Communicating chronic hydrocephalus: A review.

Formerly called normal pressure hydrocephalus, communicating chronic hydrocephalus (CCH) is a condition affecting 0.1 to 0.5% of patients over 60years of age. The pathophysiology of this disease is poorly understood, but a defect in cerebrospinal fluid (CSF) resorption appears to be commonly defined as the cause of the neurological disorders. The last important discovery is the description of the glymphatic system and its implication in CCH and CSF resorption. Comorbidities (Alzheimer's disease, microangiopathy, parkinsonism) are very frequent, and involve a diagnostic challenge. The clinical presentation is based on the Hakim and Adams triad, comprising gait disorders, mainly impairing walking, cognitive disorders, affecting executive functions, episodic memory, visuospatial cognition, and sphincter disorders as urinary incontinence (detrusor hyperactivity). The diagnosis is suspected through a set of arguments, combining the clinical presentation, the radiological data of the magnetic resonance imaging (MRI) showing a ventriculomegaly associated with signs of transependymomous resorption of the CSF and disappearance of the cortical sulci, and the clinical response to the depletion of CSF. In the presence of all these elements, or a strong clinical suspicion, the standard treatment will be of a permanent CSF shunt, using a ventriculoatrial or ventriculoperitoneal shunt. The effectiveness of this treatment defines the diagnosis. The clinical improvement is better when treatment occurs early after the onset of the disorders, reaching 75 to 90% of motor improvement.

[Palliative care for newborns: practices in a level-III unit during a 5-year period]. / Soins palliatifs en néonatologie : analyse et évolution des pratiques sur 5ans dans un centre de niveau 3.

UNLABELLED: The "Patients' rights and end-of-life care" act known as "Leonetti's Law" promulgated in 2005 has promoted the use of palliative care to avoid unreasonable obstinacy when life-sustaining treatment appears disproportionate. Very little is known about this new practice for newborns in French neonatal units. AIMS: To describe and evaluate the practice of palliative care in the newborn (mode of entry, characteristics, and modalities) and its evolution over time. PATIENTS AND METHODS: Ambispective observational study conducted in a level III neonatal center. We included all newborns presenting conditions for which palliative care was introduced. Quantitative and qualitative analyses of routinely collected data, recorded from medical and nursing charts. We compared the recorded data between periods P1 (2006-2007) and P2 (2008-2010) using the Chi(2) test to assess changes over time. RESULTS: A total of 93 newborns benefited from palliative care during the study period. The main medical conditions motivating palliative care initiation in the newborns were severe complications of prematurity (36/93, 39%), anoxic-ischemic encephalopathy (19/93, 20.5%), severe malformations (8/93, 8.5%), severe congenital heart disease (8/93, 8.5%), and other various etiologies (22/93, 23.5%). Both the number of newborns in palliative care/total number of births and the number of deaths after palliative care/total number of neonatal deaths remained stable. In case of prenatal diagnosis (n=31), there was an increase in the number of "palliative care from birth projects" (13/22 in P2 vs. 1/9 in P1, P=0.02). Collective meetings during the decision process were significantly more frequently reported in the infants' charts in P2 (48/59 in P2 vs. 18/34 in P1, P<0.01). Withdrawing and withholding life-sustaining treatment and limiting procedures of care and/or procedures of surveillance/monitoring were more frequent in P2 as compared to P1, respectively 12/34 vs. 37/59 (P=0.02) and 14/34 vs. 39/59 (P=0.03). A titration of level III analgesics treatment was high in both periods and remained stable. However, a trend toward an increase of systematic pain evaluation over time was observed (81.6% in P2 vs. 64.5% in P1; P=0.085). CONCLUSION: A significant number of newborns affected by various pathologies undergo neonatal palliative care. Despite their recent introduction in neonatal medicine, palliative care practices have changed significantly. These practices are mostly in compliance with the "patients' rights and end-of-life care" act promulgated in France in 2005.

Accumulation of Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb in the otoliths and tissues of eel (Anguilla anguilla) following long-term exposure in an estuarine environment.

Aiming at increasing the resolution of otolith tracers, we investigated the possibility to use Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb otolith composition to retrieve the movements of eels (Anguilla anguilla) in the lower Gironde watershed. Caging experiments were designed to validate the site specific otolith signatures. Individually identified eels were reared in cages in three locations along the estuarine and river gradient. Three trials were set up for successive periods of 3 months and 6 months. Water Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb concentrations were monitored. The eel otolith composition corresponding to the experimental period was measured with an ICPMS coupled with a femtosecond laser. Liver Cd, Zn and Pb concentrations were measured. For each caging experiments, we tested the influence of individual weight gain, caging site and trial on elemental otolith concentrations. Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb were detected in eel otolith above the detection limits. Otolith Sr and Ba concentrations significantly discriminated the caging sites for one trial. Individual weight gain did not have a significant influence on otolith elemental concentrations. Co, Rb, Cd, Sn, Zn, Sr and Ba otolith concentrations were significantly influenced by the trials. Water elemental composition was only partly reflected by otolith elemental composition. The results showed that otolith composition had a more integrative value than water composition. Complex elemental seasonal variations and individual eel incorporation potential complicated the interpretation of otolith composition. Liver and otolith Cd and Zn concentrations did not show a statistically significant correlation.

The use of Eugenol and electro-narcosis as anaesthetics: transcriptional impacts on the European eel (Anguilla anguilla L.).

Ecotoxicological studies aim to assess the potential environmental risks of various products. This implies the use of various biological models and tests on live animals. In case of handling fish and mammals, ethical rules have to be respected. The use of anaesthesia is considered to be the best way to ensure animal welfare. Eugenol and electro-narcosis are among the most popular chemical and physical anaesthetics used in fisheries and by field biologists. In this study, the genetic and endocrine impacts of these anaesthetics were assessed in order to establish whether the use of such methods could skew the results of ecotoxicological studies. Twenty yellow European eels (Anguilla anguilla) were submitted to Eugenol (50mg/L) and electro-narcosis until they reached a level of deep anaesthesia, while 20 other eels were kept aware. Five anaesthetized and five unanaesthetized eels were sacrificed and analysed directly after treatment and after 1, 7 and 21 days of recovery. At the brain level, Eugenol triggered an increase in the transcription level of genes encoding proteins involved in oxidative stress responses (catalase expression 2.5-fold, mitochondrial superoxide dismutase expression 3-fold), probably due to a hypoxic event during anaesthesia. Later impacts were detected in muscles 21 days after anaesthesia (ATP synthase subunit 6 3-fold, NADH deshydrogenase subunit 5 4-fold and mitochondrial superoxide dismutase 3-fold increased) revealing oxidative stress from an accrued mitochondrial respiratory metabolism. Hormone dosages showed that the use of Eugenol reduced the release of plasma cortisol during anaesthesia. However, this impact seemed to be reversible within one day. In case of electro-narcosis, no significant variation in transcriptional levels could be detected between anaesthetized and unanaesthetized eels. Our results suggest that the use of Eugenol as an aesthetic in ecotoxicological studies measuring gene expression or plasma cortisol concentration is not appropriate, while electro-narcosis does not seem to have any impact, at least on the parameters taken into consideration in this study.

Species sympatry and horizontal transfers of Mariner transposons in marine crustacean genomes.

Mariner-like elements (MLEs) have been widely detected in terrestrial species. The first complete MLE isolated from a marine invertebrate was detected in the genome of the hydrothermal crab Bythograea thermydron by Halaimia-Toumi et al. [Halaimia-Toumi, N., Casse, N., Demattei, M.V., Renault, S., Pradier, E., Bigot, Y., Laulier, M., 2004. The GC-rich transposon Bytmar1 from the deep-sea hydrothermal crab, Bythograea thermydron, may encode three transposase isoforms from a single ORF. J. Mol. Evol. 59, 747-760] and called Bytmar1. Here, we report the isolation of three new Bytmar1 relatives from the genomes of one hydrothermal amphipod Ventiella sulfuris (Vensmar1) and two coastal crustacea, Maia brachydactila (Maibmar1) and Cancer pagurus (Canpmar1). Like Bytmar1, these MLEs have an unusually high GC content, a high CpG ratio, and a low TpA ratio. Their consensus sequence encodes a transposase that is preceded by an N-flag, as in Bytmar1, which could be a marine feature. Only one of the 19 clones obtained, Vensmar1.3, encoded for a full-length transposase. The phylogenetic analyses revealed that all these Bytmar1-related elements can be differentiated into two clusters, corresponding to the coastal or hydrothermal origin of their hosts. They also confirmed that the irritans sub-family comprises at least four lineages that seem to depend on the taxonomical position and habitat of their hosts. Finally, we observed that elements coding for two potentially complete transposases exhibiting 99.5% similarity, Bytmar1.11 and Vensmar1.3, were present in the genome of two distantly related hydrothermal crustacea, one Amphipod and one Decapod. The hypothesis of horizontal transfers is discussed in the light of the sequence similarities observed.

[4-Aza-2,3-didehydropodophyllotoxins: new lignan with antitumor activity obtained from one-step synthesis]. / 4-aza-2,3-didéhydropodophyllotoxines: nouveaux lignanes à activité antitumorale obtenus par une synthèse en une seule étape.

Podophyllotoxin, a natural lignan, is a good inhibitor of tubulin polymerization with antitumoral properties but it is too toxic for therapeutic use. In order to obtain less toxic drugs, several heterolignans have been prepared. We presented the synthesis and preliminary pharmacological properties of 4-aza-2,3-didehydropodophyllotoxins (dihydropyrrole [3,4-b]quinolin-1-ones), a new azalignan series. A straightforward synthesis was described according to a multicomponent reaction in a one-pot procedure. Starting from an aniline, an aromatic aldehyde, and a cyclic B-diketone, many substituted analogues could be prepared. Our lead, the 4-aza-2,3-didehydropodophyllotoxin, is extremely cytotoxic on various tumor cell lines, active in vivo on murine tumors. Like podophyllotoxin, this drug inhibits microtubule assembly without any effect on depolymerization.

Characteristics of pathogenic and mutualistic relationships of ascoviruses in field populations of parasitoid wasps.

Ascoviruses are disseminated among larvae in lepidopteran populations by parasitic wasps during oviposition. Ascovirus relationships with these wasps vary from pathogenic to mutualistic, and experimentally can be shown possibly to be commensal non-pathogenic virus having little or no effect. Most ascoviruses are pathogens that female wasps vector mechanically. Other ascoviruses have a more intimate relationship with their wasp vectors in that their genome is stably maintained in all wasp nuclei through several generations by vertical transmission. In this relationship, these viruses are mutualistic, enhancing the successful development of the wasp larvae by suppressing lepidopteran defence mechanisms. The DpAV4 ascovirus is a mutualist in certain Diadromus wasps but is pathogenic or not when vectored by other species of this genus. These various biologies suggest that ascovirus/wasp relationships depend on wasp regulatory factors that control virus replication. Thus, certain ascoviruses can potentially have either a pathogenic, mutualistic, or non-pathogenic relationship with a specific wasp vector, the type of relationship being dependent upon the species system in which the relationship evolved. Finally, because ascoviruses appear to be related to ichnoviruses (Polydnaviridae), the DpAV4/Diadromus system constitutes a possible interesting intermediate between the pathogenic ascoviruses and symbiotic viruses that evolved to be ichnoviruses.

The Acrolepiopsis assectella silk cocoon: kairomonal function and chemical characterisation.

Two soluble sericin-like polypeptides, B1 and B2, from leek moth (Acrolepiopsis assectella) cocoons trigger host-acceptance behaviour in the parasitoid, Diadromus pulchellus (Proc. Roy. Soc. London B 269 (2002) 1879). We found that these polypeptides were particularly cysteine-rich and lost their ability to trigger host-acceptance behaviour after being denatured and purified. This suggests that inter-disulphide bonds and the secondary structure of B1 and B2 are important for their biological activity. We also isolated six insoluble polypeptides (or polypeptides of low solubility) from A. assectella cocoons. At least four of these polypeptides triggered host-acceptance behaviour. The strongest responses were observed with P22, a light-chain fibroin or a seroin-peptide, and P100, a sericin-like polypeptide that is probably more strongly associated with the silk core than are B1 and B2. In conclusion, several polypeptides from different parts of the A. assectella silk-cocoon (the insoluble core and coating of the silk thread) are able to elicit host-acceptance behaviour in D. pulchellus females. These polypeptides belong to different silk protein families and are used as kairomones by this specialist parasitoid.

The GC-rich transposon Bytmar1 from the deep-sea hydrothermal crab, Bythograea thermydron, may encode three transposase isoforms from a single ORF.

Mariner-like elements (MLEs) are classII transposons with highly conserved sequence properties and are widespread in the genome of animal species living in continental environments. We describe here the first full-length MLE found in the genome of a marine crustacean species, the deep-sea hydrothermal crab Bythograea thermydron (Crustacea), named Bytmar1. A comparison of its sequence features with those of the MLEs contained in the genomes of continental species reveals several distinctive characteristics. First, Bytmar1 elements contains an ORF that may encode three transposase isoforms 349, 379, and 398 amino acids (aa) in long. The two biggest proteins are due to the presence of a 30- and 49-aa flag, respectively, at the N-terminal end of the 349-aa cardinal MLE transposase. Their GC contents are also significantly higher than those found in continental MLEs. This feature is mainly due to codon usage in the transposase ORF and directly interferes with the curvature propensities of the Bytmar1 nucleic acid sequence. Such an elevated GC content may interfere with the ability of Bytmar 1 to form an excision complex and, in consequence, with its efficiency to transpose. Finally, the origin of these characteristics and their possible consequences on transposition efficiency are discussed.

CAY-1, a novel antifungal compound from cayenne pepper.

CAY-1, a novel saponin from Capsicum frutescens (commercially known as cayenne pepper) was investigated to determine its in vitro antifungal activity, mechanism of action and mammalian cell cytotoxicity. CAY-1 was active against 16 different fungal strains, including Candida spp. and Aspergillus fumigatus [minimum inhibitory concentrations (MIC) ranging from 4 to 16 microg ml(-1)], and was especially active against Cryptococcus neoformans (90% inhibition at 1 microg ml(-1)). Synergistic activity was also observed between CAY-1 and amphotericin B against Candida albicans and A. fumigatus. No significant cytotoxicity was demonstrated when CAY-1 was tested against 55 mammalian cell lines at up to 100 microg ml(-1). Importantly, CAY-1 appears to act by disrupting the membrane integrity of fungal cells.

Gustatory sensilla sensitive to protein kairomones trigger host acceptance by an endoparasitoid.

Proteins isolated from the host cocoon of Acrolepiopsis assectella (Lepidoptera: Yponomeutoidea) act as kairomones for host acceptance by the endoparasitoid wasp Diadromus pulchellus Wesmael (Hymenoptera: Ichneumonidae). In this study, morphological, ultrastructural and electrophysiological studies were carried out in order to identify the contact chemoreceptive sensilla on the parasitoid antennae that perceive the protein kairomones. Three types of sensillum on the antennae of the females were found to have a chemosensory function. The receptor cell(s) of one sensillar type were shown to give a positive electrophysiological response to protein kairomones. This sensillar type is apically multiporous and female specific. Consequently, this sensillum could be the one implicated in the perception of the protein kairomone that triggers the host-acceptance behaviour of D. pulchellus females.

Genomic organization and transcription of satellite DNA in the ant Aphaenogaster subterranea (Hymenoptera, Formicidae).

A satellite DNA family (APSU) was isolated and characterized in the ant Aphaenogaster subterranea. This satellite DNA is organized in tandem repeats of 162 bp and is relatively AT rich (51.9%). Sequence analysis showed a high level of homogeneity between monomers. Loss of satellite DNA has been detected in queens in relation to workers, because the amount of satellite DNA in queens is about 25% of the amount found in workers. Restriction analysis of the total DNA with methylation-sensitive enzymes suggests that this DNA is not methylated. Analysis of the electrophoretic mobility of satellite DNA on non-denaturing polyacrylamide showed that this satellite DNA is only very lightly curved. Their possible transcription was analyzed using reverse transcription and polymerase chain reaction (RT-PCR). The satellite DNA is transcribed on the two DNA strands at the same level in worker and queen pupae, as well as in worker adults.

The effect of salinity on the emergence and seedling growth of Picea mariana, Picea glauca, and Pinus banksiana.

Mining operations in areas of the boreal forest have caused salinity issues to be a major concern for reclamation. One of the factors determining successful reclamation is the ability of species to self-propagate. The effects of salinity on the seedling emergence and early growth of three boreal forest conifers: Picea mariana, Picea glauca, and Pinus banksiana were determined. Seeds were planted in sand moistened with solutions of various concentrations of sodium chloride or sodium sulfate. Seedling emergence was monitored on a daily basis and growth parameters assessed after 6 weeks. The emergence of Pinus banksiana seedlings was least affected by salinity, and at certain concentrations, emergence even appeared to be stimulated by the presence of salt. Picea glauca was the most sensitive of the species studied. Hypertrophia was observed in all species at high concentrations of Na2SO4, and an increase in salt levels caused a corresponding reduction in seedling height and weight, root length and number of lateral roots.

Effects of consolidated tailings water on red-osier dogwood (Cornus stolonifera Michx) seedlings.

As part of their tailings management, the oil sand industries plan on producing consolidated (composite) tailings (CT), in which an inorganic coagulant aid (gypsum) is added to create a non-segregating deposit. The water associated with this treatment contains potentially phytotoxic levels of sodium, sulfate, chloride, boron, aluminum, fluoride and strontium. Since CT water is expected to saturate deposits in the reclamation areas, it may affect successful reclamation of these sites. Red-osier dogwood (Cornus stolonifera Michx) was demonstrated to be relatively salt resistant and to have high potential for the reclamation of mining areas. In the present study, we used red-osier dogwood to examine the effects of CT water on the accumulation of ions within plant tissue, growth, gas exchange, water potentials and chlorophyll concentration. CT water reduced shoot lengths and dry weights in treated plants. The roots of treated plants accumulated higher concentrations of sodium and chloride than did shoots. The accumulation of sodium and chloride was accompanied by an increase in magnesium and calcium and a decrease in potassium in the roots, while the levels of potassium increased in the leaves. CT water altered gas exchange and water potentials in seedlings, and resulted in a decrease in chlorophyll's a and b. The results suggest that the mechanisms of salt resistance in red-osier dogwood seedlings involve the restriction of sodium transport from roots to shoots.

Spaceflight inhibits bone formation independent of corticosteroid status in growing rats.

Bone formation and structure have been shown repeatedly to be altered after spaceflight. However, it is not known whether these changes are related to a stress-related altered status of the corticosteroid axis. We investigated the role of corticosteroids on spaceflight-induced effects in rat pelvis and thoracic vertebrae. Thirty-six male Sprague-Dawley rats were assigned to a flight, flight control, or vivarium group (n = 12/group). Bilateral adrenalectomy was performed in six rats per group, the additional six rats undergoing sham surgery. Adrenalectomized (ADX) rats were implanted with corticosteroid pellets. On recovery from spaceflight, thoracic vertebrae and the whole pelvis were removed and processed for biochemistry, histomorphometry, or bone cell culture studies. The 17-day spaceflight resulted in decreased bone volume (BV) in the cotyle area of pelvic bones (-12%; p < 0.05) associated with approximately 50% inhibition of bone formation in the cancellous area of pelvic metaphyses and in thoracic vertebral bodies. The latter effect was associated with a decreased number of endosteal bone cells isolated from the bone surface (BS) in these samples (-42%; p < 0.05). This also was associated with a decreased number of alkaline phosphatase positive (ALP+) endosteal bone cells at 2 days and 4 days of culture, indicating decreased osteoblast precursor cell recruitment. Maintaining basal serum corticosterone levels in flight-ADX rats did not counteract the impaired bone formation in vertebral or pelvic bones. Moreover, the decreased ex vivo number of total and ALP+ endosteal bone cells induced by spaceflight occurred independent of endogenous corticosteroid hormone levels. These results indicate that the microgravity-induced inhibition of bone formation and resulting decreased trabecular bone mass in specific areas of weight-bearing skeleton in growing rats occur independently of endogenous glucocorticoid secretion.

Sequence-recognition and cleavage of DNA by a netropsin-phenazine-di-N-oxide conjugate.

We report the synthesis, DNA-binding and cleaving properties, and cytotoxic activities of R-128, a hybrid molecule in which a bis-pyrrolecarboxamide-amidine element related to the antibiotic netropsin is covalently tethered to a phenazine-di-N-oxide chromophore. The affinity and mode of interaction of the conjugate with DNA were investigated by a combination of absorption spectroscopy, circular dichroism, and electric linear dichroism. This hybrid molecule binds to AT-rich sequences of DNA via a bimodal process involving minor groove binding of the netropsin moiety and intercalation of the phenazine moiety. The bidentate mode of binding was evidenced by linear dichroism using calf thymus DNA and poly(dA-dT).(dA-dT). In contrast, the drug fails to bind to poly(dG-dC).poly(dG-dC), because of the obstructive effect of the guanine 2-amino group exposed in the minor groove of this polynucleotide. DNase I footprinting studies indicated that the conjugate interacts preferentially with AT-rich sequences, but the cleavage of DNA in the presence of a reducing agent can occur at different sequences not restricted to the AT sites. The main cleavage sites were detected with a periodicity of about 10 base pairs corresponding to approximately one turn of the double helix. This suggests that the cleavage may be dictated by the structure of the double helix rather than the primary nucleotide sequence. The conjugate which is moderately toxic to cancer cells complements the tool box of reagents which can be utilized to produce DNA strand scission. The DNA cleaving properties of R-128 entreat further exploration into the use of phenazine-di-N-oxides as tools for investigating DNA structure.

Germination, growth and gas exchange of selected boreal forest seedlings in soil containing oil sands tailings.

Greenhouse experiments were conducted to determine the effects of soil enriched in fine tailings (FT), produced by the oil sands extraction, on germination, seedling growth and physiology of several plant species of the boreal forest. The germination of seeds was initially delayed by 15% FT in dogwood (Cornus stolonifera Michx) and jack pine (Pinus banksiana Lamb) but not in white spruce [Picea glauca (Moench) Voss]. In the second set of experiments we showed that all dogwood seedlings survived 6 months of treatment with 15% FT while the survival rates of raspberry, jack pine and white spruce seedlings were reduced to 44, 55 and 94%, respectively. FT reduced root and shoot dry weights in raspberry seedlings and the number of lateral shoots in jack pine and white spruce seedlings. In raspberry and jack pine seedlings, reductions of gas exchange were recorded. The results of our study suggest that the modifications of soil chemistry, texture and structure by FT may all contribute to the observed phytotoxic effects.