[With the Characteristics of Chronic Pain Patients, Can the Therapeutic Effect of Antidepressant Duloxetine be Predicted?].

BACKGROUND: Duloxetine, an antidepressant, is used for treatment of pain, but the factors related to its effectiveness are not well known, and therefore we have performed a retrospective study. METHODS: Over a 22-month period from June 2012 patients with pain lasting for 3 months or more, with an NRS of 4 or higher, and given duloxetine within 3 months from their first diagnosis, were extracted from the medical records. These patients were compared and studied regarding their scores of the HADS (hos- pital anxiety and depression scale) at the time of first visit, duration of the disease, type of patient, and treat- ment effect after 1 month. RESULTS: The subjects were 61 patients, and they were categorized based on the presence of anxiety, the presence of dysphoria whether from organic or inor- ganic condition, and the duration of the disease, and no significant difference in the effectiveness of duloxetine was found. CONCLUSIONS: Duloxetine had an overall effectiveness of 50.8%, regardless of the presence of anxiety or depression, the duration of the disease and the type of diseases.

Anti-inflammatory effects of perioperative intensive insulin therapy during cardiac surgery with cardiopulmonary bypass.

PURPOSE: Recent studies have reported that controlling blood glucose with insulin can suppress systemic inflammation. In the present study, we evaluated how perioperative intensive insulin therapy (IIT) influences the inflammatory response in an artificial pancreas during cardiac surgery with cardiopulmonary bypass. METHODS: We randomly divided the patients undergoing cardiac surgery with cardiopulmonary bypass into two groups: an IIT group (n = 13) and a conventional treatment (CT) group (n = 12). For the IIT group, blood glucose control was initiated with an artificial pancreas at initiation of surgery. Blood glucose was maintained at 100 mg/dl until 24 h postoperatively. Blood samples were collected to determine changes in serum cytokine levels over time. RESULTS: Patients' characteristics did not differ significantly between groups. Blood glucose levels were significantly higher in the CT group after surgery. Serum levels of tumor necrosis factor-α, interleukin-6, and high-mobility group box 1 were higher in the CT group than in the IIT group. CONCLUSIONS: Use of IIT in the artificial pancreas during the perioperative period significantly decreased the inflammatory response. Moreover, we did not find evidence of hypoglycemia in those treated with IIT. This suggests that use of IIT in an artificial pancreas can be safe and effective for critically ill patients.

Remifentanil and glucose suppress inflammation in a rat model of surgical stress.

PURPOSE: Postoperative stress produces an inflammatory response. Recent studies have shown that narcotic analgesics suppress the immune system. Nutritional management during perioperative care has also been reported to affect inflammation. We therefore examined whether remifentanil or glucose administration could ameliorate postsurgical inflammatory responses using a rat model of surgical stress. METHODS: We divided male Wistar rats randomly into five groups: (1) control, (2) sevoflurane+lactated Ringer's solution, (3) sevoflurane+lactated Ringer's solution with 1% glucose, (4) sevoflurane+remifentanil+lactated Ringer's solution, and (5) sevoflurane+remifentanil+ lactated Ringer's solution with 1% glucose. In all groups, serum samples were obtained at various time points after surgery, and secreted cytokine concentrations were determined. In addition, we assessed the activation of protein kinase B (Akt) and forkhead/winged helix box class O (FOXO3), which play a role in gluconeogenesis/stress responses. RESULTS: Surgical stress increased the serum concentrations of tumor necrosis factor-α and interleukin-6. Groups receiving remifentanil with anesthesia showed an attenuated inflammatory response. The inflammatory response was also reduced by administering 1% glucose. Furthermore, 1% glucose induced Akt and FOXO3 phosphorylation in the quadriceps femoris muscle 12 h after surgery. CONCLUSIONS: Anesthesia based on remifentanil and perioperative administration of lactated Ringer's solution containing 1% glucose may be able to control inflammatory responses caused by surgical stress.

Catecholamine-resistant shock and hypoglycemic coma after cardiotomy in a patient with unexpected isolated ACTH deficiency.

Isolated adrenocorticotropic hormone (ACTH) deficiency is an extremely rare disease in which ACTH-producing cells of the pituitary gland are selectively damaged. The resulting decline in ACTH production and secretion results in chronic secondary adrenocortical insufficiency. The patient in this case did not present with adrenal insufficiency symptoms prior to surgery. However, after cardiotomy under extracorporeal circulation, the patient lapsed into a catecholamine-resistant shock and hypoglycemic coma. Acute adrenal insufficiency was strongly suspected, and the patient was diagnosed with isolated ACTH deficiency after careful examination. Because the demand for cortisol increases after highly invasive surgeries, cortisol supplementation therapy is essential for patients with complications from isolated ACTH deficiency. There is a high risk of a lethal outcome when surgery is carried out without a diagnosis, as in this case. Therefore, cortisol must be supplemented without delay when acute adrenal insufficiency is suspected during the perioperative period.

Mechanism of inhibition by C-terminal alpha-helices of the epsilon subunit of Escherichia coli FoF1-ATP synthase.

The epsilon subunit of bacterial FoF1-ATP synthase (FoF1), a rotary motor protein, is known to inhibit the ATP hydrolysis reaction of this enzyme. The inhibitory effect is modulated by the conformation of the C-terminal alpha-helices of epsilon, and the "extended" but not "hairpin-folded" state is responsible for inhibition. Although the inhibition of ATP hydrolysis by the C-terminal domain of epsilon has been extensively studied, the effect on ATP synthesis is not fully understood. In this study, we generated an Escherichia coli FoF1 (EFoF1) mutant in which the epsilon subunit lacked the C-terminal domain (FoF1epsilonDeltaC), and ATP synthesis driven by acid-base transition (DeltapH) and the K+-valinomycin diffusion potential (DeltaPsi) was compared in detail with that of the wild-type enzyme (FoF1epsilonWT). The turnover numbers (kcat) of FoF1epsilonWT were severalfold lower than those of FoF1epsilonDeltaC. FoF1epsilonWT showed higher Michaelis constants (Km). The dependence of the activities of FoF1epsilonWT and FoF1epsilonDeltaC on various combinations of DeltapH and DeltaPsi was similar, suggesting that the rate-limiting step in ATP synthesis was unaltered by the C-terminal domain of epsilon. Solubilized FoF1epsilonWT also showed lower kcat and higher Km values for ATP hydrolysis than the corresponding values of FoF1epsilonDeltaC. These results suggest that the C-terminal domain of the epsilon subunit of EFoF1 slows multiple elementary steps in both the ATP synthesis/hydrolysis reactions by restricting the rotation of the gamma subunit.

Production of cloned pigs from adult somatic cells by chemically assisted removal of maternal chromosomes.

The present study demonstrated that brief treatment of in vitro-matured porcine oocytes with demecolcine results in a membrane protrusion that contains a condensed chromosome mass, which can be easily removed by aspiration. This simple, chemically assisted method for removing maternal chromosomes enabled the production of a large number of nuclear-transferred porcine eggs. The development of eggs whose chromosomes were removed by this procedure following transfer of somatic cell nuclei to the blastocyst stage was not significantly different among groups activated using different procedures (6% to 11%) and was also not different among donor cells of different origins (3% to 9%), except for cumulus cells (0.4%). After transfer of 180 to 341 nuclear-transferred eggs that received somatic cells to 6 recipients, 2 of the recipients produced 8 healthy cloned piglets from the heart cells of a female pig. The chemically assisted method for removing maternal chromosomes was also effective for bovine and rabbit eggs.