Listeria monocytogenes meningoencephalitis against the background of the new coronavirus infection: a clinical case

Background: Among the bacteria that affect the central nervous system, Listeria monocytogenes (facultative intracellular bacterium) is one of the most lethal to humans and animals. Listeriosis affects domestic and farm animals (pigs, small and large cattle, horses, rabbits, less often cats and dogs), as well as domestic and ornamental birds (geese, chickens, ducks, turkeys, pigeons, parrots and canaries). L. monocytogenes can be detected in fish and seafood (shrimp). The source of L. monocytogenes infection are animals in which the disease may manifest itself or occur in erased and asymptomatic forms followed by the transition to a long-term carriage. This pathogen is found throughout the world in foodstuffs, and most cases of infection occur through the ingestion of contaminated food. Particularly susceptible to the disease are embryos, newborns, the elderly and individuals with immunodeficiencies and chronic diseases. L. monocytogenes can cause intracranial hemorrhage, meningitis, meningoencephalitis, and rhombencephalitis. Clinical case description: This paper presents our own clinical observation of the development of severe listeriosis meningoencephalitis in a 47 year-old patient against the background of the new coronavirus infection (COVID-19). We describe the details of the clinical presentation, the treatment and the favorable outcome in our patient. Conclusion: Invasive listeriosis is a rare disease. The knowledge about the clinical manifestations of this disease is needed not only for epidemiologists and infectious disease specialists, but also for physicians of other specialties. Untimely diagnosis and inadequate antibacterial therapy are dangerous leading to severe somatic and neurological complications with a lethal outcome or disability both in children and adult persons

Dysregulation of Ca2+ signaling in astrocytes from mice lacking amyloid precursor protein

The relationship between altered metabolism of the amyloid-β precursor protein (APP) and Alzheimer's disease is well established but the physiological roles of APP still remain unclear. Here, we studied Ca2+ signaling in primary cultured and freshly dissociated cortical astrocytes from APP knockout (KO) mice and from Tg5469 mice overproducing by five- to sixfold wild-type APP. Resting cytosolic Ca2+ (measured with fura-2) was not altered in cultured astrocytes from APP KO mice. The stored Ca2+ evaluated by measuring peak amplitude of cyclopiazonic acid [CPA, endoplasmic reticulum (ER) Ca2+ ATPase inhibitor]-induced Ca2+ transients in Ca2+-free medium was significantly smaller in APP KO astrocytes than in wild-type cells. Store-operated Ca2+ entry (SOCE) activated by ER Ca2+ store depletion with CPA was also greatly reduced in APP KO astrocytes. This reflected a downregulated expression in APP KO astrocytes of TRPC1 (C-type transient receptor potential) and Orai1 proteins, essential components of store-operated channels (SOCs). Indeed, silencer RNA (siRNA) knockdown of Orai1 protein expression in wild-type astrocytes significantly attenuated SOCE. SOCE was also essentially reduced in freshly dissociated APP KO astrocytes. Importantly, knockdown of APP with siRNA in cultured wild-type astrocytes markedly attenuated ATP- and CPA-induced ER Ca2+ release and extracellular Ca2+ influx. The latter correlated with downregulation of TRPC1. Overproduction of APP in Tg5469 mice did not alter, however, the stored Ca2+ level, SOCE, and expression of TRPC1/4/5 in cultured astrocytes from these mice. The data demonstrate that the functional role of APP in astrocytes involves the regulation of TRPC1/Orai1-encoded SOCs critical for Ca2+ signaling

Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture

Phenotypic modulation of vascular myocytes is important for vascular development and adaptation. A characteristic feature of this process is alteration in intracellular Ca2+ handling, which is not completely understood. We studied mechanisms involved in functional changes of inositol 1,4,5-trisphosphate (IP3)- and ryanodine (Ry)-sensitive Ca2+ stores, store-operated Ca2+ entry (SOCE), and receptor-operated Ca2+ entry (ROCE) associated with arterial myocyte modulation from a contractile to a proliferative phenotype in culture. Proliferating, cultured myocytes from rat mesenteric artery have elevated resting cytosolic Ca2+ levels and increased IP3-sensitive Ca2+ store content. ATP- and cyclopiazonic acid [CPA; a sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) inhibitor]-induced Ca2+ transients in Ca2+-free medium are significantly larger in proliferating arterial smooth muscle cells (ASMCs) than in freshly dissociated myocytes, whereas caffeine (Caf)-induced Ca2+ release is much smaller. Moreover, the Caf/Ry-sensitive store gradually loses sensitivity to Caf activation during cell culture. These changes can be explained by increased expression of all three IP3 receptors and a switch from Ry receptor type II to type III expression during proliferation. SOCE, activated by depletion of the IP3/CPA-sensitive store, is greatly increased in proliferating ASMCs. Augmented SOCE and ROCE (activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol) in proliferating myocytes can be attributed to upregulated expression of, respectively, transient receptor potential proteins TRPC1/4/5 and TRPC3/6. Moreover, stromal interacting molecule 1 (STIM1) and Orai proteins are upregulated in proliferating cells. Increased expression of IP3 receptors, SERCA2b, TRPCs, Orai(s), and STIM1 in proliferating ASMCs suggests that these proteins play a critical role in an altered Ca2+ handling that occurs during vascular growth and remodeling

Activation of c-SRC underlies the differential effects of ouabain and digoxin on Ca2+ signaling in arterial smooth muscle cells

Cardiotonic steroids (CTS) of the strophanthus and digitalis families have opposing effects on long-term blood pressure (BP). This implies hitherto unrecognized divergent signaling pathways for these CTS. Prolonged ouabain treatment upregulates Ca(2+) entry via Na(+)/Ca(2+) exchanger-1 (NCX1) and TRPC6 gene-encoded receptor-operated channels in mesenteric artery smooth muscle cells (ASMCs) in vivo and in vitro. Here, we test the effects of digoxin on Ca(2+) entry and signaling in ASMC. In contrast to ouabain treatment, the in vivo administration of digoxin (30 μg·kg(−1)·day(−1) for 3 wk) did not raise BP and had no effect on resting cytolic free Ca(2+) concentration ([Ca(2+)](cyt)) or phenylephrine-induced Ca(2+) signals in isolated ASMCs. Expression of transporters in the α2 Na(+) pump-NCX1-TRPC6 Ca(2+) signaling pathway was not altered in arteries from digoxin-treated rats. Upregulated α2 Na(+) pumps and a phosphorylated form of the c-SRC protein kinase (pY419-Src, ∼4.5-fold) were observed in ASMCs from rats treated with ouabain but not digoxin. Moreover, in primary cultured ASMCs from normal rats, treatment with digoxin (100 nM, 72 h) did not upregulate NCX1 and TRPC6 but blocked the ouabain-induced upregulation of these transporters. Pretreatment of ASMCs with the c-Src inhibitor PP2 (1 μM; 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) but not its inactive analog eliminated the effect of ouabain on NCX1 and TRPC6 expression and ATP-induced Ca(2+) entry. Thus, in contrast to ouabain, the interaction of digoxin with α2 Na(+) pumps is unable to activate c-Src phosphorylation and upregulate the downstream NCX1-TRPC6 Ca(2+) signaling pathway in ASMCs. The inability of digoxin to upregulate c-Src may underlie its inability to raise long-term BP