ABSTRACT
There are reports of children COVID-19 or COVID-19 like symptoms with hyperinflammatory multisystem syndrome, ARDS, gastrointestinal and atypical Kawasaki disease presenting to PICU worldwide temporally associated with COVID-19, for which there are important nutrition support considerations. As a result, the European Society of Pediatric and Neonatal Intensive Care - Metabolism, Endocrine and Nutrition group (ESPNIC-MEN) and paediatric nutritionists working in PICUs are being consulted regarding nutrition management of critically ill children with COVID-19 or COVID-19 like symptoms. Therefore, the aim of this short report is to provide a summary of nutrition support recommendations for critically ill children with COVID-19. They are based on the ESPNIC-MEN section recommendations published in January 2020 and surviving sepsis recommendations from February 2020.
Subject(s)
COVID-19/therapy , Nutritional Support/methods , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/therapy , Child , Critical Care/methods , Critical Illness , Enteral Nutrition/methods , Humans , Intensive Care Units, Pediatric , Nutritional StatusABSTRACT
New polyanionic compounds were obtained from radical addition of thiomalic acid and mercaptopropionic acid onto perallylated cyclodextrins (CDs) under UV irradiation with a catalytic amount of alpha,alpha'-azobis(isobutyronitrile). All these polyanions, bearing 18-48 carboxylate groups, inhibited human immunodeficiency virus type 1 (HIV-1) strain IIIB replication in MT-4 cells at a 50% inhibitory concentration (IC50) of 0.1-2.9 microM, while not being toxic to the host cells at concentrations up to 62 microM. These compounds were also active against a clinical HIV-1 isolate (HE) at >/=4-fold higher concentrations. Only some compounds showed activity against the two HIV-2 strains (ROD and EHO) but at higher concentrations than those required to inhibit HIV-1 (IIIB and HE) replication. In addition, these compounds were not active against the M-tropic HIV-1 strain BaL but were active against simian immunodeficiency virus [SIV (MAC251)]. These compounds were also inhibitory to the replication of human cytomegalovirus at an IC50 of 1-10 microM, but not herpes simplex virus (type 1 and type 2) or other (picorna-, toga-, reo-, orthomyxo-, paramyxo-, bunya-, rhabdo-, and poxvirus) viruses. Radical addition on perallylated CDs of a protected cysteine gave polyzwitterionic compounds. None of these last compounds proved inhibitory to the replication of HIV-1, HIV-2, or any of the other viruses tested.
Subject(s)
Anti-HIV Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Carboxylic Acids/chemical synthesis , Cyclodextrins/chemical synthesis , Animals , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Anti-HIV Agents/toxicity , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/toxicity , Carbohydrate Sequence , Carboxylic Acids/chemistry , Carboxylic Acids/pharmacology , Carboxylic Acids/toxicity , Cell Line , Chlorocebus aethiops , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Cyclodextrins/toxicity , DNA Viruses/drug effects , Dogs , HIV-1/drug effects , HIV-1/isolation & purification , HIV-2/drug effects , HeLa Cells , Humans , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Molecular Sequence Data , RNA Viruses/drug effects , Structure-Activity Relationship , Ultraviolet Rays , Vero Cells , Virus Replication/drug effectsABSTRACT
A new class of polyanionic compounds, inhibitors of human immunodeficiency virus, was obtained from radical addition of mercapto acid or mercapto ester on a perallylated carbohydrate under UV irradiation with a catalytic amount of AIBN. Unlike the polyanions that we have previously prepared by polymerization reactions, the compounds are structurally well defined. Polyanions bearing 16 carboxylate groups showed a 50% inhibitory concentration (IC50) of 0.1-4.1 micrograms/mL against HIV-1 in MT-4 cells while not being toxic to the host cells at concentrations up to 125 micrograms/mL. The most potent polyanions also proved active against human cytomegalovirus at concentrations of 1-14 micrograms/mL. No activity was observed against any of the other viruses tested (i.e., herpes simplex virus, vesicular stomatitis virus, Sindbis, Semliki forest, parainfluenza-3, Junin, Tacaribe, Coxsackie B4, polio-1, reo-1, or vaccinia virus).
Subject(s)
Anti-HIV Agents/pharmacology , Antiviral Agents/pharmacology , Carbohydrates/pharmacology , Micelles , Polymers/pharmacology , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/chemistry , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Carbohydrates/chemical synthesis , Carbohydrates/chemistry , Cell Line , Cytomegalovirus/drug effects , HIV-1/drug effects , HIV-2/drug effects , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Molecular Structure , Nitriles/pharmacology , Polyelectrolytes , Polymers/chemical synthesis , Polymers/chemistry , Ultraviolet RaysABSTRACT
In a double-blind, parallel-group comparative study, once-daily administration of a modified-release formulation of isradipine (Im, n = 189) was compared with twice-daily administration of the standard formulation (Is, n = 191). Following a 3- to 5-week placebo period, patients with a sitting diastolic blood pressure (sDBP) of greater than or equal to 100 mm Hg but less than or equal to 120 mm Hg were randomized to receive either Im at 5 mg once daily or Is at 2.5 mg twice daily for 6 weeks. A double-dummy technique was used to maintain blindness and no dosage titration was made. Blood pressure was always recorded in the morning before drug administration (12 h after the previous administration of Is or 24 h after the previous administration of Im). The mean sDBP was reduced significantly (p less than 0.001) and equally in both groups, and the normalization rate (sDBP less than or equal to 90 mm Hg) was 54% with Im and 55% with Is. Adverse events were slightly less frequent overall in the patients receiving Im than Is (23 vs. 28%, respectively) as was the incidence of typical dihydropyridine side effects such as flushing and headache. The results show that once-daily administration of 5 mg of Im is as effective and better tolerated than 2.5 mg twice daily of Is while providing adequate blood pressure control at the end of the 24-h dosing interval.