ABSTRACT
NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome has recently become an intriguing target of several chronic and viral diseases. Here, we argue that targeting NLRP3 inflammasome could be a strategy to prevent cardiovascular outcomes [fulminant myocarditis, heart failure, venous thromboembolism (VTE)] and acute respiratory distress syndrome (ARDS) in patients with SARS-CoV-2 infection. We discuss the rationale for NLRP3 targeting in clinical trials as an effective therapeutic strategy aimed to improve prognosis of COVID-19, analyzing the potential of two therapeutic options (tranilast and OLT1177) currently available in clinical practice.
Subject(s)
Cardiovascular Diseases/prevention & control , Coronavirus Infections/diagnosis , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pneumonia, Viral/diagnosis , Betacoronavirus/isolation & purification , COVID-19 , Clinical Trials as Topic , Coronavirus Infections/virology , Cytokines/metabolism , Humans , Inflammasomes/metabolism , Myocarditis/prevention & control , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Nitriles/therapeutic use , Pandemics , Pneumonia, Viral/virology , Prognosis , SARS-CoV-2 , Venous Thromboembolism/prevention & control , ortho-Aminobenzoates/therapeutic useABSTRACT
A rapid and selective assay of morphine and its 3- and 6-glucuronides in serum, based on high-performance liquid chromatography-electrospray mass spectrometry has been developed. The analytes and the internal standard, codeine or naltrexone, were subjected to solid-phase extraction, using ethyl solid-phase extraction columns, prior to chromatography. A reversed-phase column and a gradient mobile phase consisting of water and methanol were used. The mass spectrometer was operated in the selected-ion monitoring mode. The following ions were used: m/z 286 for morphine, m/z 300 for codeine, m/z 342 for naltrexone, and m/z 462 for morphine 3- and 6-glucuronides. The limit of quantitation observed with this method was 10 ng/ml morphine, 50 ng/ml morphine-6-glucuronide and 100 ng/ml morphine-3-glucuronide. The present method proved useful for the determination of serum levels of the parent drug and its metabolites in pain patients, heroin addicts and in morphine-treated mice.
Subject(s)
Morphine Derivatives/analysis , Morphine Derivatives/pharmacokinetics , Morphine/analysis , Morphine/pharmacokinetics , Animals , Calibration , Chromatography, High Pressure Liquid , Heroin Dependence/blood , Humans , Male , Mass Spectrometry , Mice , Mice, Inbred C57BL , Neoplasms/blood , Reference StandardsABSTRACT
A rapid and selective assay of nicotine, cotinine and trans-3'-hydroxycotinine in human serum, based on high-performance liquid chromatography with UV detection has been developed. The compounds were subjected to solid-phase extraction, using Extrelut 1 cartridges. Recoveries were ca. 95% for nicotine, 90% for cotinine and 50-55% for trans-3'-hydroxycotinine. The limit of quantitation observed with this method was 10 ng/ml for nicotine and 5 ng/ml for each of the metabolites. The compounds were also identified using high-performance liquid chromatography with particle beam mass spectrometry, to confirm their presence in human serum.
Subject(s)
Nicotine/blood , Chromatography, High Pressure Liquid , Cotinine/analogs & derivatives , Cotinine/blood , Humans , Mass Spectrometry , Reference Standards , Smoking/blood , Spectrophotometry, UltravioletABSTRACT
The effects of acute and chronic zidovudine (AZT) administration on immunologic test responses of mice were studied. The effects of AZT administration combined with morphine or methadone treatment, were also studied separately comparing the effects of each drug. We noted that AZT-treatment did not modify the T-lymphocyte subsets (L3T4/LyT2 rate), whereas morphine-treatment and AZT plus morphine treatment decreased the percentage of T helper cells. Acute and chronic AZT-treatment increased Natural Killer cell (NK) activity and also recovered the decreased NK cell activity produced by morphine-treatment. AZT-treatment, morphine-treatment, AZT plus morphine treatment and AZT plus methadone treatment strongly depressed the phagocytic physiological activity of Polymorphonuclear leukocytes (PMNs). Another evidence of immunologic responsiveness against AZT was the reduction of the mitogenic and antigenic response of lymphocytes. These results suggest a negative role of AZT-treatment especially on phagocytic activity and confirms a depressive effect of morphine-treatment on several immune functions studied. Furthermore, there is no indication of additive or synergistic toxic effects of AZT, morphine and methadone on the immune functions above that seen with each of these drugs when tested alone.
