Circadian clock signals in the adrenal cortex

Circadian secretion of steroid hormones by the adrenal cortex is required to maintain whole body homeostasis and to adequately respond to or anticipate environmental changes. The richly vascularized zona glomerulosa (ZG) cells in the pericapsular region regulate osmotic balance of body fluid by secreting mineralocorticoids responding to circulating bioactive substances, and more medially located zona fasciculata (ZF) cells regulate energy supply and consumption by secreting glucocorticoids under neuronal and hormonal regulation. The circadian clock regulates both steroidogenic pathways: the clock within the ZG regulates mineralocorticoid production via controlling rate-limiting synthetic enzymes, and the ZF secretes glucocorticoid hormones into the systemic circulation under the control of central clock in the suprachiasmatic nucleus. A functional biological clock at the systemic and cellular levels is therefore necessary for steroid synthesis and secretion.     

The observational study of delayed wound healing after tooth extraction in patients receiving oral bisphosphonate therapy

IntroductionIn this study, we investigated whether such a discontinuation of oral bisphosphonate (BP) for 3 months might influence the incidence of BP-related osteonecrosis of the jaw (BRONJ) and wound healing after tooth extraction in patients receiving oral BP therapy.Material and methodsThere were a total of 434 teeth in 201 patients (18 males and 183 females). The patients were divided into two groups depending on whether or not they underwent a 3-month discontinuation of BP therapy (BP? and BP+) before tooth extraction. In this observational study investigated delayed wound healing after tooth extraction in patients receiving oral BP therapy.ResultsIn all cases of the BP? group, there were no BRONJ although there was delayed wound healing in two cases. However, in one case of the BP+ group, oral BP was continued because it was deemed high risk to discontinue treatment by the patient's physician. In this case, an intraoral fistula was still present with bone exposure at 120 weeks after extraction (BRONJ stage 1).ConclusionThis study supports the idea of a drug holiday and encourages further clinical research on this topic of tooth extraction in patients receiving oral BP therapy.     

Comparison of PPIs and H2-receptor antagonists plus prokinetics for dysmotility-like dyspepsia

AIM: To compare efficacy of proton pump inhibitors (PPIs) with H₂-receptor antagonists (H₂RAs) plus prokinetics (Proks) for dysmotility-like symptoms in functional dyspepsia (FD).METHODS: Subjects were randomized to receive open-label treatment with either rabeprazole 10 mg od (n = 57) or famotidine 10 mg bid plus mosapride 5 mg tid (n = 57) for 4 wk. The primary efficacy endpoint was change (%) from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment.RESULTS: The improvement in dysmotility-like dyspepsia symptom score on day 28 was significantly greater in the rabeprazole group (22.5% ± 29.2% of baseline) than the famotidine + mosapride group (53.2% ± 58.6% of baseline, P < 0.0001). The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine + mosapride group (87.7% vs 59.6%, P = 0.0012). Rabeprazole therapy was the only significant predictor of treatment response (P < 0.0001), defined as a total symptom score improvement ≥ 50%.CONCLUSION: PPI monotherapy improves dysmotility-like symptoms significantly better than H₂RAs plus Proks, and should be the treatment of first choice for Japanese FD.     

Motor vehicle accidents: How should cirrhotic patients be managed?

Motor vehicle accidents (MVAs) are serious social issues worldwide and driver illness is an important cause of MVAs. Minimal hepatic encephalopathy (MHE) is a complex cognitive dysfunction with attention deficit, which frequently occurs in cirrhotic patients independent of severity of liver disease. Although MHE is known as a risk factor for MVAs, the impact of diagnosis and treatment of MHE on MVA-related societal costs is largely unknown. Recently, Bajaj et al demonstrated valuable findings that the diagnosis of MHE by rapid screening using the inhibitory control test (ICT), and subsequent treatment with lactulose could substantially reduce the societal costs by preventing MVAs. Besides the ICT and lactulose, there are various diagnostic tools and therapeutic strategies for MHE. In this commentary, we discussed a current issue of diagnostic tools for MHE, including neuropsychological tests. We also discussed the advantages of the other therapeutic strategies for MHE, such as intake of a regular breakfast and coffee, and supplementation with zinc and branched chain amino acids, on the MVA-related societal costs.     

Fish to meat intake ratio and cooking oils are associated with hepatitis C virus carriers with persistently normal alanine aminotransferase levels

Aim: Dietary habits are involved in the development of chronic inflammation; however, the impact of dietary profiles of hepatitis C virus carriers with persistently normal alanine transaminase levels (HCV‐PNALT) remains unclear. The decision‐tree algorithm is a data‐mining statistical technique, which uncovers meaningful profiles of factors from a data collection. We aimed to investigate dietary profiles associated with HCV‐PNALT using a decision‐tree algorithm. Methods: Twenty‐seven HCV‐PNALT and 41 patients with chronic hepatitis C were enrolled in this study. Dietary habit was assessed using a validated semiquantitative food frequency questionnaire. A decision‐tree algorithm was created by dietary variables, and was evaluated by area under the receiver operating characteristic curve analysis (AUROC). Results: In multivariate analysis, fish to meat ratio, dairy product and cooking oils were identified as independent variables associated with HCV‐PNALT. The decision‐tree algorithm was created with two variables: a fish to meat ratio and cooking oils/ideal bodyweight. When subjects showed a fish to meat ratio of 1.24 or more, 68.8% of the subjects were HCV‐PNALT. On the other hand, 11.5% of the subjects were HCV‐PNALT when subjects showed a fish to meat ratio of less than 1.24 and cooking oil/ideal bodyweight of less than 0.23 g/kg. The difference in the proportion of HCV‐PNALT between these groups are significant (odds ratio 16.87, 95% CI 3.40–83.67, P = 0.0005). Fivefold cross‐validation of the decision‐tree algorithm showed an AUROC of 0.6947 (95% CI 0.5656–0.8238, P = 0.0067). Conclusion: The decision‐tree algorithm disclosed that fish to meat ratio and cooking oil/ideal bodyweight were associated with HCV‐PNALT.     

Splenic artery ligation: A protection against hepatic ischemia/reperfusion injury in partially hepatectomized rats

Aim: In liver resection, the temporary occlusion of the hepatoduodenal ligament (Pringle maneuver) is often used. However, the maneuver causes ischemia/reperfusion (I/R) injury in the remnant liver. Heme oxygenase (HO)‐1 has a cytoprotective role against this injury. Our aim is to investigate whether splenic artery ligation induces HO‐1 expression in the liver and ameliorates the hepatic I/R injury in partially hepatectomized rats. Methods: Rats underwent splenic artery ligation by occluding the main splenic artery. Two days later, the total hepatic ischemia (Pringle maneuver) was conducted, and then a two‐thirds partial hepatectomy (PH) was performed just before the start of reperfusion. HO inhibitor was twice injected s.c. at 3 and 16 h before the Pringle maneuver. HO‐1 levels were determined by western blotting. Liver injury was biochemically assessed. Results: In normal rats, HO‐1 was highly expressed in the spleen, but not in the liver. Splenic artery ligation induced HO‐1 in the livers. When rats underwent 20 and 30 min of Pringle maneuver/PH, survival rates were 28% and 8%, respectively. Splenic artery ligation significantly improved both the survival rates: 73% and 56%, respectively. Under these conditions, administration of HO‐1 inhibitor at least partly negated the efficacy of splenic artery ligation. Splenic artery ligation also increased the recovery rate of the remnant liver mass and platelet counts in Pringle maneuver/PH‐treated rats. Conclusion: Splenic artery ligation was significantly effective on the hepatic I/R injury in partially hepatectomized rats. Induction of HO‐1 may be at least partly involved in the improvement of this injury.