Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways

Recently the two vesicular-glutamate-transporters VGLUT1 and VGLUT2 have been cloned and characterized. VGLUT1 and VGLUT2 together label all glutamatergic neurons, but because of their distinct expression patterns in the brain they facilitate our ability to define between a VGLUT1-positive cortical and a VGLUT2-positive subcortical glutamatergic systems. We have previously demonstrated an increased cortical VGLUT1 expression as marker of antidepressant activity. Here, we assessed the effects of different psychotropic drugs on brain VGLUT2 mRNA and protein expression. The typical antipsychotic haloperidol, and the atypicals clozapine and risperidone increased VGLUT2 mRNA selectively in the central medial/medial parafascicular, paraventricular and intermediodorsal thalamic nuclei; VGLUT2 protein was accordingly amplified in paraventricular and ventral striatum and in prefrontal cortex. The antidepressants fluoxetine and desipramine and the sedative anxiolytic diazepam had no effect. These results highlight the implication of thalamo-limbic glutamatergic pathways in the action of antipsychotics. Increased VGLUT2 expression in these neurons might constitute a marker for antipsychotic activity and subcortical glutamate neurotransmission might be a possible novel target for future generation antipsychotics.     

Bcl-2 decreases cell proliferation and promotes accumulation of cells in S phase without affecting the rate of apoptosis in human ovarian carcinoma cells

OBJECTIVES: The Bcl-2 protein is an important regulator of the apoptotic cascade and promotes cell survival. Bcl-2 can also delay entry into the cell cycle from quiescence. In the present study, we used two isogenic human ovarian carcinoma cell lines, which expressed differential levels of Bcl-2 proteins, to demonstrate that Bcl-2 may regulate the growth rates of adenocarcinoma cells. METHODS: The growth rates of two isogenic ovarian cancer cell lines were determined by XTT assays and flow cytometry combined with PI staining. Bcl-2-overexpressing SKOV3 cells were modified to express a doxycycline-inducible anti-Bcl-2 single-chain antibody and the effects of Bcl-2 protein inhibition on cell proliferation and apoptosis were assessed. RESULTS: We demonstrate that Bcl-2 promotes the accumulation of proliferating carcinoma cells in S phase. The Bcl-2-overexpressing SKOV3 cell line proliferates markedly faster and shows delayed progression to G2M phase compared to its low Bcl-2-expressing counterpart SKOV3.ip1 cell line. Single-chain antibody-mediated inhibition of Bcl-2 in SKOV3 cells was associated with increased growth rates and more rapid cell cycle progression. Treatment with cisplatin resulted in more cells accumulating in S phase in Bcl-2-overexpressing SKOV3 cells, while the inhibition of Bcl-2 abolished delayed entry into G2M phase without affecting cisplatin-induced apoptosis. CONCLUSIONS: Our results suggest that, in ovarian cancer cells, Bcl-2 delays cell cycle progression by promoting accumulation of cells in S phase without affecting the rate of apoptosis. Thus, in addition to its known role at the G0/G1 checkpoint, we demonstrate for the first time that Bcl-2 also regulates the S phase.     

Evaluation of Rapid Lateral-Flow Tests Directed against the SARS-CoV-2 Nucleoprotein Using Viral Suspensions Belonging to Different Lineages of SARS-CoV-2

Within the successive waves that occurred during the SARS-CoV-2 pandemic, recommendations arose to test symptomatic and contact subjects by using rapid antigen devices directed against the viral nucleocapsid protein with the aim to isolate contagious patients without delay. The objective of this study was to evaluate the ability of four rapid lateral-flow tests (RLFT) that were commercially available on the French market in 2022 to recognize various strains of SARS-CoV-2. Series of five-fold dilutions of seven viral suspensions belonging to different lineages of SARS-CoV-2 (19A, 20A, Alpha, Beta, Gamma, Delta and Omicron) were used to evaluate the analytical sensitivity of four commercially available RLFTs (manufacturers: Abbott, AAZ, Becton-Dickinson and Biospeedia). Cell culture and quantitative RT-PCR were used as references. Excellent correlations were observed for each lineage strain between the viral titer obtained via cell culture and the number of RNA copies measured by quantitative RT-PCR. Although the four tests were able to recognize all the tested variants, significant differences in terms of sensitivity were observed between the four RLFTs. Despite the limitation represented by the small number of devices and clinical isolates that were tested, this study contributed by rapidly comparing the sensitivity of SARS-CoV-2 RLFTs in the Omicron era.     

Impact of Dextran-Sodium-Sulfate-Induced Enteritis on Murine Cytomegalovirus Reactivation

(1) Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the intestines, which participates in human cytomegalovirus (HCMV) reactivation from its latent reservoir. CMV-associated colitis plays a pejorative role in the clinical course of UC. We took advantage of a model of chemically induced enteritis to study the viral reactivation of murine CMV (MCMV) in the context of gut inflammation. (2) Methods: Seven-week-old BALB/c mice were infected by 3 × 10³ plaque-forming units (PFU) of MCMV; 2.5% (w/v) DSS was administered in the drinking water from day (D) 30 to D37 post-infection to induce enteritis. (3) Results: MCMV DNA levels in the circulation decreased from D21 after infection until resolution of the acute infection. DSS administration resulted in weight loss, high disease activity index, elevated Nancy index shortening of the colon length and increase in fecal lipocalin. However, chemically induced enteritis had no impact on MCMV reactivation as determined by qPCR and immunohistochemistry of intestinal tissues. (4) Conclusions: Despite the persistence of MCMV in the digestive tissues after the acute phase of infection, the gut inflammation induced by DSS did not induce MCMV reactivation in intestinal tissues, thus failing to recapitulate inflammation-driven HCMV reactivation in human UC.     

One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.     

Improving outcomes of acute myocarditis in children

Acute viral myocarditis may impair prognosis in children of all ages. Its true incidence is underestimated because of heterogeneity of presentation and outcome. Patients may either recover or progress to chronic cardiomyopathy or death. Improving short-term and long-term prognosis is challenging but can probably be achieved by new diagnostic techniques and novel targeted therapies. The objectives of this review are: (1) to detail the current state of knowledge of the pathophysiological mechanisms of acute myocarditis; (2) to provide an update on diagnostic tools such as magnetic resonance imaging and endomyocardial biopsy; and (3) to present new insights in therapeutic strategies, targeted therapies and management of fulminant cases. Options for improving outcomes in acute myocarditis in the pediatric population are discussed.