ABSTRACT
We forecast 1,000,000 COVID-19 cases outside of China by March 31st, 2020 based on a heuristic and WHO situation reports. We do not model the COVID-19 pandemic; we model only the number of cases. The proposed heuristic is based on a simple observation that the plot of the given data is well approximated by an exponential curve. The exponential curve is used for forecasting the growth of new cases. It has been tested for the last situation report of the last day. Its accuracy has been 1.29% for the last day added and predicted by the 57 previous WHO situation reports (the date 18 March 2020). Prediction, forecast, pandemic, COVID-19, coronavirus, exponential growth curve parameter, heuristic, epidemiology, extrapolation, abductive reasoning, WHO situation report.
ABSTRACT
Experiments on random-bred albino mice showed that NF-κB inhibitor (BAY 11-7082) and ß2-adrenoreceptor agonist (dexmedetomidine hydrochloride) significantly reduced mouse mortality in 4 and 24 h after sepsis modeling (intraperitoneal administration of E. coli) by reducing blood levels of proinflammatory cytokines TNFα, IL-1ß, and IL-6. The combined administration of NF-κB inhibitor and ß2-adrenoreceptors agonist have an additive effect.
Subject(s)
Adrenergic beta-Agonists/therapeutic use , Cytokines/metabolism , Dexmedetomidine/therapeutic use , NF-kappa B/antagonists & inhibitors , Nitriles/therapeutic use , Sepsis/drug therapy , Sulfones/therapeutic use , Animals , Female , Male , Mice , Sepsis/metabolism , Sepsis/mortality , Signal Transduction/drug effectsABSTRACT
Experiments on random-bred albino mice showed that of ß2-adrenoreceptor agonist hexaprenaline sulfate significantly reduced mortality of mice from experimental sepsis (intraperitoneal administration of E. coli) in 4 and 24 h after modeling by reducing blood levels of proinflammatory cytokines TNFα, IL-1ß, and IL-6. The antagonist of ß2AR ICI-118,551 eliminated this effect.
Subject(s)
Adrenergic beta-2 Receptor Agonists/pharmacology , Anti-Inflammatory Agents/pharmacology , Escherichia coli Infections/drug therapy , Hexoprenaline/pharmacology , Receptors, Adrenergic, beta-2/metabolism , Sepsis/drug therapy , Adrenergic beta-2 Receptor Antagonists/pharmacology , Animals , Animals, Outbred Strains , Escherichia coli/pathogenicity , Escherichia coli/physiology , Escherichia coli Infections/immunology , Escherichia coli Infections/metabolism , Female , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/biosynthesis , Interleukin-6/antagonists & inhibitors , Interleukin-6/biosynthesis , Male , Mice , Propanolamines/pharmacology , Sepsis/immunology , Sepsis/metabolism , Sepsis/microbiology , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
Experiments on random-bred albino mice showed that M1 muscarinic acetylcholine receptor agonist (TBPB) and α7n-acetylcholine receptor agonist (GTS-21) significantly reduced mortality of mice with experimental sepsis (intraperitoneally administration of E. coli) in 4 and 24 h after modeling by reducing blood concentration of proinflammatory cytokines TNF-α, IL-1ß, and IL-6. Combined treatment with TBPB and GTS-21 determined their additive effect.
Subject(s)
Benzimidazoles/pharmacology , Benzylidene Compounds/pharmacology , Escherichia coli Infections/drug therapy , Muscarinic Agonists/pharmacology , Nicotinic Agonists/pharmacology , Piperidines/pharmacology , Pyridines/pharmacology , Sepsis/drug therapy , Animals , Drug Therapy, Combination , Escherichia coli/pathogenicity , Escherichia coli/physiology , Escherichia coli Infections/microbiology , Escherichia coli Infections/mortality , Escherichia coli Infections/pathology , Female , Gene Expression Regulation , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/blood , Interleukin-6/antagonists & inhibitors , Interleukin-6/blood , Male , Mice , Receptor, Muscarinic M1/agonists , Receptor, Muscarinic M1/genetics , Receptor, Muscarinic M1/metabolism , Sepsis/microbiology , Sepsis/mortality , Sepsis/pathology , Survival Analysis , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/blood , alpha7 Nicotinic Acetylcholine Receptor/agonists , alpha7 Nicotinic Acetylcholine Receptor/genetics , alpha7 Nicotinic Acetylcholine Receptor/metabolismABSTRACT
Experiments on white non-inbred rats demonstrated that treatment with organophosphorus compound dimethyl dichlorovinyl phosphate (DDVP) decreased T cell-independent antibody production by B cells and blood levels of IL-10 and IL-12; a similar effect was produced by GTS-21, a selective agonist of α7-nicotinic acetylcholine receptor. N-nicotinic receptor antagonist chlorisondamine in combination with DDVP partially prevented suppression of antibody production in comparison with the effect observed during intoxication with DDVP.
Subject(s)
B-Lymphocytes/drug effects , Chlorisondamine/pharmacology , Cholinesterase Inhibitors/toxicity , Dichlorvos/toxicity , Nicotinic Antagonists/pharmacology , alpha7 Nicotinic Acetylcholine Receptor/immunology , Animals , Animals, Outbred Strains , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Benzylidene Compounds/pharmacology , Cholinesterase Inhibitors/immunology , Dichlorvos/antagonists & inhibitors , Dichlorvos/immunology , Female , Immunoglobulin M/biosynthesis , Injections, Intramuscular , Interleukin-10/biosynthesis , Interleukin-10/metabolism , Interleukin-12/biosynthesis , Interleukin-12/metabolism , Male , Nicotinic Agonists/pharmacology , Pyridines/pharmacology , Rats , Spleen/cytology , Spleen/drug effects , Spleen/immunology , alpha7 Nicotinic Acetylcholine Receptor/metabolismABSTRACT
It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p < 0.05), and did not affect the content of anti-inflammatory cytokines (IL-10, IL-13). Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.
Subject(s)
Antidotes/pharmacology , Methanol/antagonists & inhibitors , Methanol/poisoning , Pyrazoles/pharmacology , Th1 Cells/drug effects , Th2 Cells/drug effects , Acute Disease , Animals , Animals, Outbred Strains , Female , Fomepizole , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Interferon-gamma/blood , Interleukin-1beta/blood , Interleukin-2/blood , Interleukin-4/blood , Interleukin-6/blood , Male , Methanol/blood , Methanol/immunology , Rats , Th1 Cells/immunology , Th1 Cells/pathology , Th1-Th2 Balance/drug effects , Th2 Cells/immunology , Th2 Cells/pathology , Tumor Necrosis Factor-alpha/bloodABSTRACT
It was established in experiments on noninbred albino rats that acute intoxication with malathion (0.75 LD50) reduced the function of Th1 cells more significantly than the function of Th2 lymphocyte, decreases the activity of B cells and NK cells, blood levels of TNFa, IL-1b and IL-6, IFN-g, IL-2, and IL-4, while not significantly affecting the concentration of IL-10 and IL-13. Atropine (10 mg/kg) under conditions of acute malathion intoxication improved the function of T cells and B lymphocytes, NK cells, as well as the synthesis of immunoregulatory cytokines IFN-g, IL-2, and IL-4. At the same time, atropine in malathion intoxicated rats had no effect on suppression of the synthesis of proinflammatory cytokines TNF, IL-1g and IL-6 as well as the content of anti-inflammatory cytokines IL-10 and IL-13.
Subject(s)
Atropine/pharmacology , Cytokines/immunology , Insecticides/adverse effects , Malathion/adverse effects , Parasympatholytics/administration & dosage , Th2 Cells/immunology , Animals , Female , Insecticides/pharmacology , Malathion/pharmacology , Male , Rats , Th2 Cells/pathologyABSTRACT
Experiments on random-bred albino mice showed that activation α7n-acetylcholine receptors with anabasine (0.5 LD50) and the use of antibodies to TNF-α (1 mg/kg) 2 h before sepsis modeling significantly reduces mortality of mice from experimental sepsis (intraperitoneal injection of E. coli) due to a decrease in the blood concentration of proinflammatory cytokines TNF-α, IL-1ß, and IL-6. After combined administration of anti-TNF-α antibodies and anabasine, an additive effect was observed.
Subject(s)
Anabasine/pharmacology , Antibodies/pharmacology , Cytokines/blood , Inflammation Mediators/blood , Sepsis/mortality , Tumor Necrosis Factor-alpha/immunology , alpha7 Nicotinic Acetylcholine Receptor/agonists , Animals , Disease Progression , Female , Male , Mice , Sepsis/blood , Sepsis/pathology , Time Factors , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
The results of experiments on noninbred albino rats showed that the acute intoxication with carbon tetrachloride (CT) at a dose of 1 LD50 reduced the parameters of cellular immune response and function of Th1 cells more significantly than the levels of humoral immune response and Th2-lymphocyte function, decreases the blood content of immunoregulatory cytokines IFN-g, IL-2, IL-4 and anti-inflammatory cytokine IL-13, while not changing the concentration of anti-inflammatory cytokine IL-10 and increasing the concentration of pro-inflammatory cytokine IL-6. The application of unithiol, tocopherol acetate, and combinations partially restores the parameters examined. The combined effects of drugs during intoxication with CT does not exceed their separate action.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Carbon Tetrachloride Poisoning/drug therapy , Immunity, Innate/drug effects , Unithiol/pharmacology , alpha-Tocopherol/pharmacology , Animals , Animals, Outbred Strains , Carbon Tetrachloride Poisoning/blood , Carbon Tetrachloride Poisoning/immunology , Carbon Tetrachloride Poisoning/pathology , Drug Therapy, Combination , Female , Homeostasis/immunology , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-13/blood , Interleukin-2/blood , Interleukin-4/blood , Interleukin-6/blood , Male , Rats , Th1 Cells/immunology , Th1-Th2 Balance/drug effects , Th2 Cells/immunologyABSTRACT
Experiments on outbred albino rats showed that chronic nitrile acrylate intoxication (60 days, 0.05 LD50 per day subcutaneously) led to reduction of T-dependent humoral immune response (T-independent humoral immune response was less affected); parameters cell immunity were suppressed to a greater extent than parameters of humoral immune reactions. Equal attenuation of the functions of Th1 and Th2 lymphocytes, decrease of the blood levels of immunoregulatory, pro- and anti-inflammatory cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-13), and decrease of acetyl cholinesterase activity in thymic and splenic T lymphocytes were observed.
Subject(s)
Acrylates/toxicity , Cytokines/blood , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Nitriles/toxicity , Acetylcholinesterase/metabolism , Animals , Enzyme-Linked Immunosorbent Assay , Rats , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunologyABSTRACT
Experiments on noninbred albino rats showed that a chronic exposure to organophosphorus compounds (carbophos and metaphos, 30 days, total dose 0.3 LD50) is primarily followed by a decrease in the immune reactions and IFN-γ associated with Th1 lymphocyte function (in comparison with the immune response due to activation of Th2 cells by IL-4). The concentrations of IL-2, IL-6, and IL-10 in the blood decreased after 30-day intoxication. The immune reactions associated with functional activity of Th1 and Th2 lymphocytes were shown to decrease similarly after chronic treatment with organophosphorus compounds for 60 days (total dose 0.6 LD50). This exposure was accompanied by a decrease in the concentrations of IFN-γ, IL-4, IL-2, and IL-6, but had no effect on the level of IL-10 in the blood.
Subject(s)
Cytokines/blood , Organophosphorus Compounds/toxicity , Th1 Cells/drug effects , Th2 Cells/drug effects , Animals , Interferon-gamma/blood , Lethal Dose 50 , Malathion , Methyl Parathion , Organophosphorus Compounds/immunology , Rats , Th1 Cells/pathology , Th2 Cells/pathology , Time FactorsABSTRACT
It was established in experiments on noninbred mice that activation of α-7n acetylcholine receptors (α-7n AChR) by anabasine in single doses of 1.0 and 5.0 mg/kg for 2 h before modeling sepsis (intraperitoneal injection of E. coli) cause a significant dose-dependent reduction of mortality of mice due to a decrease in the amount of proinflammatory cytokines TNF-α, IL-1ß, and IL-6 in the blood. Anabasine in single doses of 0.1 mg/kg had no significant impact on the studied parameters.
Subject(s)
Anabasine/pharmacology , Escherichia coli Infections/drug therapy , Nicotinic Agonists/pharmacology , Sepsis/drug therapy , alpha7 Nicotinic Acetylcholine Receptor/agonists , Animals , Animals, Outbred Strains , Dose-Response Relationship, Immunologic , Escherichia coli/growth & development , Escherichia coli/pathogenicity , Escherichia coli Infections/immunology , Escherichia coli Infections/microbiology , Escherichia coli Infections/mortality , Female , Interleukin-1beta/blood , Interleukin-6/blood , Male , Mice , Sepsis/immunology , Sepsis/microbiology , Sepsis/mortality , Survival Analysis , Tumor Necrosis Factor-alpha/blood , alpha7 Nicotinic Acetylcholine Receptor/metabolismABSTRACT
It has been established in experiments on noninbred rats that chronic intoxication with 1,2-dichloroethane (30 days; total dose 0.9LD50; daily dose 0.03 mg/kg body weight) causes a reduction of immune responses, decreases the activity of acetylcholinesterase (AChE) of T-lymphocytes, reduces the concentration of blood cytokines (IFN-gamma, IL-2, IL-4, IL-6, while not affecting the content of IL-10), and damages to a greater degree Th1 cells as compared to Th2 lymphocytes. The administration of polyoxidonium (daily dose, 150 mg/kg, for 7 days,) partially restored the immune status, the activity of AChE T cells, and the content of cytokines in the blood.
Subject(s)
Acetylcholinesterase/immunology , Cytokines/immunology , Ethylene Dichlorides/toxicity , Immunologic Factors/pharmacology , Piperazines/pharmacology , Polymers/pharmacology , Th1 Cells/immunology , Th2 Cells/immunology , Animals , Female , Male , RatsABSTRACT
Experiments on albino outbred rats showed that chronic poisoning with organophosphorus compounds (Russian VX, and sarin) for 30 days in a total dose of 0.3 DL50 (0.01 DL50 daily) is followed by a decrease in phagocytic and metabolic activity of neutrophils. The reduction of functional activity of monocyte phagocytic system was stipulated by the stimulation of N-cholinergic receptors of these cells. These changes were accompanied by a decrease in blood concentration of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6).
Subject(s)
Cholinesterase Inhibitors/toxicity , Cytokines/metabolism , Neutrophils/physiology , Organothiophosphorus Compounds/toxicity , Phagocytosis/drug effects , Sarin/toxicity , Animals , Animals, Outbred Strains , Female , Inflammation Mediators , Lethal Dose 50 , Male , Neutrophils/drug effects , Nicotine/toxicity , Nicotinic Agonists/toxicity , RatsABSTRACT
Stimulation of nicotinic and muscarinic cholinoreceptors (nAChR, mAChR) in outbred albino mice with nicotine and aceclidine, respectively, in single equilethal doses 0.5 DL(50)6 h before sepsis induction significantly reduced animal mortality due to a decrease in blood concentrations of proinflammatory cytokines IL-1ß, IL-6, and MIP-2. Stimulation of mAChR (injection of aceclidine) stimulated the neutrophilic phagocytic and metabolic activity. Realization of the cholinergic anti-inflammatory pathway (stimulation of the peripheral nicotinic cholinoreceptors (α7nAChR) and central muscarinic cholinoreceptors (mAChR) was modulated by stimulation of the muscarinic cholinoreceptors of the phagocytic monocytic system cells.
Subject(s)
Receptors, Muscarinic/metabolism , Receptors, Nicotinic/metabolism , Sepsis/physiopathology , Signal Transduction/drug effects , Animals , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Mice , Monocytes/drug effects , Nicotine/pharmacology , Phagocytosis/drug effects , Quinuclidines/pharmacology , Signal Transduction/physiologyABSTRACT
Experiments on outbred albino mice have shown that proserine (reversible cholinesterase inhibitor) and nicotine (nicotinic receptor agonist) in a equivalent dose of 0.2 DL(50)injected 2 h before sepsis induction significantly reduced animal mortality from experimental infection due to reduction of blood concentrations of proinflammatory cytokines TNF-α, IL-1ß, and IL-6.
Subject(s)
Cholinesterase Inhibitors/administration & dosage , Escherichia coli Infections/drug therapy , Neostigmine/administration & dosage , Nicotine/administration & dosage , Nicotinic Agonists/administration & dosage , Sepsis/drug therapy , Animals , Animals, Outbred Strains , Drug Therapy, Combination , Escherichia coli/drug effects , Escherichia coli/growth & development , Escherichia coli Infections/immunology , Escherichia coli Infections/microbiology , Escherichia coli Infections/mortality , Female , Interleukin-1beta/blood , Interleukin-1beta/immunology , Interleukin-6/blood , Interleukin-6/immunology , Male , Mice , Sepsis/immunology , Sepsis/microbiology , Sepsis/mortality , Survival Rate , Time Factors , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunologyABSTRACT
Experiments on noninbred rats showed that the chronic intoxication with organophosphorus compounds sarin and methylparathion (30 days; total dose, 0.9 LD50; single daily dose, 0.03 mg/kg,) significantly decreases the immune responses and reduces the concentrations of blood cytokines IFN-gamma, IL-2, IL-4, IL-6, and IL-10. The damage is more pronounced in Th1 cells than in Th2 lymphocytes. The administration of imunofan (single daily dose, 20 microg/kg) for 5 days partly recovers the immune status and the content of cytokines in the blood.
Subject(s)
Immunity, Innate/drug effects , Immunologic Factors/administration & dosage , Methyl Parathion/toxicity , Oligopeptides/administration & dosage , Sarin/toxicity , Th1 Cells/drug effects , Animals , Cholinesterase Inhibitors/toxicity , Female , Hypersensitivity, Delayed/immunology , Immunologic Factors/therapeutic use , Injections, Intramuscular , Injections, Subcutaneous , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-2/blood , Interleukin-4/blood , Interleukin-6/blood , Male , Oligopeptides/therapeutic use , Rats , Th1 Cells/cytology , Th1 Cells/immunology , Th2 Cells/cytology , Th2 Cells/drug effects , Th2 Cells/immunologyABSTRACT
It is established in experiments on noninbred rats that the use of imunofan (20 mg/kg daily) and polyoxidonium (150 mg/kg daily) for 7 days on the background of chronic intoxication with organophosphorus agent VX (0.01 LD50, single daily treatment for 30 days) resulted in almost complete recovery of phagocytic-metabolic activity of neutrophils, the content of lysozyme, cationic protein of platelet, and levels of proinflammatory cytokines TNFa, IL-1b and IL-6 in the blood. The administration of T-activin (20 mg/kg daily for 7 days) restores these parameters insignificantly. The maximum overall stimulatory effect was produced by polyoxidonium, while the minimum effect was observed for T-activin.
Subject(s)
Antidotes/pharmacology , Chemical Warfare Agents/toxicity , Immunologic Factors/pharmacology , Oligopeptides/pharmacology , Organothiophosphorus Compounds/toxicity , Piperazines/pharmacology , Polymers/pharmacology , Animals , Antidotes/therapeutic use , Female , Gas Poisoning/drug therapy , Gas Poisoning/immunology , Immunologic Factors/therapeutic use , Interleukin-1beta/blood , Interleukin-6/blood , Male , Muramidase/blood , Neutrophils/drug effects , Neutrophils/immunology , Oligopeptides/therapeutic use , Organothiophosphorus Compounds/antagonists & inhibitors , Peptides/pharmacology , Phagocytosis/drug effects , Piperazines/therapeutic use , Polymers/therapeutic use , Rats , Thymus Extracts/pharmacology , Tumor Necrosis Factor-alpha/bloodABSTRACT
Experiments on outbred mice showed that acetylcholine chloride in a dose of 20 mg/kg 6 h after subcutaneous injection significantly reduces mortality of mice from sepsis induced by intraperitoneal injection of 2×10(9) E. coli bacterial bodies and the blood levels of proinflammatory cytokines TNF-α, IL-1ß, and IL-6.
Subject(s)
Acetylcholine/therapeutic use , Cytokines/blood , Sepsis/drug therapy , Animals , Enzyme-Linked Immunosorbent Assay , Escherichia coli , Female , Interleukin-1beta , Interleukin-6 , Male , Mice , Sepsis/microbiology , Sepsis/mortality , Tumor Necrosis Factor-alphaABSTRACT
Experiments of outbred albino rats showed that chronic ethanol intoxication (20 days, summary dose 5 LD(50)) inhibited immune reactions mainly mediated by Th1-cells, increased blood corticosterone concentration, reduced T-lymphocyte acetylcholinesterase activity, blood concentrations of IFN-γ, IL-2, IL-4, IL-10, and increased IL-6 level.