CK2 (official acronym for casein kinase 2 or II) is a potent suppressor of apoptosis in response to diverse apoptotic stimuli —thus its molecular downregulation or activity inhibition results in potent induction of cell death. CK2 downregulation is known to impact mitochondrial apoptotic circuitry but the underlying mechanism(s) remain unclear. Utilizing prostate cancer cell lines subjected to CK2-specific inhibitors which cause loss of cell viability, we have found that CK2 inhibition in cells causes rapid early decrease in mitochondrial membrane potential (Δψm). Cells treated with the CK2 inhibitors TBB (4,5,6,7-tetrabromobenzotriazole) or TBCA (tetrabromocinnamic acid) demonstrate changes in Δψm which become apparent within 2 h, i.e., significantly prior to evidence of activation of other mitochondrial apoptotic signals whose temporal expression ensues subsequent to loss of Δψm. Further, we have demonstrated the presence of CK2 in purified mitochondria and it appears that the effect on Δψm evoked by inhibition of CK2 may involve mitochondrial localized CK2. Results also suggest that alterations in Ca2+ signaling may be involved in the CK2 mediated regulation of Δψm and mitochondrial permeability. Thus, we propose that a key mechanism of CK2 impact on mitochondrial apoptotic circuitry and cell death involves early loss of Δψm which may be a primary trigger for apoptotic signaling and cell death resulting from CK2 inhibition.

BackgroundScreening for neonatal hyperbilirubinaemia in the postnatal ward has traditionally been performed using serum bilirubin sampling, but this has significant drawbacks such as risk of infection and slower reporting time.ObjectiveWe aimed to assess the impact of introducing transcutaneous bilirubin (TcBR) testing using TcBR nomogram on the number of serum bilirubin samples sent.MethodsA before-and-after study was performed following the introduction of a protocol integrating the use of the Dragger JM-105 transcutaneous bilirubinometer in the postnatal ward. Only babies born at ≥37 weeks of gestation, weighing ≥2500 g who presented with jaundice after the first 24 hours and within the first 7 days of life were included in the study. The number of total serum bilirubin samples (TSBRs) sent were compared for the 6-month periods before and after (a total of 12 months) implementation of the new protocol.ResultsIn the pre-implementation phase, a total of 882 (49%) out of 1815 babies had at least one serum bilirubin sample taken as opposed to a total of 236 (17%) out of 1394 babies in the post-implementation phase. The odds of performing TSBRs at least one time among babies in post-implementation phase were 79% lower than in pre-implementation phase (OR 0.21, 95% CI 0.18 to 0.25). We also estimated a significant cost saving of approximately US$1800 over a period of 6 monthsConclusionTcBR testing used in conjunction with our proposed nomogram significantly reduces the need for serum bilirubin sampling.