Diagnostic and Pharmacological Potency of Creatine in Post-Viral Fatigue Syndrome

Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure. Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue levels of creatine in the brain, the rates of phosphocreatine resynthesis in the skeletal muscle, or the concentrations of the enzyme creatine kinase in the blood. Furthermore, supplemental creatine and related guanidino compounds appear to impact both patient- and clinician-reported outcomes in syndromes and maladies with chronic fatigue. This paper critically overviews the most common disturbances in creatine metabolism in various PVFS populations, summarizes human trials on dietary creatine and creatine analogs in the syndrome, and discusses new frontiers and open questions for using creatine in a post-COVID-19 world.

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Small metabolites and peptides in 17 snake venoms (Elapidae, Viperinae, and Crotalinae), were quantified using liquid chromatography-mass spectrometry. Each venom contains >900 metabolites and peptides. Many small organic compounds are present at levels that are probably significant in prey envenomation, given that their known pharmacologies are consistent with snake envenomation strategies. Metabolites included purine nucleosides and their bases, neurotransmitters, neuromodulators, guanidino compounds, carboxylic acids, amines, mono- and disaccharides, and amino acids. Peptides of 2–15 amino acids are also present in significant quantities, particularly in crotaline and viperine venoms. Some constituents are specific to individual taxa, while others are broadly distributed. Some of the latter appear to support high anabolic activity in the gland, rather than having toxic functions. Overall, the most abundant organic metabolite was citric acid, owing to its predominance in viperine and crotaline venoms, where it chelates divalent cations to prevent venom degradation by venom metalloproteases and damage to glandular tissue by phospholipases. However, in terms of their concentrations in individual venoms, adenosine, adenine, were most abundant, owing to their high titers in Dendroaspis polylepis venom, although hypoxanthine, guanosine, inosine, and guanine all numbered among the 50 most abundant organic constituents. A purine not previously reported in venoms, ethyl adenosine carboxylate, was discovered in D. polylepis venom, where it probably contributes to the profound hypotension caused by this venom. Acetylcholine was present in significant quantities only in this highly excitotoxic venom, while 4-guanidinobutyric acid and 5-guanidino-2-oxopentanoic acid were present in all venoms.

GC analysis of guanidino compounds in serum and urine of healthy volunteers and uremic patients using methylglyoxal and ethyl chloroformate as derivatizing reagent

Gas chromatographic determination of 9 guanidino compounds from the serum and urine of healthy volunteers and uremic patients.