Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new pandemic infectious disease that originated in China. COVID-19 is a global public health emergency of international concern. COVID-19 causes mild to severe illness with high morbidity and mortality, especially in preexisting risk groups. Therapeutic options are now limited to COVID-19. The hallmark of COVID-19 pathogenesis is the cytokine storm with elevated levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-alpha (TNF-α), chemokine (C-C-motif) ligand 2 (CCL2), and granulocyte-macrophage colony-stimulating factor (GM-CSF). COVID-19 can cause severe pneumonia, and neurological disorders, including stroke, the damage to the neurovascular unit, blood-brain barrier disruption, high intracranial proinflammatory cytokines, and endothelial cell damage in the brain. Mast cells are innate immune cells and also implicated in adaptive immune response, systemic inflammatory diseases, neuroinflammatory diseases, traumatic brain injury and stroke, and stress disorders. SARS-CoV-2 can activate monocytes/macrophages, dendritic cells, T cells, mast cells, neutrophils, and induce cytokine storm in the lung. COVID-19 can activate mast cells, neurons, glial cells, and endothelial cells. SARS-CoV-2 infection can cause psychological stress and neuroinflammation. In conclusion, COVID-19 can induce mast cell activation, psychological stress, cytokine storm, and neuroinflammation.

SYSNOPSISThirty drug-free patients suffering from chronic anxiety states were compared with 30 normal controls matched for age, sex, and social class on a variety of physiological and psychological measures. The tests included the electroencephalogram, the auditory evoked response, and skin conductance recorded during a passive and an active condition and auditory reaction time, the digit symbol substitution test, and arithmetic. The patients showed increased EEG voltage, shorter latencies of the evoked response, higher skin conductance levels, higher pulse rate and less pupillary constriction, and they responded less to the increase in activation. They also showed impairment on complex psychological tests. It is concluded that pathological anxiety involves an increase in arousal irrelevant to the task and has a disorganizing rather than a facilitating effect on performance.

Acute traumatic brain injury (TBI) leads to neuroinflammation, neurodegeneration, cognitive decline, psychological disorders, increased blood-brain barrier (BBB) permeability, and microvascular damage in the brain. Inflammatory mediators secreted from activated glial cells, neurons, and mast cells are implicated in the pathogenesis of TBI through secondary brain damage. Abnormalities or damage to the neurovascular unit is the indication of secondary injuries in the brain after TBI. However, the precise mechanisms of molecular and ultrastructural neurovascular alterations involved in the pathogenesis of acute TBI are not yet clearly understood. Moreover, currently, there are no precision-targeted effective treatment options to prevent the sequelae of TBI. In this study, mice were subjected to closed head weight-drop-induced acute TBI and evaluated neuroinflammatory and neurovascular alterations in the brain by immunofluorescence staining or quantitation by enzyme-linked immunosorbent assay (ELISA) procedure. Mast cell stabilizer drug cromolyn was administered to inhibit the neuroinflammatory response of TBI. Results indicate decreased level of pericyte marker platelet-derived growth factor receptor-beta (PDGFR-β) and BBB-associated tight junction proteins junctional adhesion molecule-A (JAM-A) and zonula occludens-1 (ZO-1) in the brains 7 days after weight-drop-induced acute TBI as compared with the brains from sham control mice indicating acute TBI-associated BBB/ tight junction protein disruption. Further, the administration of cromolyn drug significantly inhibited acute TBI-associated decrease of PDGFR-β, JAM-A, and ZO-1 in the brain. These findings suggest that acute TBI causes BBB/tight junction damage and that cromolyn administration could protect this acute TBI-induced brain damage as well as its long-time consequences.

SYSNOPSISTwenty outpatients with chronic anxiety states were tested on a large battery of physiological and psychological tests after amylobarbitone sodium, chlordiazepoxide, diazepam, and medazepam given in flexible dosage and compared with a placebo. Each patient received all five treatments for two to four weeks under double-blind conditions, as part of a fully balanced design. The tests included the electroencephalogram, the auditory evoked response, skin conductance, the Digit Symbol Substitution Test, the Gibson Spiral Maze, and arithmetic tests, together with psychiatrist and patient ratings. Correlations within and between the different measures were computed. The benzodiazepines depressed slow wave and increased fast wave activity of the EEG, diminished the evoked response, reduced fluctuations in the skin conductance, and decreased motor speed on the Gibson Maze. Amylobarbitone had less physiological effect but impaired performance on the Gibson Maze and arithmetic tests. Significant correlations were found between the mean Hamilton and patient ratings and the physiological measures. It is concluded that physiological changes show useful correlations with clinical effects.

SYSNOPSISTwenty outpatients suffering from chronic anxiety states completed a trial of anxiolytic drug therapy. They each received five treatments: amylobarbitone sodium, chlordiazepoxide, diazepam, medazepam, and a placebo in flexible dosage in a fully balanced design, using doubleblind procedures. They were assessed on the Hamilton rating scale for anxiety after a period of two to four weeks on each of the treatments and they completed self-ratings every three days. The selfratings were composed of at least three prime symptoms chosen by the patient himself and phrased in his own words as well as ‘loss of appetite’ and ‘insomnia’. Neither placebo nor amylobarbitone produced any substantial improvement from pre-drug levels of anxiety but all three benzodiazepines produced significant and very similar decreases in both Hamilton ratings and self-ratings. These two measures also correlated highly. The majority of the patients continued with medazepam at the end of the formal trial.