Ethanol upregulates the P2X7 purinergic receptor in human macrophages

Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome and are involved in many ethanol‐related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis, and certain cancers). We hypothesized that ethanol regulates purinergic receptors and thus modulates the NLRP3 inflammasome's activity. In experiments with monocyte‐derived macrophages, we found that interleukin (IL)‐1β secretion was inhibited after 7 h of exposure (but not 48 h of exposure) to ethanol. The disappearance of ethanol's inhibitory effect on IL‐1β secretion after 48 h was not mediated by the upregulated production of IL‐1β, IL‐1α, IL‐6 or the inflammasome components NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain, and caspase 1. P2X7R expression was upregulated by ethanol, whereas expression of the P2X4 and P2X1 receptors was not. Taken as a whole, our results suggest that ethanol induces NLRP3 inflammasome activation by upregulating the P2X7 receptor. This observation might have revealed a new mechanism for inflammation in ethanol‐related diseases.     

Correction to: Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

European Journal of Clinical Microbiology & Infectious Diseases -     

Risk for Hepatitis E Virus Transmission by Solvent/Detergent–Treated Plasma

Hepatitis E has emerged as a major transfusion-transmitted infectious risk. Two recipients of plasma from 2 lots (A and B) of pooled solvent/detergent–treated plasma were found to be infected by hepatitis E virus (HEV) that was determined to have been transmitted by the solvent/detergent–treated plasma. HEV RNA viral loads were 433 IU in lot A and 55 IU in lot B. Retrospective studies found that 100% (13/13) of evaluable lot A recipients versus 18% (3/17) of evaluable lot B recipients had been infected by HEV (p<0.001), albeit not necessarily at time of transfusion. Among evaluable recipients, 86% with a transfused HEV RNA load >50,000 IU were infected, most likely by the HEV-containing solvent/detergent–treated plasma, versus only 7% with a transfused HEV RNA load <50,000 IU (p<0.001). Overall, solvent/detergent–treated plasma might harbor HEV. Such an occurrence might result in a dose-dependent risk for transfusion-transmitted hepatitis E.     

Hidden administration of 5-APB in a dancing club of New Caledonia documented by urine analysis: about 3 cases

1-Benzofuran-5-ylpropan-2-amine or 5-APB is a new psychoactive substance (NPS) with empathic effects close to ecstasy (MDMA). Although 5-APB has been observed in fatality cases, the drug has not yet been reported in the context of hidden administration for behaviour impairment, also known as drug-facilitated crime. Such a situation was recently observed on 3 separate occasions in the same dancing club of New Caledonia. It involves 3 women, aged 27, 29, and 33 years who presented, after having drunk a cocktail, anxiety, abnormal movements of the inferior jaw, and aggressiveness. No memory loss was noticed. About 12 h after the event, a urine specimen was collected in the 3 cases. Comprehensive toxicology was requested and only 5-APB was identified, at 6, 8, and 14 ng/mL. Urine ethanol tested negative, which is consistent with the limited intake before the event occurred. These results have demonstrated that NPS are circulating in New Caledonia, which was not previously reported, and that 5-APB, like ecstasy, can be used to modify the behaviour of a subject, as it can be done by a chemical weapon.

     

Glutamate transporter 1-expressing glia in the rat substantia nigra—Morphometric analysis and relationships to synapses

Glial cells have a major role in protecting neurons against various forms of stress. Especially, astrocytes mediate the bulk of glutamate clearance in the brain via specific membrane transporters (GLAST and GLT1), thereby preventing the occurrence of excitotoxic events. Although glutamate-mediated mechanisms are thought to contribute to nigral dopaminergic neuron degeneration in Parkinson's disease, detailed information on the organization of glia in the substantia nigra is still lacking. The present study was performed to provide quantitative information on the organization of astroglia and on the relationships between astrocytes and excitatory synapses in the rat substantia nigra. Using immunolabeling of GLT1 and confocal imaging, we found that the substantia nigra was filled with a dense meshwork of immunoreactive astrocyte processes. Stereological analysis performed on electron microscope images revealed that the density of immunoreactive astrocyte plasma membranes was substantial, close to 1 μm²/μm³, in the substantia nigra neuropil, both in the pars compacta and the pars reticulata. Excitatory synapses had on average two thirds of their perimeters free from glia, a disposition that may favor transmitter spillover. The density of glutamatergic synapses, as quantified on confocal images by the simultaneous detection of bassoon and of vesicular glutamate transporter 1 or 2, was very low (0.01 and 0.025 per μm³ in the reticulata and compacta subdivisions, respectively). Thus the ratio of GLT1-expressing glial membrane surface to glutamatergic synapses was very high (40–100 μm²), suggesting an efficient regulation of extracellular glutamate concentrations.     

Allogeneic hematopoietic stem cell transplantation for T‐prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM‐TC)

T‐prolymphocytic leukemia (T‐PLL), a rare aggressive mature T‐cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly serve to consolidate the response to initial chemotherapy. The current report summarizes the outcome of 27 T‐PLL cases identified in the registry in French Society for stem cell transplantation (SFGM‐TC). Prior to HSCT, 14 patients were in complete remission (CR), 10 in partial response, three refractory, or in progression. Following HSCT, 21 patients achieved CR as best response. With a median follow‐up for surviving patients of 33 (range, 6–103) months, 10 patients are still alive in continuous CR. Overall survival and progression‐free survival estimates at 3 yr were 36% (95% CI: 17–54%) and 26% (95% CI: 14–45%), respectively. The relapse incidence after HSCT was 47% occurring at a median of 11.7 (range, 2–24) months. Overall cumulative incidence of transplant‐related mortality was 31% at 3 yr. These results suggest that HSCT may allow long‐term survival in patients with T‐PLL following induction treatment; however, it is associated with a significant rate of toxicity.