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A concept of physicochemical forms of biologically active substances introduced in investigation of the action mechanism of ultra-low doses allows qualitative explanation of the main effects of ultra-low doses, chemical diversity of biologically active substances, and physical boundaries for these effects. Phenazepam was shown to possess activity in ultra-low doses only in disperse state, in the form of nanoparticles with a diameter <100-300 nm; these nanoparticles appear as micelles of surface active substances and solvated. Panavir possesses pharmacological activity in ultra-low doses and appears as nanoparticles with a diameter of 200-300 nm, which have uncompensated negative surface charge and polymer nature.

This short report is dedicated to the description of the wide antiviral and antibacterial activity of the immunemodulating agent Panavir®. Panavir® is a high-molecular-weight fraction of the polysaccharides extracted from the shoots of the Solanum tuberosum. It demonstrates activity against many types of viruses, including animal coronavirus and also against bacterial infections. These properties look very promising considering the COVID-19 epidemy and allow propose that Panavir® would be effective in the therapy of the SARS-CoV-2 infection.

Adrenal glands are the major organs releasing catecholamines and regulating our stress response. The mechanisms balancing generation of adrenergic chromaffin cells and protecting against neuroblastoma tumors are still enigmatic. Here we revealed that serotonin (5HT) controls the numbers of chromaffin cells by acting upon their immediate progenitor “bridge” cells via 5-hydroxytryptamine receptor 3A (HTR3A), and the aggressive HTR3Ahigh human neuroblastoma cell lines reduce proliferation in response to HTR3A-specific agonists. In embryos (in vivo), the physiological increase of 5HT caused a prolongation of the cell cycle in “bridge” progenitors leading to a smaller chromaffin population and changing the balance of hormones and behavioral patterns in adulthood. These behavioral effects and smaller adrenals were mirrored in the progeny of pregnant female mice subjected to experimental stress, suggesting a maternal-fetal link that controls developmental adaptations. Finally, these results corresponded to a size-distribution of adrenals found in wild rodents with different coping strategies.

The antidepressant-like effect of fluoxetine (20 mg/kg i.p.) has been assessed using the forced swimming test (FST) in IRC (CD-1) mice exposed or not to a pretest session of different duration (5 or 20 min). The influence of the mitochondrial translocator protein (TSPO) activity on the antidepressant-like effect of fluoxetine (20 mg/kg i.p.) in the FST was also studied. The antidepressant-like effect of fluoxetine was observed only in mice subjected to a 5-min pretest session 24 h before the FST. The TSPO antagonist PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; 1 or 3 mg/kg i.p.] inhibited the antidepressant activity of fluoxetine in the FST. In the present study, fluoxetine or PK11195 was administered for a short duration. We suppose that the functional activity of TSPO may depend on a pretest session and that using this procedure is necessary to detect antidepressant activity of fluoxetine-like drugs.

ImportanceThe long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified.ObjectiveTo examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years’ corrected age.Design, Setting, and ParticipantsFollow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years’ corrected age was completed on December 9, 2022.InterventionsInfants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment.Main Outcomes and MeasuresThe key secondary outcome of death or moderate to severe NDD was assessed at 2 years’ corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years.ResultsAmong the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, −7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]).Conclusions and RelevanceIn this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life.Trial Registrationanzctr.org.au Identifier: ACTRN12611000916943

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The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organisms is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacological effects of psychotropic drugs possessing immunomodulatory and/or antiviral properties have shown a correlation between central effects of examined drugs associated with the impact on the processes of neurogenesis of adult brain and survival of neurons, and their ability to alter levels of key proinflammatory cytokines. The changes that occur as a result of the influence of pharmacological agents at one of the systems should inevitably lead to the functional reorganization at another. Integrative mechanisms underlying the neuro-immune interactions may explain the "pleiotropic" pharmacological effects of some antiviral and immunomodulatory drugs. Amantadine, which was originally considered as an antiviral agent, was approved as anti-parkinsonic drug after its wide medical use. The prolonged administration of interferon alpha caused depression in 30-45% of patients, thus limiting its clinical use. The antiviral drug "Oseltamivir" may provoke the development of central side effects, including abnormal behavior, delirium, impaired perception and suicides. Anti-herpethetical drug "Panavir" shows pronounced neuroprotective properties. The purpose of this review is to analyze the experimental and clinical data related to central effects of drugs with antiviral or/and immunotropic activity, and to discover the relationship of these effects with changes in reactivity of immune system and proinflammatory response.