrosine into melanins. Pigmentation disorders are multiple and depend on alterations in the density in active melanocytes, and on specific abnormalities of any of the complex melanogenesis mechanisms. This review presents some of the main skin‐lightening agents with respect to their mechanisms of action and side‐effects. Some of the novel compounds may lead to new perspectives in the fields of dermatology and cosmetology. The methods commonly used to assess efficacy of skin‐lightening products rely on in vitro models including cell‐free enzymatic assays, melanocyte cultures and reconstructed epidermis bioassays. Animal models have little relevance. By contrast, human testing with the support of instrumental evaluations is the most informative.
A double‐blind randomized vehicle‐controlled clinical trial investigating the effect of ZnPTO dose on the scalp vs. antidandruff efficacy and antimycotic activity
Authors: Bailey P. , Arrowsmith C. , Darling K. , Dexter J. , Eklund J. , Lane A. , Little C. , Murray B. , Scott A. , Williams A. , Wilson D.
Published: October 2003

Synopsis

Dandruff is a common problem in approximately 30% of the world's population. Reports in the literature regarding treatment of this condition with various antidandruff shampoos usually report the level of active ingredient within the formulation. However, we propose that a more important parameter relating to antidandruff efficacy is the amount of active ingredient delivered to the scalp from the shampoo. This report describes the results from two studies designed to investigate the relationship between the level of zinc pyrithione (ZnPTO) deposited onto the scalp and the resultant scalp condition. A double‐blind randomized vehicle‐controlled clinical study comparing three shampoos – a vehicle, a low‐depositing ZnPTO shampoo and a high‐depositing ZnPTO shampoo – was carried out in the U.K. with 53 panelists with dandruff or mild‐to‐moderate seborrheic dermatitis of the scalp. Both shampoos containing ZnPTO were significantly superior in antidandruff efficacy to the vehicle. Furthermore, the high‐depositing ZnPTO shampoo was significantly superior compared with the low‐depositing ZnPTO shampoo in terms of both antidandruff efficacy and antimycotic activity. Antidandruff performance and antimycotic activity of ZnPTO‐containing shampoos is highly dependent on the amount of active ingredient delivered to the scalp. Furthermore, careful manipulation of the formulation parameters of an antidandruff shampoo can result in enhanced levels of delivery of the active ingredient without having to increase the level of active ingredient within the formulation.
Effect of antiperspirants on whole body sweat rate and thermoregulation
Authors: Burry J. S. , Evans R. L. , Rawlings A. V. , Shiu J.
Published: October 2003

Synopsis

It is well established that the evaporation of sweat from the human body surface is the main mechanism by which heat balance is maintained following a rise in body core temperature. Since the introduction of the first brand name antiperspirant in the United States during the early 1900s, antiperspirant products designed to control underarm wetness have grown to represent one of the largest cosmetic categories in most global markets. However, although axillary sweating only constitutes less than 1% of whole body sweat rate, consumers, particularly in hot countries, have begun to articulate the concern that antiperspirants may interfere with the body's natural cooling process. To investigate this, we undertook carefully designed experiments that measured the effects of axillary antiperspirant application on whole body sweat rate and body core temperature, following a regimen of exercise‐induced heat stress in a hot environment in human volunteers. Our data show clearly that although antiperspirant prevents sweat production in the axillary area, this does not impact the ability of the body to thermoregulate following a rise in body core temperature. Thus, recent consumer questioning over this aspect of antiperspirant use appears to be unwarranted.
Do cosmetics enhance female Caucasian facial attractiveness?
Authors: Mulhern R. , Fieldman G. , Hussey T. , Lévêque J.‐L. , Pineau P.
Published: October 2003

Synopsis

This study sought to investigate whether cosmetics do improve female facial attractiveness, and to determine whether the contribution of different cosmetic products are separable, or whether they function synergistically to enhance female beauty. Ten volunteers were made up by a beautician under five cosmetics conditions: (i) no make‐up; (ii) foundation only; (iii) eye make‐up only; (iv) lip make‐up only; and (v) full facial make‐up. Male and female participants were asked to view the 10 sets of five photographs, and rank each set from most attractive to least attractive. As predicted, faces with full make‐up were judged more attractive than the same faces with no make‐up. Sex differences within the results were also apparent. Women judged eye make‐up as contributing most to the attractiveness. Men rated eye make‐up and foundation as having a significant impact on the attractiveness of a full facial makeover. Surprisingly, lipstick did not appear to contribute to attractiveness independently.
Acetazolamide as a vasodilatory stimulus in cerebrovascular diseases and in conditions affecting the cerebral vasculature
Authors: Settakis G. , Molnár C. , Kerényi L. , Kollár J. , Legemate D. , Csiba L. , Fülesdi B.
Published: October 2003

Pathologic processes affecting the brain vessels may damage cerebral vasodilatory capacity. Early detection of cerebral dysfunction plays an important role in the prevention of cerebrovascular diseases. In recent decades acetazolamide (AZ) has frequently been used for this purpose. In the present work the mechanism of action and the previous studies are reviewed. The authors conclude that AZ tests are useful in cerebrovascular research. Further investigations are recommended to prove how impaired reserve capacity and reactivity influence the stroke risk in patients and whether these tests may indicate therapeutic interventions.
Multiple progressive intracerebral hemorrhages due to an angiosarcoma: a case report
Authors: Mühlau M. , Schlegel J. , Von Einsiedel H. G. , Conrad B. , Sander D.
Published: October 2003

Identification of intracerebral hemorrhage (ICH) and the underlying cause is a common clinical problem. Rare causes of ICH can be particularly difficult to diagnose. We describe a man on oral anticoagulation with multiple progressive ICHs, who initially showed no signs of a malignant disease. After normalisation of all coagulation tests, the ICHs continued to spread. Autopsy examination revealed an angiosarcoma. Multiple progressive ICHs caused by an angiosarcoma that mainly affects the brain have not yet been described. In the presence of normal coagulation tests, further progression of ICH should raise questions about common causes of ICH such as oral anticoagulation in our case.
Effects of microinjected small GTPases on the actin cytoskeleton of human neutrophils
Authors: Bird Margaret M. , Lopez‐Lluch Guillermo , Ridley Anne J. , Segal A. W.
Published: October 2003

This paper describes a method for microinjection of proteins (Rho GTPases) into neutrophils and observations on the responses of the cells to these injections. Neutrophils are extremely difficult to inject because of their small size, complex morphology and fragility. To allow microinjections they must be cultured on a substrate that enables them to settle, adhere and spread. We determined that fibronectin‐ and/or collagen‐coated coverslips are the best substrates and we used very fine needles and short microinjection times to minimize cell damage. These methods permitted us to inject up to 100 cells in a single preparation over a period of 30 min. Effects of microinjection were assessed by using tetramethylrhodamine isothiocyanate (TRITC)‐phalloidin to label F‐actin filaments, and observation by fluorescence and confocal scanning microscopy. Microinjection alone resulted in cell rounding and some changes in the F‐actin cytoskeleton but injected cells remained adherent at the substrate, were able to respond to microinjected GTPases (V12Rac, V14RhoA, V12Cdc42) and continued to be responsive to activation by exposure to fMet‐Leu‐Phe (fMLP) or O‐tetradecanoylphorbal 13‐acetate (TPA). V12Rac caused an increase in neutrophil membrane ruffling and short protrusions from the cell membrane, whereas V14RhoA induced a large increase in punctate F‐actin structures. V12Cdc42 produced focal condensation of F‐actin and induced the formation of small microspikes. The differences between these responses of neutrophils and those of other similarly treated cell types are discussed. Our findings demonstrate that microinjection is a valuable technique for studying the role of individual proteins in neutrophils.
An ontology of human developmental anatomy
Authors: Hunter Amy , Kaufman Matthew H. , McKay Angus , Baldock Richard , Simmen Martin W. , Bard Jonathan B. L.
Published: October 2003

Human developmental anatomy has been organized as structured lists of the major constituent tissues present during each of Carnegie stages 1–20 (E1–E50, ∼8500 anatomically defined tissue items). For each of these stages, the tissues have been organized as a hierarchy in which an individual tissue is catalogued as part of a larger tissue. Such a formal representation of knowledge is known as an ontology and this anatomical ontology can be used in databases to store, organize and search for data associated with the tissues present at each developmental stage. The anatomical data for compiling these hierarchies comes from the literature, from observations on embryos in the Patten Collection (Ann Arbor, MI, USA) and from comparisons with mouse tissues at similar stages of development. The ontology is available in three versions. The first gives hierarchies of the named tissues present at each Carnegie stage (http://www.ana.ed.ac.uk/anatomy/database/humat/) and is intended to help analyse both normal and abnormal human embryos; it carries hyperlinked notes on some ambiguities in the literature that have been clarified through analysing sectioned material. The second contains many additional subsidiary tissue domains and is intended for handling tissue‐associated data (e.g. gene‐expression) in a database. This version is available at the humat site and at http://genex.hgu.mrc.ac.uk/Resources/intro.html/), and has been designed to be interoperable with the ontology for mouse developmental anatomy, also available at the genex site. The third gives the second version in GO ontology syntax (with standard IDs for each tissue) and can be downloaded from both the genex and the Open Biological Ontology sites (http://obo.sourceforge.net/)
A simple method of culture of 11.5‐day‐old rat embryos in DMEM/F12 and 20% fetal bovine serum
Authors: Ornoy A. , Yacobi S. , Yaffee P.
Published: October 2003

Post‐implantation mouse and rat embryos are usually cultured in sera obtained from various rodents and from humans. We describe here a simple and inexpensive culture medium – Dulbecco's minimal essential medium/Ham's F12 (DMEM/F12) supplemented with 20% fetal bovine serum (FBS) – in which E11.5 rat embryos of the Hebrew University Sabra strain grow for 28 h slightly better than in heat‐inactivated 90% rat serum with 10% distilled water and addition of 1 mg mL−1glucose. They have good growth and development and a low rate of anomalies, similar to that observed in embryos cultured on rat serum. Their size, total score and olfactory system development is slightly higher than in rat embryos cultured in rat serum. About 7.2% of these embryos exhibit subcutaneous haemorrhages in various areas, but these do not seem to interfere with their growth and development. This method is not appropriate for younger embryos; in E10.5 embryos cultured for 28 h we found increased embryonic death and anomalies.