Regulation of neurotransmitter enzyme by quisqualate subtype glutamate receptors in cultured cerebellar and hippocampal neurons

The possible involvement of ionotropic and metabotropic quisqualate (QA) receptors in neuronal plasticity was studied in cultured glutamtergic cerebellar or hippocampal cells in terms of the specific activity of phosphate-activated glutaminase, an enzyme important in the synthesis of the putative neurotransmitter pool of glutamate. When cerebellar of hippocampal neurons were treated with QA, it elevated the specific activity of glutaminase in a dose-dependent manner. The half-maximal effect was obtained at about 0.1 μM, the maximum increase was at about 1 μM, but levels higher than 10 μM QA produced progressive reduction in glutaminase activity. In contrast, QA had little effects on the activities of lactate dehydrogenase and aspartate aminotransferase and the amount of protein, indicating that the increase in glutaminase was relatively specific. The QA-mediated increase in glutaminase was mimicked by the ionotropic QA receptor agonist -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; EC₅₀, about 0.5 μM), but not by the metabotropic QA receptor agonist trans-(±)-1-aino-cyclopentyl-1,3,dicarboxyalte (t-ACPD; up to 0.5 mM). The specific ionotropic QA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inhibited QA- and AMPA-mediated increases in glutaminase activity in a dose-dependent manner, whereas other glutamate receptor antagonists, -2-amino-5-phosphonovalerate, γ- -glutamyl aminomethyl sulphonic acid and γ- -glutamyl diethyl ester were ineffective. The elevation of neurotransmitter enzyme was Ca²⁺-dependent. The increase in Ca²⁺ influx essentially through the activation of L-type voltage-operated Ca²⁺ channels, and not the mobilization of internal Ca²⁺ stores, was responsible for these QA receptor-mediated long-term plastic changes in hippocampal and cerebellar neurons.     

Impact of nutrition on muscle mass, strength, and performance in older adults

Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia—the gradual loss of skeletal muscle mass and strength that occurs with advancing age—has recently received increased attention. A review of the literature was undertaken to identify nutritional factors that contribute to loss of muscle mass. The role of protein, acid–base balance, vitamin D/calcium, and other minor nutrients like B vitamins was reviewed. Muscle wasting is a multifactorial process involving intrinsic and extrinsic alterations. A loss of fast twitch fibers, glycation of proteins, and insulin resistance may play an important role in the loss of muscle strength and development of sarcopenia. Protein intake plays an integral part in muscle health and an intake of 1.0–1.2 g/kg of body weight per day is probably optimal for older adults. There is a moderate inverse relationship between vitamin D status and muscle strength. Chronic ingestion of acid-producing diets appears to have a negative impact on muscle performance, and decreases in vitamin B₁₂ and folic acid intake may also impair muscle function through their action on homocysteine. An adequate nutritional intake and an optimal dietary acid–base balance are important elements of any strategy to preserve muscle mass and strength during aging.     

Nuclear gyrB encodes a functional subunit of the Plasmodium falciparum gyrase that is involved in apicoplast DNA replication

The DNA replication machinery of the Plasmodium falciparum apicoplast is a validated drug target. Nuclear-encoded gyrase subunits are predicted to play a critical role in maintaining DNA topology during the D-loop/bi-directional ori replication process of the parasite. We show the presence of P. falciparum gyrase subunits in parasite lysates by using antibodies generated against recombinant gyrase A and B. The ATPase activity of PfGyrB was inhibited by novobiocin that also caused parasite death in culture. Reduction of apicoplast/nuclear DNA ratio in the presence of novobiocin indicated that the drug targets apicoplast DNA replication. Molecular modeling of gyrase A and B subunits revealed extensive fold conservation with the Escherichia coli counterparts as well as the presence of a long disordered loop adjacent to the ATPase domain of PfGyrB. Our results have implications for development of PfGyrB as a drug target against malaria.     

Non-alcoholic fatty liver disease and clinical outcomes in patients with COVID-19: A comprehensive systematic review and meta-analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) patients represent a vulnerable population that may be susceptible to more severe COVID-19. Moreover, not only the underlying NAFLD may influence the progression of COVID-19, but the COVID-19 may affect the clinical course of NAFLD as well. However, comprehensive evidence on clinical outcomes in patients with NAFLD is not well characterized.ObjectivesTo systematically review and meta-analysis the evidence on clinical outcomes in NAFLD patients with COVID-19.MethodsMEDLINE, EMBASE, and Cochrane Central were searched from inception through November 2020. Epidemiological studies assessing the clinical outcomes in COVID-19 patients with NAFLD were included. Newcastle-Ottawa Scale (NOS) was used to assess study quality. Generic inverse variance method using RevMan was used to determine the pooled estimates using the random-effects model.ResultsFourteen studies consisting of 1851 NAFLD patients, were included. Significant heterogeneity was observed among the studies, and studies were of moderate to high quality [mean, (range):8 (6, 8)]. For NAFLD patients, the adjusted odds ratio (aOR) for the severe COVID-19 was 2.60 (95%CI:2.24–3.02; p < 0.001) (studies,n:8), aOR for admission to ICU due to COVID-19 was 1.66 (95%CI:1.26–2.20; p < 0.001) (studies,n:2), and aOR for mortality for was 1.01 (95%CI:0.65–1.58; p = 0.96) (studies,n:2).ConclusionsAn increased risk of severe COVID-19 infection and admission to ICU due to COVID-19 with no difference in mortality was observed between NAFLD and non-NAFLD patients. Future studies should include the mortality outcome to conclusively elucidate the impact of NAFLD in patients with COVID-19.     

Incidence and Risk of Intestinal and Extra-intestinal Complications in Medicaid Patients with Inflammatory Bowel Disease: A 5-Year Population-Based Study

Background and Aim  

Intestinal and extra-intestinal complications are associated with inflammatory bowel disease (IBD) but their exact incidence is not well known. In order to improve our understanding of their incidence and impact, we assessed the complications associated with ulcerative colitis (UC) and Crohn’s disease (CD) in a population-based study in Medicaid patients.