Effects of mGlu1-receptor blockade on ethanol self-administration in inbred alcohol-preferring rats.

The Group I family of metabotropic glutamate receptors includes subtype 1 (mGlu1) and subtype 5 (mGlu5) receptors. This family of receptors has generated interest as potential targets for different areas of therapeutic development, including intervention for alcohol and drug abuse. Most of this interest is driven by findings showing involvement of mGlu5 receptors in the regulation of drug self-administration; however, studies examining the role of mGlu1 receptors in drug self-administration are limited. The purpose of this work was to examine the role of mGlu1-receptor antagonism in the maintenance of ethanol self-administration and the self-administration of an alternate nondrug reward, sucrose. Male alcohol-preferring inbred rats were trained to self-administer ethanol (15% vol/vol) versus water on a concurrent schedule of reinforcement, and the effect of the mGlu1-receptor antagonist JNJ16259685 (0.1-1.0mg/kg intraperitoneal [IP]) was evaluated on self-administration. The rats were then trained to self-administer sucrose (0.4% wt/vol) versus water, and the same dose range of JNJ16259685 was tested. Locomotor activity was tested in a separate assessment to evaluate potential nonspecific motor effects of the antagonist. Ethanol self-administration was dose dependently reduced by JNJ16259685. This reduction was likely due to a motor impairment as the lowest effective dose (0.1mg/kg) significantly reduced locomotor behavior. Sucrose self-administration was reduced by the highest JNJ16259685 dose (1.0mg/kg), and this reduction was also likely due to a motor impairment. Interestingly, ethanol self-administration was more sensitive to mGlu1-receptor antagonism than sucrose self-administration as lower JNJ16259685 doses reduced ethanol-reinforced responding and motor behavior. Together, these results suggest that mGlu1 receptors do not play a specific role in modulating ethanol self-administration or the self-administration of an alternate nondrug reward (i.e., sucrose).

First Report of the Aecial State of Melampsora larici-populina on Larix spp. in North America.

Melampsora larici-populina Kleb. was reported for the first time in eastern North America during 2002, on Populus spp., its telial host (1). M. larici-populina, a heteroecious rust, alternates between species of Populus and Larix. Since M. larici-populina was observed again in 2003, we investigated the possibility that its basidiospores may infect larch (Larix spp.) resulting in spermogonia and aecia. Identification of Melampsora species from aeciospore morphology is difficult but urediniospores are distinctive. This is important since the native M. medusae also alternates between Populus and Larix spp. During the spring of 2004, aecia were observed on needles of exotic (Larix decidua Mill. and L. leptolepis (Siebold and Zucc.) Gordon) and indigenous (L. laricina (K. Koch)) larch in an arboretum in Lotbinière (Quebec, Canada) where M. larici-populina has previously been found. Larch needles with yellow blister-like fructifications were collected in May 2004 and fixed on top of petri plates to allow aeciospore release onto leaves of Jackii poplar (Populus balsamifera L. × P. deltoides Marsh.). After approximately 10 days, uredinia appeared on the abaxial surface of the poplar leaves. Some of the many needles collected yielded uredinia cultures on Jackii poplars. The majority of these cultures were identified as being M. larici-populina; one was M. medusae. M. larici-populina urediniospores were 32 to 48 µm long and possessed a characteristic apical bald spot. DNA was extracted from aecia and uredinia, and the internal transcribed spacer (ITS) of the ribosomal RNA gene was amplified in real-time polymerase chain reaction (PCR) by specific primers for M. medusae or M. larici-populina created from sequences (GenBank Accession Nos. AY429656 and AY429657). The 120 base pairs target fragments amplified only with the M. larici-populina specific primers with the 14 samples that were identified as M. larici-populina by morphological characteristics of the urediniospores. No PCR amplification was obtained with M. medusae primers. These results were not unexpected since larch has been previously reported as an aecial host of M. larici-populina elsewhere (2). The ability of M. larici-populina to overwinter and complete its life cycle has important consequences since it proves that it is established and can go through sexual reproduction. A complete life cycle in eastern North America may allow M. larici-populina to generate pathogenic variation that will challenge poplar breeders in this region. References: (1) L. Innes et al. Plant Dis. 88:85, 2004. (2) G. Newcombe et al. Plant Dis. 78:1218, 1994.

Knowledge, perception and behaviour of the general public concerning the addition of fluoride in drinking water.

A telephone survey was carried out in 1994, in the Quebec City region, among 1006 people living in two municipalities where tap water is fluoridated and 1003 people living in two municipalities where there is no fluoridation. Knowledge of the main benefit associated with the use of fluoride (prevention of tooth decay) in drinking water was not different in fluorated versus non-fluoridated municipalities (20.4% vs 19.4%, p = 0.57). Knowledge of its main disadvantage (increase of dental fluorosis) was very low and similar in both groups (3.1% vs 2.0%, p = 0.11). Opposition to fluoridation was slightly higher in fluoridated areas (22.0% vs 18.3%, p = 0.04), and the use of fluoridated supplements for children was much less important in fluoridated areas (4.4% vs 12.4%, p = 0.001). No changes in the measures of association (odds ratios) were found after adjustment for the different characteristics of the participants (age, family income, education). Opposition to fluoridation was lower among those who believed their tap water was fluoridated (even if not): 19.9% vs 34.5%, p < 0.001. This study demonstrates that there is still need for public health education on the uses of fluorides.

NHPPREG: a computer program for the analysis of nonhomogeneous Poisson process data with covariates.

A program written in C is described which finds maximum likelihood estimates of regression coefficients and other relevant parameters for a point process with covariates. The data are assumed to come from a Poisson point process and may be modelled, at the user's choice, either totally parametrically or semi-parametrically. Furthermore, extra Poisson variation may be introduced, in both the parametric and semi-parametric approach, by the device of random effects. The work closely follows the theory developed by Lawless (1987).

Local structure in ionic liquids investigated by hyper-Rayleigh scattering.

A series of ionic liquids involving imidazolium, pyrrolidinium, and alkyl ammonium cations with different anions (namely, [BF(4)], [PF(6)], [TFSI], [SCN], and [(CN)(2)N]) have been studied by hyper-Rayleigh scattering (HRS), which is a powerful technique to probe the local structure of liquids in a multipolar description. The interpretation of the HRS measurements in terms of an elementary structural (ES) entity has revealed a dominating octopolar nature of ES scatterers. By combining the HRS analysis with density functional theory calculations for different-sized ion pair clusters, we show that the octopolar nature to ES hyperpolarizability in ionic liquids (ILs) originates from a complex local structure due to the formation of 'transient' ion clusters within the time of observation of HRS (~10(-12) to 10(-14) s). We emphasize that such a structural organization puts clearly into evidence the influence of nonadditive interaction processes within first shell of neighbors (<1 nm) leading to a coherent HRS structure factor in ILs.

Weighing contaminant risks and nutrient benefits of country food in Nunavik.

In view of the levels of human exposure to priority contaminants assessed in previous surveys in Nunavik, a series of risk reduction scenarios were produced to modelize the effects of different potential health advisories on limiting exposure of women of reproductive age to these contaminants, as well as on maximizing nutritional benefits derived from the consumption of country food. This paper presents part of the results, in particular as regards effects of reducing PCB intake by 46%, 65% and 86%.

Induction of interleukin-6 in axotomized sensory neurons.

RNA from rat dorsal root ganglia was analyzed in search of potentially beneficial cytokines that are induced in dorsal root ganglia by nerve injury. By reverse transcription, the PCR, and Southern blotting, interleukin-6 mRNA was detected during development but not in normal adult dorsal root ganglia, reappeared within 1 d of sciatic nerve transection, was maximally increased after 2 and 4 d, and decreased below the threshold of detection within 1 week. By RNase protection assay, interleukin-6 mRNA was consistently present in RNA from dorsal root ganglia removed from rats 4 d following transection but not in control dorsal root ganglia. Interleukin-6 bioactivity was also present in dorsal root ganglia following nerve injury. By in situ hybridization, interleukin-6 mRNA was localized within large and medium-sized axotomized neurons. In summary, some sensory neurons respond to axotomy with a brisk transient increase in synthesis of interleukin-6. Injury to the sciatic nerve also induced mRNAs for interleukin-1 beta and tumor necrosis factor-alpha in dorsal root ganglia. The inductions of interleukin-1 beta and tumor necrosis factor-alpha mRNAs were later and more sustained than that of interleukin-6 mRNA. The cellular sources of these two cytokines have not been defined.

Cyclic stretching force selectively up-regulates transforming growth factor-beta isoforms in cultured rat mesangial cells.

Glomerular distention from increased intraglomerular pressure stretches mesangial cells (MCs). Stretching MCs in culture stimulates extracellular matrix accumulation, suggesting that this may be a mechanism for glomerular hypertension-associated glomerulosclerosis. We examined whether mechanical stretching serves as a stimulus for the synthesis and activation of the prosclerotic molecule transforming growth factor (TGF)-beta, thus providing a potential system for auto-induction of extracellular matrix. Rat MCs cultured on flexible-bottom plates were subjected to cyclic stretching for up to 3 days and then assayed for TGF-beta mRNA, secretion of TGF-beta, and localization of active TGF-beta by immunostaining. MCs contained mRNA for all three mammalian isoforms of TGF-beta. Cyclic stretching for 36 hours increased TGF-beta1 and TGF-beta3 mRNA levels approximately twofold, without altering the levels of TGF-beta2 mRNA. This was followed at 48 to 72 hours by the increased secretion of both latent and active TGF-beta1. Latent, but not active, TGF-beta3 secretion also increased whereas the levels of TGF-beta2 were unaffected by mechanical force. The stretching force in this system is unequally distributed over the culture membrane. Localization of active TGF-beta by immunostaining demonstrated that the quantity of cell-associated cytokine across the culture was directly proportional to the zonal amplitude of the stretching force. These results demonstrate that stretching force stimulates MCs to selectively release and activate TGF-beta1. This mechanical induction of TGF-beta1 may help explain the increased extracellular matrix associated with intraglomerular hypertension.

Colocalization of NGF binding sites, trk mRNA, and low-affinity NGF receptor mRNA in primary sensory neurons: responses to injury and infusion of NGF.

The distributions of mRNAs for the protooncogene trk and the low-affinity NGF receptor (LNGFR) were studied by hybridization with oligonucleotide probes on sections of adult rat primary sensory and sympathetic ganglia. For comparison with high-affinity binding sites, adjacent sections were processed for NGF receptor radioautography. Among neurons in lumbar dorsal root ganglia and trigeminal ganglia, trk mRNA and NGF-binding sites were closely colocalized; this finding together with previous direct evidence in other cell types is taken to indicate that trk protein is an essential component of the high-affinity NGF receptor in adult sensory neurons. In lumbar dorsal root ganglia and trigeminal ganglia, abundant LNGFR mRNA was found in all neurons with strong 125I-NGF labeling and on additional neurons lacking high-affinity NGF-binding sites. The presence of abundant LNGFR in neurons with high-affinity receptors could be the cause and/or consequence of their ability to respond to NGF. Neurons with abundant LNGFR mRNA but few high-affinity NGF-binding sites may have receptors for other members of the neurotrophin family. In nodose ganglia, neurons with high concentrations of LNGFR mRNA greatly outnumbered the small percentage with abundant trk mRNA. Following intrathecal infusion of NGF to otherwise normal dorsal root ganglia, the concentrations of LNGFR mRNA but not those of trk mRNA and NGF-binding sites were increased in NGF-responsive neurons. The usual single normal pattern of frequency histograms of LNGFR labeling indices became bimodal in response to NGF. Concentrations of NGF-binding sites, LNGFR mRNA, and trk mRNA were all decreased by peripheral nerve transection and restored by exogenous NGF, the restoration being complete for LNGFR mRNA and partial for trk mRNA and NGF-binding sites. The data indicate that NGF can regulate both LNGFR and trk mRNAs but do not clarify the possible contribution of the LNGFR protein to high-affinity binding sites.

Seroepidemiologic study of three zoonoses (leptospirosis, Q fever, and tularemia) among trappers in Québec, Canada.

This study was undertaken to evaluate the prevalence of antibodies against Francisella tularensis, Coxiella burnetii, and certain serovars of Leptospira interrogans among trappers in Québec, Canada. Muskrat trapping was identified as a risk factor for F. tularensis infection, whereas having a cat at home apparently protected trappers against infection by L. interrogans. High percentages of control sera were positive for antibodies against C. burnetii (15%) and L. interrogans (5%), most frequently serovar bratislava. This is the first report of human infection by serovar bratislava in North America.