Effects of reserpine on sleep and brain biogenic amine levels in the cat

Cats receiving 0.15 mg/kg of reserpine, i.p., had rapid eye movement (REM) sleep suppressed for two days and showed increased ponto-geniculo-occipital (PGO) spikes in waking and slow-wave sleep; these effects were not reversed by administration of dopa. Reserpine (0.125 mg) given intraventricularly, however, significantly increased REM sleep and did not change the frequency of PGO spikes in waking and slow-wave sleep. The differences in sleep characteristics seen between i.p. and central administration of reserpine are probably due to (a) the marked peripheral autonomic side effects accompanying reserpine, i.p., and (b) the much smaller central depletion of brain monoamines following intraventricular reserpine. Also, the correspondance between the regional levels of brain biogenic amines and the occurrence of the sleep states is poor since REM and slow-wave were normal on the third day after reserpine, i.p., while norepinephrine and serotonin levels were depressed by about 50% at that time.This study was supported by grants MH-02211, MH-10625 and RR-05528.     

Nosocomial nasal myiasis owing to Cochliomyia hominivorax: a case in French Guiana

Abstract The larval stages of the fly Cochliomyia hominivorax are responsible for myiasis, which primarily affects wounds. We report the case of a bed-ridden patient with dementia who developed right nasal myiasis during his stay at Cayenne Hospital. Progression was favorable, but the nasal pyramid was partially destroyed. In zones where this fly is endemic, particular attention should be given to hospitalized patients with wounds and consciousness problems.     

Caspase-1 is not required for type 1 diabetes in the NOD mouse

Interleukin (IL)-1 beta and IL-18 are two cytokines associated with the immunopathogenesis of diabetes in NOD mice. Both of these cytokines are cleaved by caspase-1 to their biologically active forms. IL-1 is a proinflammatory cytokine linked to beta-cell damage, and IL-18 stimulates production of interferon (IFN)gamma in synergy with IL-12. To examine the effects produced by caspase-1 deficiency on diabetes development in NOD/Lt mice, a disrupted Casp1 gene was introduced by a speed congenic technique. Casp1(-/-) bone marrow-derived macrophages stimulated with lipopolysaccharide produced no detectable IL-18, fourfold lower IL-1 beta, and 20-30% less IL-1 alpha than macrophages from wild-type Casp1(+/+) or Casp1(+/-) controls. Unexpectedly, despite reduced IL-1 and IL-18, there was no change in the rate of diabetes or in total incidence as compared with that in wild-type NOD mice. IL-1 reportedly makes an important pathological contribution in the multidose streptozotocin model of diabetes; however, there was no difference in sensitivity to streptozotocin between NOD mice and NOD.Casp1(-/-) mice at 40 mg/kg body wt or at 25 mg/kg body wt dosage levels. These findings show that caspase-1 processing of IL-1 beta and IL-18 is not absolutely required for mediation of spontaneous or chemically induced diabetes pathogenesis in the NOD mouse.     

In vitro infection of human primary adipose cells with HIV-1: a reassessment

We reassessed the infection ability of human primary preadipocytes. The use of X4, R5 or VSV-G-pseudotyped viral particles indicated that viral entry is the limiting step. However, transfection with HIV-1 receptors restored efficient infection. Analyses of CD4, CXCR4 and CCR5 expression on preadipocytes and adipocytes revealed that receptor co-expression levels did not permit HIV-1 entry into adipose cells from all biopsies tested. We concluded that adipose tissue cannot be infected with HIV-1 in vivo.     

Role for M5 muscarinic acetylcholine receptors in cocaine addiction

Muscarinic cholinergic receptors of the M5 subtype are expressed by dopamine-containing neurons of the ventral tegmentum. These M5 receptors modulate the activity of midbrain dopaminergic neurons, which play an important role in mediating reinforcing properties of abused psychostimulants like cocaine. The potential role of M5 receptors in the reinforcing effects of cocaine was investigated using M5 receptor-deficient mice in a model of acute cocaine self-administration. The M5-deficient mice self-administered cocaine at a significantly lower rate than wild-type controls. In the conditioned place preference procedure, a classic test for evaluating the rewarding properties of drugs, M5-deficient mice spent significantly less time in the cocaine-paired compartment than control mice. Moreover, the severity of the cocaine withdrawal syndrome (withdrawal-associated anxiety measured in the elevated plus-maze) was significantly attenuated in mice lacking the M5 receptor. These results demonstrate that M5 receptors play an important role in mediating both cocaine-associated reinforcement and withdrawal.     

Application of the pulsed light technology to mycotoxin degradation and inactivation

The persistence of mycotoxins and their metabolites in agricultural products is a major safety concern because of their high resistance to all kinds of decontamination techniques. In this study, we evaluated the effectiveness of the pulsed light technology for the degradation of mycotoxins. We report that eight flashes of pulsed light destroyed of 84.5 ± 1.9, 72.5 ± 1.1, 92.7 ± 0.8 and 98.1 ± 0.2% of zearalenone, deoxynivalenol, aflatoxin B1 and ochratoxin in solution. The degradation of the molecules was monitored by HPLC and LC‐MS/MS analysis. We estimated the potential toxicity of zearalenone and deoxynivelenol after exposure to a pulsed light treatment using the Caenorhabditis elegans survival tests. The genotoxicity of aflatoxin B1 was also investigated using a complete Ames test. The results show that the treatment of zearalenone and deoxynivelenol by single or multiple flashes of pulsed light is associated with a stagnation or marginal decrease of the toxicity of the mycotoxins and that treatment of aflatoxin B1 by pulsed light can completely eliminate the mutagenic potential of this mycotoxin. This work provides the first demonstration of a nonthermal technology allowing mycotoxin destruction and inactivation of their mutagenic activity. Copyright © 2011 John Wiley & Sons, Ltd.     

Comparison of six commercial tick-borne encephalitis IgM and IgG ELISA kits and the molecular characterization of their antigenic design

Tick-borne encephalitis virus (TBEV) diagnosis is mainly based on the detection of viral-specific antibodies in serum. Several commercial assays are available, but published data on their performance remain unclear. We assessed six IgM and six IgG commercial enzyme-linked immunosorbent assay (ELISA) kits (ELISA-1 through ELISA-6) using 94 samples, including precharacterized TBEV-positive samples (n=50) and -negative samples (n=44). The six manufacturers showed satisfactory sensitivity and specificity and high overall agreement for both IgM and IgG. Three manufacturers showed better reproducibility and were the most sensitive (100%) and specific (95.5–98.1%) for both IgM and IgG. Two of them were also in agreement with the clinical interpretation in more than 90% of the cases. All the assays use inactivated virus as antigen, with strains showing approximately 94% homology at the amino acid level. The antigenic format of the assays was discussed to further improve this TBEV diagnostic tool.     

Paired-pulse facilitation and inhibition in the dentate gyrus is dependent on behavioral state

Summary It is well established that neuronal transmission from the entorhinal cortex through the dentate gyrus via the perforant path is dependent on behavioral state. To further study the modulation of neuronal transmission by behavioral state we employed the paired-pulse technique to study interneuronally-mediated inhibition and shortterm facilitation in the dentate gyrus of freely-moving rat preparations. Precisely timed double pulses of electrical stimulation were delivered to the perforant path in the chronically implanted rat preparation during each of four well-defined behavioral states: slow-wave sleep (SWS), REM sleep (REM), immobile waking (IW) or active waking with voluntary movements (AW). Evoked field potentials were recorded in the dentate gyrus and analyzed to measure the population spike amplitude which represents the total number of dentate granule cells firing in synchronous response to perforant path stimulation. The paired-pulse index (PPI) was used as a measure of the net short-term facilitation or interneuronally-mediated inhibition effective at the time of the paired-pulse test and is computed by dividing the amplitude of the second population spike (p2) by the amplitude of the first population spike (p1). During the course of this study 3754 paired-pulse tests were performed in 9 rat preparations. The three interpulse interval (IPI) values used in these studies were 25, 30 and 35 ms. The results showed that the PPI was greater during AW and REM as compared to SWS and IW. The PPI was significantly greater during AW than during SWS and IW regardless of p1 amplitude or IPI value. The PPI was significantly greater during AW than during REM under most conditions except those corresponding to low p1 amplitude and long IPI. The PPIs measured during REM were significantly greater than those measured during SWS and IW at short IPIs (25 and 30 ms) but not at an IPI of 35 ms. These results indicate that short-term facilitation is the dominant response during AW especially when observed using an IPI of 35 ms. In contrast, interneuronally-mediated inhibition was observed to be dominant during SWS and IW. The net effect during REM was observed to lie between these two extremes using an IPI of 25 ms and tended toward short-term facilitation at longer IPIs of 30 and 35 ms. Septal disinhibition of dentate granule cells is proposed as the mechanism for this effect. The behavioral state modulaion of neuronal transmission through the dentate gyrus is discussed in terms of this hypothesis. We conclude that there are probably at least two mechanisms underlying the behavioral modulation of field potentials in the dentate gyrus: (1) an indirect influence modulating the activity of inhibitory interneurons and (2) a more direct influence modulating the excitability of granule cells themselves.     

False positive in the intravenous drug self-administration test in C57BL/6J mice

The objective of this study was to examine C57BL/6J (B6) mice during extinction conditions, after food training, and for rates and patterns of operant behavior that seems similar to behavior maintained by intravenous cocaine injections. The rationale was to evaluate the potential for false positives in the intravenous self-administration test using protocols common in studies of knockout mice backcrossed to B6. An additional aim was to assess the influence of food-associated and drug-associated cues and mouse strain. Mice were allowed to acquire lever pressing reinforced by sweetened condensed milk under a fixed ratio 1 then fixed ratio 2 schedule of reinforcement accompanied by a flashing light. A catheter base was then implanted for simulation of intravenous self-administration conditions. Mice were allowed to lever press with cues remaining the same as during food training but without further scheduled consequences (i.e. no drug or food reinforcers delivered). All mice sustained lever pressing for several weeks, and over half met commonly used criteria for 'self-administration behavior.' Thus, B6 mice showed perseveration of a previously reinforced behavior that closely resembled rates and patterns of drug self-administration. This effect in B6 mice was greater than with A/J mice, and the lack of extinction was even more robust in the presence of cocaine-associated cues than with food-associated cues. We suggest that a necessary criterion for positive results in the intravenous drug self-administration test include an increase in responding when cocaine is made available after extinction with saline self-administration.