Background and study aims It is important to examine the pharynx during
upper gastrointestinal endoscopy. Pharyngeal anesthesia using topical lidocaine
is generally used as pretreatment. In Japan, lidocaine viscous solution is the
anesthetic of choice, but lidocaine spray is applied when the former is
considered insufficient. However, the relationship between the extent of
pharyngeal anesthesia and accuracy of observation is unclear. We compared the
performance of lidocaine spray alone versus lidocaine spray combined with
lidocaine viscous solution for pharyngeal observation during transoral
endoscopy.
Patients and methods In this prospective, double-blinded, randomized
clinical trial conducted between January and March 2015, 327 patients were
randomly assigned to lidocaine spray alone (spray group, n = 157) or a
combination of spray and viscous solution (combination group, n = 170). We
compared the number of pharyngeal observable sites (non-inferiority test), pain
by visual analogue scale, observation time, and the number of gag reflexes
between the two groups.
Results The mean number of images of suitable quality taken at the
observable pharyngeal sites in the spray group was 8.33 (95 % confidence
interval [CI]: 7.94 – 8.72) per patient, and 8.77 (95 % CI: 8.49 – 9.05) per
patient in the combination group. The difference in the number of observable
pharyngeal sites was – 0.44 (95 % CI: – 0.84 to – 0.03, P = 0.01). There
were no differences in pain, observation time, or number of gag reflexes between
the 2 groups. Subgroup analysis of the presence of sedation revealed no
differences between the two groups for the number of pharyngeal observation
sites and the number of gag reflexes. However, the number of gag reflexes was
higher in the spray group compared to the combination group in a subgroup
analysis that looked at the absence of sedation.
Conclusions Lidocaine spray for pharyngeal anesthesia was not inferior to
lidocaine spray and viscous solution in terms of pharyngeal observation. It was
considered that lidocaine viscous solution was unnecessary for pharyngeal
observation. UMIN000016073
Notch1 is regulated by E3 ubiquitin ligases, with proteasomal degradation of the Notch intracellular domain affecting the transcription of target genes. cAMP response element-binding protein (CREB) mediates the transcription of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA). We assessed the relationship between HBV cccDNA and Notch signaling activities. HBV cccDNA levels and relative gene expression were evaluated in HBV-replicating cells treated with Jagged1 shRNA and a γ-secretase inhibitor. The effects of these factors in surgically resected clinical samples were also assessed. Notch inhibition suppressed HBV cccDNA and CREB-related expression but increased ITCH and NUMB levels. Proteasome inhibitor augmented HBV cccDNA, restored Notch and CREB expression, and inhibited ITCH and NUMB function. Increased HBV cccDNA was observed after ITCH and NUMB blockage, even after treatment with the adenylate cyclase activator forskolin; protein kinase A (PKA) inhibitor had the opposite effect. Notch activation and E3 ligase inactivation were observed in HBV-positive cells in clinical liver tissue. Collectively, these findings reveal that Notch signaling activity facilitates HBV cccDNA transcription via CREB to trigger the downstream PKA-phospho-CREB cascade and is regulated by E3 ubiquitin ligase-modulation of the Notch intracellular domain.
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