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Intravascular bubble formation and symptoms of decompression sickness have been reported during repetitive deep breath-hold diving. Therefore we examined the pattern of blood N2 kinetics during and after repetitive breath-hold diving. To study muscle N2 uptake and release, we measured brachial venous N2 partial pressure (PN2) in nine professional Korean breath-hold divers (ama) during a 3-h diving shift at approximately 4 m seawater depth and up to 4 h after diving. PN2 was determined with the manometric Van Slyke method. Diving time and depth were recorded using a backpack computer-assisted dive longer that allowed calculating the surface-to-depth time ratio to derive the effective depth. With the assumption that forearm muscle N2 kinetics follow the general Haldanian principles of compression and decompression, i.e., forearm muscle is a single compartment with a uniform tissue PN2 equal to venous PN2, PN2 data were fitted to monoexponential functions of time. In the early phase of the diving shift, PN2 rapidly increased to 640 Torr (half time = 6 min) and then slowly declined to baseline levels (half time = 36 min) after the work shift. Peak PN2 levels approximated the alveolar PN2 derived from the effective depth. We conclude that forearm muscle N2 kinetics are well described by a Haldanian single-compartment model. Decompression sickness is theoretically possible in the ama; it did not occur because the absolute PN2 remained low due to the shallow working depth of the ama we studied.

Background We previously found that GADD45b, which is associated with cellular stress response and apoptosis regulation, contributes to sorafenib resistance in HCC cells. The present study explored the role of GADD45γ, another GADD45 family protein, in HCC treatment. Methods HCC cell lines tested included Huh-7, HepG2, Hep3B, Huh-7R, HepG2R, the latter two sorafenib-resistant cell lines established by continuously exposure of Huh-7 and HepG2 cells to sorafenib. GADD45γ expression was examined by quantitative real-time PCR (qRT-PCR) and western blotting. Control of GADD45γ transcription was examined by luciferase reporter assay using a series of reporter plasmids with deletions or site-directed mutants of the 5′-flanking region of GADD45γ promoter. Apoptosis was analyzed by flow cytometry and western blotting. Expression of GADD45γ in human HCC tumor tissues was measured by qRT-PCR and immunohistochemistry. Results GADD45γ mRNA and protein levels were increased after sorafenib independent of cellular MEK/ERK activity. GADD45γ induction was more prominent in sorafenib-sensitive HCC cells (Huh-7 and HepG2, IC50 6-7 µM) than in sorafenib-resistant HCC cells (Hep3B, Huh-7R and HepG2R, IC50 12-15 µM). Knockdown of GADD45γ expression partially abrogated the pro-apoptotic effects of sorafenib in sorafenib-sensitive cells but not sorafenib-resistant cells. The region -449/ - 82 in the 5′-flanking region of GADD45γ promoter was found crucial for GADD45 gamma induction by sorafenib. Decreased GADD45γ expression in HCC tumor tissue was associated with worse overall survival in patients who underwent surgery for HCC. Conclusions Induction of GADD45γ expression contributes to sorafenib-induced apoptosis in HCC cells. The role of GADD45γ as a predictive biomarker for sorafenib sensitivity in HCC warrants further exploration. (Supported by grants NSC-100-2325-B-002 -042, NSC 100-2314-B-002 -058-MY3, DOH100-TD-B-111-001, and NHRI-EX101-9911BC.)

Arterial oxygen saturation during breath-hold diving has not previously been measured continuously. We devised a submersible, waterproof, backpack computer to continuously record heart rate, depth, and arterial oxygen saturation (SPO2) as determined by earlobe pulse oximetry. Our measurements showed that one assisted (Funado) diver had reduced SPO2 values immediately after surfacing from 22 dives which lasted 23-76 s, from a mean of 99 +/- 1% SPO2 to 96 +/- 3% SPO2. SPO2 returned to 97 +/- 2% within 15 s after surfacing (P0.05 surface value differs from predive base line). Four unassisted (Cachido) divers showed no significant reduction of mean predive SPO2 below 98 +/- 2% at any time during the dive or recovery period in 92 routine dives lasting from 15 to 44 s. Upon surfacing from diving, mean SPO2 was 98 +/- 2% and the mean SPO2 15 s after surfacing was 97 +/- 3% for the unassisted divers. Three Cachido divers were asked to dive and breath hold for as long as possible. Mean SPO2 at the conclusion of breath holding was 73% after an average dive and breath hold lasting 69 s.

Korean female unassisted divers (cachido ama) breath-hold dive > 100 times to depths of 3–7 m during a work day. We sought to determine the extent of arterial hypoxemia during normal working dives and reasonable time limits for breath-hold diving by measuring radial artery blood gas tensions and pH in five cachido ama who dove to a fixed depth of 4–5 m and then continued to breath hold for various times after their return to the surface. Eighty-two blood samples were withdrawn from indwelling radial artery catheters during 37 ocean dives. We measured compression hyperoxia [arterial PO2 = 141 +/- 24 (SD) Torr] and hypercapnia (arterial PCO2 = 46.6 +/- 2.4 Torr) at depth. Mean arterial PO2 near the end of breath-hold dives lasting 32–95 s (62 +/- 14 s) was decreased (62.6 +/- 13.5 Torr). Mean arterial PCO2 reached 49.9 +/- 5.4 Torr. Complete return of these values to their baseline did not occur until 15–20 s after breathing was resumed. In dives of usual working duration (< 30 s), blood gas tensions remained within normal ranges. Detailed analysis of hemoglobin components and intrinsic oxygenation properties revealed no evidence for adaptive changes that could increase the tolerance of the ama to hypoxic or hypothermic conditions associated with repetitive diving.

Major increases of hemoglobin concentration and hematocrit, possibly secondary to splenic contraction, have been noted during diving in the Weddell seal. We sought to learn whether this component of the diving response could be present in professional human breath-hold divers. Splenic size was measured ultrasonically before and after repetitive breath-hold dives to approximately 6-m depth in ten Korean ama (diving women) and in three Japanese male divers who did not routinely practice breath-hold diving. Venous hemoglobin concentration and hematocrit were measured in nine of the ama and all Japanese divers. In the ama, splenic length and width were reduced after diving (P = 0.0007 and 0.0005, respectively) and calculated splenic volume decreased 19.5 +/- 8.7% (mean +/- SD, P = 0.0002). Hemoglobin concentration and hematocrit increased 9.5 +/- 5.9% (P = 0.0009) and 10.5 +/- 4% (P = 0.0001), respectively. In Japanese male divers, splenic size and hematocrit were unaffected by repetitive breath-hold diving and hemoglobin concentration increased only slightly over baseline (3.0 +/- 0.6%, P = 0.0198). Splenic contraction and increased hematocrit occur during breath-hold diving in the Korean ama.