[Benefits and limitations of geriatric dysphagia screening tools]. / Intérêt et limites des outils de dépistage de la dysphagie en gériatrie.

This prospective study aims to evaluate both benefits and limitations of dysphagia screening tools (DePippo, EAT10, V-VST, the IOPI tongue-strength assessment) used in a geriatric unit. Among the 102 patients under study, 47 showed a dysphagia diagnosed by full logopedic examination. The sensitivity and the specificity of the screening tools were, respectively, 31,9 % and 83,6 % for EAT10, 86,9 % and 52,7 % for the V-VST and 76,6 % and 65,0 % for the DePippo test. Regarding the posterior tongue strength assessment, the threshold value of 31kPA showed an 77,3 % sensitivity and a 52,7 % specificity. Given the results obtained from the above-mentioned screening tools and their practical application limitations, the DePippo test appears to be the most convenient for a day-to-day geriatric utilization. Finally, this study outlines the necessity of confirming, in a larger sample, the reproducibility of the DePippo test as well as the interest of measuring the tongue strength among frail older people.

L'objectif de cette étude prospective était d'évaluer l'intérêt et les limites d'outils de dépistage de la dysphagie (DePippo, EAT10, V-VST, mesure de la force de langue par IOPI) lors de leur utilisation au sein d'un service de gériatrie. Parmi les 102 patients inclus, 47 présentaient une dysphagie relevée par une évaluation logopédique complète. La sensibilité et la spécificité des tests de dépistage ont été respectivement de 31,9 % et 83,6 % pour l'EAT10, de 86,9 % et 52,7 % pour le V-VST, et de 76,6 % et 65,0 % pour le test de DePippo. Concernant la force postérieure de la langue, la valeur seuil minimale de 31 kPa présentait une sensibilité de 77,3 % et une spécificité de 52,7 %. Bien que moins sensible que le V-VST, le test de DePippo (test à l'eau) est plus largement applicable aux patients fragiles hospitalisés en gériatrie. De plus, cette étude met en lumière la nécessité de préciser, au sein d'un échantillon plus large, la reproductibilité du test de DePippo et l'intérêt de la mesure de la force de langue. En conclusion, et sous réserve de son taux de reproductibilité à préciser, le test de DePippo apparaît, actuellement, être l'outil de dépistage le plus adapté à une utilisation en gériatrie.

[Analgesic efficacy of topical lidocaine for vaso-occlusive crisis in children with sickle cell disease]. / Efficacité des emplâtres de lidocaïne 5 % sur les douleurs des crises vaso-occlusives chez l'enfant drépanocytaire.

Pain associated with vaso-occlusive crisis is the main cause of hospitalization in children with sickle cell disease. Recent studies have suggested that pain might have a neuropathic component. Lidocaine patches are commonly prescribed as a topical analgesic in adult neuropathic pain. This study reports the efficacy and safety of such treatment in 6 patients with sickle cell disease, aged 6-18 years, who had been hospitalized for vaso-occlusive crisis after failure of the standard analgesic treatment. These data have led to setting up a confirmatory phase II trial, which is currently underway.

Short-term memory and the left intraparietal sulcus: focus of attention? Further evidence from a face short-term memory paradigm.

This study explored the validity of an attentional account for the involvement of the left intraparietal sulcus (IPS) in visual STM tasks. This account considers that during STM tasks, the IPS acts as an attentional modulator, maintaining activation in long-term memory networks that underlie the initial perception and processing of the specific information to be retained. In a recognition STM paradigm, we presented sequences of unfamiliar faces and instructed the participants to remember different types of information: either the identity of the faces or their order of presentation. We hypothesized that, if the left IPS acts as an attentional modulator, it should be active in both conditions, but connected to different neural networks specialized in serial order or face identity processing. Our results showed that the left IPS was activated during both order and identity encoding conditions, but for different reasons. During order encoding, the left IPS showed functional connectivity with order processing areas in the right IPS, bilateral premotor and cerebellar cortices, reproducing earlier results obtained in a verbal STM experiment. During identity encoding, the left IPS showed preferential functional connectivity with right temporal, inferior parietal and medial frontal areas involved in detailed face processing. These results not only support an attentional account of left IPS involvement in visual STM, but given their similarity with previous results obtained for a verbal STM task, they further highlight the importance of the left IPS as an attentional modulator in a variety of STM tasks.

The left intraparietal sulcus and verbal short-term memory: focus of attention or serial order?

One of the most consistently activated regions during verbal short-term memory (STM) tasks is the left intraparietal sulcus (IPS). However, its precise role remains a matter of debate. While some authors consider the IPS to be a specific store for serial order information, other data suggest that it serves a more general function of attentional focalization. In the current fMRI experiment, we investigated these two hypotheses by presenting different verbal STM conditions that probed recognition for word identity or word order and by assessing functional connectivity of the left IPS with distant brain areas. If the IPS has a role of attentional focalization, then it should be involved in both order and item conditions, but it should be connected to different brain regions, depending on the neural substrates involved in processing the different types of information (order versus phonological/orthographic) to be remembered in the item and order STM conditions. We observed that the left IPS was activated in both order and item STM conditions but for different reasons: during order STM, the left IPS was functionally connected to serial/temporal order processing areas in the right IPS, premotor and cerebellar cortices, while during item STM, the left IPS was connected to phonological and orthographic processing areas in the superior temporal and fusiform gyri. Our data support a position considering that the left IPS acts as an attentional modulator of distant neural networks which themselves are specialized in processing order or language representations. More generally, they strengthen attention-based accounts of verbal STM.

Can phonological and semantic short-term memory be dissociated? Further evidence from landau-kleffner syndrome.

Recent studies have made a distinction between short-term storage capacities for phonological information and short-term storage capacities for lexico-semantic information (R. Martin, Lesch, & Bartha, 1999). In this multiple case study, we tried to provide further evidence for the dissociability of phonological and lexico-semantic short-term memory (STM) components, by studying verbal STM in three patients who had recovered from Landau-Kleffner syndrome. Furthermore, we explored to what extent apparent dissociations between phonological and lexico-semantic STM could be related to underlying phonological and lexico-semantic processing impairments. We found clear dissociations between phonological and lexico-semantic STM measures in patients TG, JPH, and DC, whose performance was impaired in nonword immediate serial recall and in a rhyme probe task, while performance was normal for a category probe task. These patients also presented reduced phonological effects (word length, phonological similarity, phonotactic frequency) but normal lexico-semantic effects (lexicality, word imageability, word frequency) in STM. Moreover, there were no systematic correspondencies between phonological and lexico-semantic STM and phonological and lexico-semantic processing impairments. Implications for current models of STM and language processing are discussed.

An investigation of verbal short-term memory and phonological processing in four children with Williams syndrome.

Abstract Although phonological processing is generally considered to be a proficiency in Williams syndrome (WS), there are very few studies which have extensively explored phonological processing abilities in WS. In this study, we re-assessed phonological processing in WS by exploring verbal STM and phonological awareness abilities in 4 children with WS (CA: 10-12 years) and two control groups, one matched for chronological age (CA) and the other matched for verbal mental age (VA). Our results confirm and extend previous claims of preserved phonological STM in WS by showing specifically preserved STM performance for non-words, compared to both VA and CA control groups. However, we observed that this was the case only for non-words where support of phonological and lexico-semantic knowledge was minimized, with reduced phonological and lexico-semantic effects on STM performance. Furthermore, a more direct assessment of phonological processing abilities through phonological awareness tasks showed impaired performance for the 4 WS children. Our data confirm that STM for non-words represents a real strength in WS but they do not support previous assumptions of a more general preservation of phonological processing abilities in WS. Implications for impaired and preserved cognitive processes underlying verbal STM and phonological awareness abilities in WS are discussed.

Genetic structure and mating systems of metallicolous and nonmetallicolous populations of Thlaspi caerulescens.

• Genetic variation structure and breeding system were investigated in metallicolous (MET) and nonmetallicolous (NONMET) populations of the heavy-metal hyperaccumulator Thlaspi caerulescens from Belgium, Luxembourg and the French Mediterranean region. • Allozyme variation showed a clear differentiation between the two ecotypes in Belgium and Luxembourg but not in southern France, in line with the lower degree of geographical isolation between the two ecotypes in this region. • In both regions inbreeding coefficient (FIS ) of NONMET populations was significantly higher compared to MET populations. Pollen/Ovule ratios were significantly higher in MET compared with NONMET populations. • These results suggest that NONMET populations of T. caerulescens are more self-fertile than their MET counterparts. This contrasts with earlier studies on other metal-tolerant species in which selfing rates were higher in MET populations. This pattern may be explained by the fact that both ecotypes are not in sympatry in the populations studied, and therefore reproductive isolation has not been selected to maintain the adaptations to metal-contaminated soils. In addition, higher selfing rates in NONMET populations may have evolved as a mechanism of reproductive assurance, because these populations generally are at low densities.

Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function.

The present study investigated the effects of the selective neurokinin-2 (NK2) receptor antagonist SR48968 in behavioral, electrophysiological, and biochemical tests sensitive to the action of prototypical antidepressants (fluoxetine, imipramine) or to corticotropin-releasing factor (CRF) receptor antagonists, which have been proposed recently as potential antidepressants. Results showed that SR48968 (0.3-10 mg/kg i.p.) produced antidepressant-like activity because it reduced immobility in the forced swimming test in both mice and rats, and decreased the amount of maternal separation-induced vocalizations in guinea pig pups. This latter effect appears to involve a reduction of stress-induced substance P release because SR48968 reduced the separation-induced increase in the number of neurons displaying neurokinin-1 receptor internalization in the amygdala. Furthermore, SR48968 increased the expression of the cAMP response-element binding protein mRNA in the rat hippocampus after repeated (1 mg/kg i.p., 21 days), but not acute administration. Finally, neuronal firing of the locus coeruleus (LC) and noradrenergic (NE) release in the prefrontal cortex both elicited by an uncontrollable stressor or an intraventricular administration of CRF were reduced by SR48968 (0.3-1 mg/kg i.p.). The finding that SR48968 (1 mg/kg i.p.) blocked the cortical release of NE induced by an intra-LC infusion of the preferential NK2 receptor agonist neurokinin A suggested the presence of NK2 receptors in this latter region. Importantly, SR48965 (1-10 mg/kg i.p.), the optical antipode of SR48968, which is devoid of affinity for the NK2 receptor, was inactive in all the models used. These data suggest that NK2 receptor blockade may constitute a novel mechanism in the treatment of depression and CRF-related disorders.

Activity of SR141716 on post-reinforcement pauses in operant responding for sucrose reward in rats.

Cannabinoids increase food intake, via CB1 receptors. The CB1 antagonist, SR141716, has been reported to decrease palatable food consumption in both operant and non-operant procedures. Similarly, CB1 receptor blockade diminished responding for normal food pellets under a fixed-ratio 15 (FR-15) schedule of reinforcement. The present experiment investigated whether the control of a continuous schedule of reinforcement (CRF) for sucrose pellets would be sensitive to the CB1 antagonist in mildly deprived rats. SR141716 dose-dependently reduced responding in a CRF procedure, by increasing post-reinforcement pauses. Together with formerly published conclusions, the data suggest that CB1 blockade reduces the rewarding efficacy of both palatable and non-palatable food.

Blockade of cannabinoid (CB1) receptors by 141716 selectively antagonizes drug-induced reinstatement of exploratory behaviour in gerbils.

RATIONALE: A cannabinoid hypothesis of schizophrenia has been proposed according to which cognitive dysfunction could be associated with dysregulation of an endogenous cannabinoid system. OBJECTIVE: The present study investigated whether SR 141716, a selective CB1 receptor antagonist, was able to reduce the hyperactivity induced in gerbils by various stimulant drugs known to produce or exacerbate schizophrenic symptoms. METHODS: Cocaine, d-amphetamine, morphine, and Win 55212-2 were administered intraperitoneally (IP) either immediately before placing the animals in the test apparatus (non-habituated gerbils) or after a 2- to 3-h habituation period in the actimeter (habituated gerbils). SR 141716 was given IP 30 min before the injection of stimulant drugs. Horizontal activity was recorded every 10 min for 1 h in Digiscan activity monitor. RESULTS: SR 141716 (0.3-3 mg/kg) dose-dependently suppressed the enhanced locomotor activity induced by each stimulant drug in habituated gerbils, but not in non-habituated animals. Clozapine, an atypical antipsychotic compound, but not haloperidol, shared with SR 141716, the ability to differentially affect drug-induced hyperactivity in habituated versus non-habituated gerbils. CONCLUSION: The activation of cannabinoid systems is a required, permissive element in the ability of cocaine, d-amphetamine, morphine, and Win 55212-2 to reinstate behaviour, i.e., to override stimulus satiation.

SR146131: a new potent, orally active, and selective nonpeptide cholecystokinin subtype 1 receptor agonist. II. In vivo pharmacological characterization.

SR146131 is a potent and selective agonist at cholecystokinin subtype 1 (CCK1) receptors in vitro. The present study evaluates the activity of the compound in vivo. SR146131 completely inhibited gastric and gallbladder emptying in mice (ED50 of 66 and 2.7 micrograms/kg p.o., respectively). SR146131 dose dependently reduced food intake in fasted rats (from 0.1 mg/kg p.o.), in nonfasted rats in which food intake had been highly stimulated by the administration of neuropeptide Y (1-36) (from 0.3 mg/kg p.o.), in fasted gerbils (from 0.1 mg/kg p.o.), and in marmosets maintained on a restricted diet (from 3 mg/kg p.o.). SR146131 (10 mg/kg p.o.) also increased the number of Fos-positive cells in the hypothalamic paraventricular nucleus of rats. Locomotor activity of mice was reduced by orally administered SR146131 (from 0.3 mg/kg p.o.). When administered intrastriatally, SR146131 elicited contralateral turning behavior in mice. Furthermore, orally administered SR146131 (0.3-10 mg/kg), also reduced the levels of cerebellar cyclic GMP. Finally, SR146131 (0.1 microgram/kg to 1 mg/kg, p.o.) significantly and dose dependently antagonized fluphenazine-induced mouth movements in rats. The CCK1 antagonist SR27897B prevented all the effects of SR146131. Conversely, SR146131 was unable to elicit any agonist or antagonist effects in a model of CCK2 receptor stimulation in vivo. SR146131 is a very potent and selective nonpeptide CCK1 agonist in vivo. SR146131 is more potent than any other CCK1 agonists reported to date. Because pharmacodynamic studies suggest that SR146131 should have a high absolute bioavailability, it may be a promising drug for the treatment of eating and motor disorders in humans.

Targeted deletion and mutational analysis of the essential (2Fe-2S) plant-like ferredoxin in Synechocystis PCC6803 by plasmid shuffling.

The genes encoding (2Fe-2S) plant-like ferredoxins were studied in the widely used cyanobacterium Synechocystis PCC6803. The fedl gene (ssI0020) coding for the most abundant ferredoxin product was found to be expressed strongly as a light-induced monocistronic transcript, whereas the other fed genes appeared to be silent (sIr1828) or moderately expressed as polycistronic transcripts regulated by either light fluence (sIr0150, negative control) or glucose availability (sII1382). fedl was found to be critical to Synechocystis PCC6803 viability in spite of sIr0150, sII1382 or flavodoxin induction, even after the addition of glucose that compensates for the loss of photosynthesis. Nevertheless, fedl could be deleted from all chromosome copies in cells propagating a fedl gene (even of heterologous origin) on a replicating plasmid. This strain was used as the host for the subsequent introduction of fedl mutant alleles propagated on a second vector. Analysis of the fedl mutant strains generated after plasmid exchange showed that the C18-C85 disulphide bridge is not central either to the tight compaction of ferredoxin I or to its reduction by photosystem I and demonstrated that the length of the Fedl carboxy terminus is important for effective PSI/FedI interactions. The plasmid-shuffling strategy presently described has general applicability for mutational analysis of essential genes in many organisms, as it is based on promiscuous plasmids.

Biochemical and pharmacological activities of SR 144190, a new potent non-peptide tachykinin NK2 receptor antagonist.

(R)-3-(1-[2-(4-benzoyl-2-(3,4-difluorophenyl)-morpholin-2-yl)- ethyl]-4-phenylpiperidin-4-yl)-1-dimethylurea (SR 144190) is a new non-peptide antagonist of tachykinin NK2 receptors. SR 144190 potently and selectively inhibited neurokinin A binding to NK2 receptors from various species, including humans. In in vitro functional assays, it was a potent, selective and competitive antagonist of NK2 receptors with apparent affinities (pA2 values) between 9.08 and 10.10. In vivo, SR 144190 blocked [Nle10]neurokinin A-(4-10)-induced bronchoconstriction in guinea pigs (ID50 = 21 micrograms kg-1 i.v. and 250 micrograms kg-1 i.d.) and [beta Ala8]neurokinin A-(4-10)-induced urinary bladder contraction in rats (ID50 = 11 micrograms kg-1 i.v. and 190 micrograms kg-1 i.d.). It prevented citric acid-induced cough and airway hyperresponsiveness to acetylcholine in guinea pigs (1 mg kg-1 i.p.) as well as castor oil-induced diarrhoea in rats (0.01-10 micrograms kg-1 s.c. or p.o). Finally, it blocked the turning behaviour induced by intrastriatal injections of [Nle10]neurokinin A-(4-10) in mice (ID50 = 3 micrograms kg-1 i.v. and 16 micrograms kg-1 p.o.).

Three insertion sequences from the cyanobacterium Synechocystis PCC6803 support the occurrence of horizontal DNA transfer among bacteria.

Three insertion sequences were characterized from the widely-used cyanobacterium Synechocystis PCC6803. They all harbored a putative transposase sequence flanked by two imperfect inverted repeats, seemed to have duplicated their target insertion site and occurred as multiple copies in the host genome. They exhibited no obvious homology with any other cyanobacterial ISs and were termed IS5S (871 bp), IS4S (1299 bp) and ISS1987 (949 bp) because they were, respectively, homologous to IS5- and IS4-bacterial elements, and to several members of the IS630-Tc1-mariner superfamily of IS elements occurring in a wide range of hosts. This suggests that these IS-elements were spread through horizontal transfer between evolutionary distant organisms. Three IS5S-copies were isolated as a rescue insertion into a replicating plasmid (IS5Sa), or subsequently cloned from a Synechocystis DNA-library probed with IS5Sa (IS5Sb and IS5Sc), and appeared to be almost identical. In the vicinity of IS5Sb, we found the ISS1987 element inserted into the IS4S element. This indicates that the ISS1987 element has been, and could still be, mobile since its transposase sequence is not interrupted with stop codons or translational frameshifts, unlike that which is found in most members of the IS630-Tc1-mariner superfamily of transposable elements.

Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors.

SR 141716, a selective central CB1 cannabinoid receptor antagonist, markedly and selectively reduces sucrose feeding and drinking as well as neuropeptide Y-induced sucrose drinking in rats. SR 141716 also decreases ethanol consumption in C57BL/6 mice. In contrast, blockade of CB1 receptors only marginally affects regular chow intake or water drinking. The active doses of SR 141716 (0.3-3 mg/kg) are in the range known to antagonize the characteristic effects induced by cannabinoid receptor agonists. These results suggest for the first time that endogenous cannabinoid systems may modulate the appetitive value of sucrose and ethanol, perhaps by affecting the activity of brain reward systems.

Correlation between bronchoalveolar lavage (BAL) fluid cell lysate histamine content and BAL fluid eosinophil count in atopic and nonatopic asthmatics.

We have compared the bronchoalveolar lavage fluid (BAL) cellular composition and the BAL cell lysate histamine content (fluorometric assay) in 28 stable mild to moderate asthmatics (atopic n = 18 and intrinsic n = 10) and 11 control subjects. When compared to control subjects, the whole group of asthmatics had a higher proportion of BAL eosinophils (p < 0.01) and metachromatic cells (p < 0.05). The BAL cell lysate histamine was increased in atopic (p < 0.05) and intrinsic asthmatics (p < 0.05) in comparison with control subjects. In the whole group of asthmatics, the BAL cell lysate histamine content correlated with the percentage of BAL eosinophils (r = 0.58, p < 0.01). This relationship was significant in both atopic (r = 0.48, p < 0.05) and intrinsic (r = 0.70, p < 0.05) asthmatics. For the whole group of asthmatics, both the BAL cell lysate histamine and the percentage of BAL eosinophils inversely correlated with the percent predicted FEV1 (r = -0.42, p < 0.05; r = -0.51, p < 0.05). We conclude that an increased BAL cell lysate histamine content correlates with airway eosinophilic infiltration and lung function impairment in mild to moderate atopic and intrinsic asthmatics. This suggests that BAL mast cells play a key role in recruiting eosinophils in the airways of asthmatics irrespective of the presence of an atopic status.

Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist.

SR 142948A, 2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methylc arbamoyl)-2-isopropylphenyl)-1H-pyrazole3-carbonyl]amino] adamantane-2-carboxylic acid, hydrochloride, a new and extremely potent neurotensin (NT) receptor antagonist, has been characterized in comparison with SR 48692. This selective compound possesses nanomolar affinities for NT receptors, recognizes the two binding sites described for the NT receptor and fully displaces [3H]SR 48692 specific binding. SR 142948A antagonizes the classical in vitro NT effects, i.e., inositol monophosphate formation in HT 29 cells (IC50 = 3.9 nM) or intracellular calcium mobilization in Chinese hamster ovary cells transfected with the human receptor. It dose-dependently (0.04-640 x 10(-3) mg/kg p.o.) inhibits the turning behavior induced by unilateral intrastriatal injection of NT in mice, with the biphasic profile previously seen for SR 48692. At 0.1 mg/kg (i.p.), it completely antagonizes NT-evoked acetylcholine release in the rat striatum. In contrast to SR 48692, SR 142948A (p.o.) blocks both hypothermia and analgesia induced by i.c.v. injection of NT (mice and/or rats) but is unable to modify the dopamine release evoked by NT injection into the ventral tegmental area. In summary, SR 142948A retains the properties of the lead compound SR 48692 (no intrinsic agonist activity, oral bioavailability, long duration of action and good brain access), reveals a wider spectrum of activity than SR 48692 (probably due to the inhibition of NT receptor subtypes) and represents an additional tool for further exploration of the therapeutic potential of this class of compounds.

Evidence for a tachykinin/cholinergic mediation of D1 agonist-induced turning in mice.

The turning behavior induced by the intrastriatal injection of the D1 agonist (+)SKF 38393 was blocked by the two selective nonpeptide tachykinin NK1 (SR 140333) (ID50 = 0.09 mg/kg ip) and NK2 (SR 48968) (ID50 = 1.4 mg/kg ip) receptor antagonists and by atropine (ID50 = 2.6 mg/kg ip). In addition, the turning induced by the intrastriatal injection of NK1 (septide) and NK2 ([Nle10]NKA(4-10)) receptor agonists were antagonized by atropine (ID50s = 1.1 mg/kg ip and 0.78 mg/kg ip, respectively). This behavioral study shows that tachykinin receptor activation is an essential component of DA-D1/Ach interaction in the mouse striatum and confirms the previously suggested functional importance of NK2 receptors in the central nervous system.

Intrastriatal injection of cannabinoid receptor agonists induced turning behavior in mice.

When injected unilaterally into the mouse striatum, cannabinoid agonists such as Win 55212-2 (1-100 ng/mouse), CP 55940 (0.1-50 ng/mouse), and anandamide (0.5-50 ng/mouse), the putative endogenous ligand of CB1 receptor, dose-dependently induced turning behavior. SR 141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H- pyrazole-3-carboxamide hydrochloride], the selective antagonist of CB1 receptor, antagonized the three cannabinoid receptor agonists-induced turning with similar ED50s (0.13-0.15 mg/kg, IP). Spiroperidol (a D2 receptor blocker), (+)-SCH 23390 (a D1 receptor blocker), or prior 6-OHDA lesions of the striatum blocked Win 55212-2- and CP 55940-induced turning, thus suggesting the involvement of DA transmission in cannabinoid-induced turning. Taken together, these findings reinforce the notion of a cannabinoid receptor-mediated control of nigrostriatal function.