D-lactate is normally present in the blood of mammals at nanomolar concentrations due to methylglyoxal metabolism; millimolar d-lactate concentrations can arise due to excess gastrointestinal microbial production. Grain overload in ruminants, short-bowel syndrome in humans, and diarrhea in calves can all result in profound D-lactic acidemia, with remarkably similar neurological manifestations. In the past, D-lactate was thought to be excreted mainly in the urine, and metabolized slowly by the enzyme d-alpha-hydroxy acid dehydrogenase. More recent studies reported that mammals have a relatively high capacity for D-lactate metabolism and identified a putative mammalian D-lactate dehydrogenase. A growing body of literature is also emerging describing subclinical elevation of D-lactate as an indicator of sepsis and trauma. This article describes advances in the understanding of D-lactate metabolism, D-lactic acidosis in ruminants and humans, and subclinical elevation of d-lactate.

Wearing face masks is recommended for the prevention of contracting or exposing others to cardiorespiratory infections, such as COVID-19. Controversy exists on whether wearing face masks during vigorous exercise affects performance. We used a randomized, counterbalanced cross-over design to evaluate the effects of wearing a surgical mask, a cloth mask, or no mask in 14 participants (7 men and 7 women; 28.2 ± 8.7 y) during a cycle ergometry test to exhaustion. Arterial oxygen saturation (pulse oximetry) and tissue oxygenation index (indicator of hemoglobin saturation/desaturation) at vastus lateralis (near-infrared spectroscopy) were assessed throughout the exercise tests. Wearing face masks had no effect on performance (time to exhaustion (mean ± SD): no mask 622 ± 141 s, surgical mask 657 ± 158 s, cloth mask 637 ± 153 s (p = 0.20); peak power: no mask 234 ± 56 W, surgical mask 241 ± 57 W, cloth mask 241 ± 51 W (p = 0.49)). When expressed relative to peak exercise performance, no differences were evident between wearing or not wearing a mask for arterial oxygen saturation, tissue oxygenation index, rating of perceived exertion, or heart rate at any time during the exercise tests. Wearing a face mask during vigorous exercise had no discernable detrimental effect on blood or muscle oxygenation, and exercise performance in young, healthy participants (ClinicalTrials.gov, NCT04557605).

A series of 3,5-bis(arylidene)-4-piperidones 1 and related N-acryloyl analogues 2 were prepared as candidate cytotoxic agents with a view to discerning those structural features which contributed to bioactivity. A number of the compounds were markedly cytotoxic toward murine P388 and L1210 leukemic cells and also to human Molt 4/C8 and CEM neoplasms. Approximately 40% of the IC50 values generated were lower than the figures obtained for melphalan. In virtually all cases, the N-acyl compounds were significantly more bioactive than the analogues 1. In general, structure-activity relationships revealed that the cytotoxicity of series 1 was correlated positively with the size of the aryl substituents, while in series 2, a -sigma relationship was established. In particular, various angles and interatomic distances were obtained by molecular modeling, and the presence of an acryloyl group on the piperidyl nitrogen atom in series 2 affected the relative locations of the two aryl rings. This observation, along with some differences in distances between various atoms in series 1 and 2, may have contributed to the disparity in cytotoxicity between 1 and 2. The results obtained by X-ray crystallography of representative compounds were mainly in accordance with the observations noted by molecular modeling. Selected compounds interfered with the biosynthesis of DNA, RNA, and protein in murine L1210 cells, while others were shown to cause apoptosis in the human Jurkat leukemic cell line. This study has revealed the potential of these molecules for development as cytotoxic and anticancer agents.