Nocturnal hypoxaemia is common in adults with sickle cell anaemia.

The symptoms and sequelae of sickle cell anaemia (SCA) are caused by the polymerization of deoxygenated sickle haemoglobin, and people with SCA may be uniquely susceptible to adverse outcomes from hypoxia and haemoglobin desaturation. We examined by oximetry adults (aged 18-45 years) with SCA presenting symptoms indicative of polysomnography, at a single institution, irrespective of treatment, for nocturnal hypoxaemia. Clinical labs and blood for in vitro assessments were taken upon enrolment and after 8-12 weeks of oxygen therapy or observation. Of 21 screened participants, nine (43%) had sufficient nocturnal hypoxaemia to warrant oxygen therapy (≥5 min at SpO2 ≤ 88%). Time spent at SpO2 ≤ 88% associated with age (p = 0.0092), annual hospitalizations (p = 0.0018) and anaemia (p = 0.0139), as well as plasma levels of TNFα (p = 0.0019) and IL-4 (p = 0.0147). Longitudinal analysis showed that WBC significantly decreased during the follow-up period in hypoxic individuals but not in non-hypoxic individuals (p = 0.0361 and p = 0.6969 respectively). Plasma levels of CCL2 and IL-1ra tended to increase, while levels of red blood cell reactive oxygen species tended to decrease with oxygen therapy. Overall, nocturnal hypoxaemia was common in this pilot study population and associated with plausible clinical comorbidities; oxygen therapy may decrease inflammation and oxidative damage in hypoxic individuals.

The α-ketoglutarate/Fe(II)-dependent dioxygenase VldW is responsible for the formation of validamycin B.

From A to B: Through detailed biochemical investigations, we discovered that VldW, an α-ketoglutarate/Fe(II)-dependent dioxygenase, regioselectively hydroxylates validamycin A to validamycin B. The results provide insights into the biosynthesis of hydroxylated validamycins and could be used to control the metabolic outcomes of the validamycin pathway.