Synthesis and Anti-influenza A Virus Activity of 2,2-Dialkylamantadines and Related Compounds

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Significant finding of Bordetella holmesii DNA in nasopharyngeal samples from French patients with suspected pertussis

Pertussis is routinely diagnosed with real-time PCR based on insertion sequence IS481, which is not specific for Bordetella pertussis. We conducted a retrospective study using real-time PCRs specific for Bordetella pertussis and for Bordetella holmesii on 177 samples positive for IS481 PCR. Bordetella holmesii DNA was detected in 20.3% samples collected from adolescents and adults.     

Gavage-related reflux in rats: identification, pathogenesis, and toxicological implications (review)

After oral gavage dosing of rats, reflux may occur, resulting in serious respiratory effects and mortality. Published information on gavage-related reflux is limited, as it has not yet been a focus of research. Nevertheless, it represents a recurrent challenge in daily toxicology practice of oral gavage dosing. The absence of clear guidance and criteria for the identification and management of reflux-induced effects can limit the ability to properly interpret toxicity study results. The review presented herein includes an overview of experimental data from gavage studies in rats, in which reflux was observed, and provides a comprehensive analysis of the literature on reflux in general and the different potential pathways contributing to gavage-related reflux in rats. The article aims to increase the awareness and understanding of the pathogenesis of gavage-related reflux and provides guidance on identification of potential risk factors, as well as interpretation of histological changes and their toxicological relevance. Furthermore, differentiation of reflux-induced effects from direct compound-related toxicity and from gavage errors is addressed in particular, and the importance of nasal histology is discussed.     

Unexpected nasal changes in rats related to reflux after gavage dosing

In a three-week oral gavage toxicity study in rats, a high incidence of respiratory symptoms and high mortality was noted in compound-dosed rats only. Because of audible respiration, an effect in the upper respiratory tract was suspected and the nasal cavity was included for examination. Histology revealed extensive necrosis and purulent inflammation within the nasal passages, indicative of direct irritation. Since posterior nasal regions were most affected, with food material present within the inflammatory exudates, reflux and retrograde aspiration of irritant material (possibly stomach contents with test formulation) into the nasal cavity were suspected. Lowering the dose volume and fasting the rats prior to gavage dosing substantially reduced the respiratory effects and mortality. The current article focuses on the histological changes in the nasal cavity indicative of gavage-related reflux and provides guidance on differentiation between technical gavage error and gavage-related reflux.     

Accuracy of the API Campy system,the Vitek 2 Neisseria–Haemophilus card and matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the identification of Campylobacter and related organisms

Biochemical identification of Campylobacter and related organisms is not always specific, and may lead to diagnostic errors. The API Campy, the Vitek 2 system and matrix-assisted desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) are commercially available methods that are routinely used for the identification of these microorganisms. In the present study, we used 224 clinical isolates and ten reference strains previously identified by multiple PCR assays, whole cell protein profiling and either DNA–DNA hybridization or sequencing analysis to compare the reliability of these three methods for the identification of Campylobacter and related pathogens. The API Campy accurately identified 94.4% of Campylobacter jejuni ssp. jejuni and 73.8% of Campylobacter coli, but failed to correctly identify 52.3% of other Epsilobacteria. The Vitek 2 Neisseria–Haemophilus card correctly identified most C. jejuni ssp. jejuni (89.6%) and C. coli (87.7%) strains, which account for the majority of campylobacterioses reported in humans, but it failed in the identification of all of the other species. Despite a good identification rate for both C. jejuni ssp. jejuni and C. coli, both methods showed poor sensitivity in the identification of related organisms, and additional tests were frequently needed. In contrast to API Campy and Vitek, MALDI-TOF MS correctly identified 100% of C. coli and C. jejuni strains tested. With an overall sensitivity of 98.3% and a short response time, this technology appears to be a reliable and promising method for the routine identification of Campylobacter and other Epsilobacteria.     

The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat

It is becoming increasingly apparent that probiotics are important to the health of the host. The absence of probiotic bacteria in the gut can have adverse effects not only locally in the gut, but has also been shown to affect central HPA and monoaminergic activity, features that have been implicated in the aetiology of depression. To evaluate the potential antidepressant properties of probiotics, we tested rats chronically treated with Bifidobacteria infantis in the forced swim test, and also assessed the effects on immune, neuroendocrine and central monoaminergic activity. Sprague-Dawley rats were treated for 14 days with B. infantis. Probiotic administration in naive rats had no effect on swim behaviours on day 3 or day 14 following the commencement of treatment. However, there was a significant attenuation of IFN-γ, TNF-α and IL-6 cytokines following mitogen stimulation (p < 0.05) in probiotic-treated rats relative to controls. Furthermore, there was a marked increase in plasma concentrations of tryptophan (p < 0.005) and kynurenic acid (p < 0.05) in the bifidobacteria-treated rats when compared to controls. Bifidobacteria treatment also resulted in a reduced 5-HIAA concentration in the frontal cortex and a decrease in DOPAC in the amygdaloid cortex. The attenuation of pro-inflammatory immune responses, and the elevation of the serotonergic precursor, tryptophan by bifidobacteria treatment, provides encouraging evidence in support of the proposition that this probiotic may possess antidepressant properties. However, these findings are preliminary and further investigation into the precise mechanisms involved, is warranted.     

Diffusion weighted callosal integrity reflects interhemispheric communication efficiency in multiple sclerosis

We aimed to investigate the relation between damage in the corpus callosum and the performance on an interhemispheric communication task in patients with multiple sclerosis (MS). Relative callosal lesion load defined as the ratio between callosal area and the total lesion load in the total corpus callosum, and the diffusion tensor imaging (DTI) derived measures fractional anisotropy (FA) and transverse and longitudinal diffusivity were calculated in sixteen female MS patients and sixteen age and education matched female controls. The redundancy gain task was used to behaviorally evaluate interhemispheric communication efficiency. During this task, simple reaction times to uni- and bilateral presented stimuli are recorded. The advantage in reaction time for bilateral as compared to unilateral trials, the redundancy gain, was significantly larger for the MS-group. The DTI data showed significantly decreased FA and increased diffusivity parameters in the corpus callosum for the MS patients compared with the control group. Moreover, we found a significant correlation between the DTI-derived measures in the corpus callosum and the redundancy gain effect. Callosal damage in MS, as measured by DTI and defined as transverse diffusivity, is associated with alterations in a behavioral task that relies on interhemispheric transfer and communication.     

Epilepsy as part of the phenotype associated with ATP1A2 mutations

PURPOSE: Mutations in the ATP1A2 gene have been described in families with familial hemiplegic migraine (FHM). FHM is a variant of migraine with aura characterized by the occurrence of hemiplegia during the aura. Within several FHM families, some patients also had epileptic seizures. In this study we tested the hypothesis that mutations in ATP1A2 may be common in patients presenting with epilepsy and migraine. METHODS: We selected 20 families with epilepsy and migraine and performed mutation analysis of ATP1A2 in the probands by direct sequencing of all exons and splice-site junctions. RESULTS: Novel ATP1A2 mutations were found in two of the 20 families (10%). The p.Gly900Arg mutation was present in a family with epilepsy and FHM, and the p.Cys702Tyr mutation occurred in a family with occipitotemporal epilepsy and migraine with and without visual aura. In the two families together, six mutation carriers had the combination of epilepsy and migraine, two had only epilepsy, and six had only migraine. DISCUSSION: This study shows that a history of migraine and a family history of both epilepsy and migraine should be obtained in all patients presenting with epilepsy in the epilepsy clinic. It may be worthwhile to screen patients with a combination of epilepsy and migraine and a positive family history of either migraine or epilepsy for mutations in the ATP1A2 gene.