Effects of interleukin-18 on diaphragm muscle contraction on rats

To evaluate the role of interleukin (IL)-18 in endotoxin-induced diaphragm muscle deterioration, we studied three treatment groups, namely, a saline+endotoxin group, an IL-18+endotoxin group and an IL-18 only group using Wistar rats. Five minutes after saline or IL-18 (0.25 microg) injection, E. coli endotoxin (30 mg/kg) was injected intraperitoneally. In the saline+endotoxin group, the force-frequency curves by ANOVA (p < 0.01), twitch tension (TT) and slope during contraction time (TT/CT) were significantly lower at 4 hours than those at 0 hours due to endotoxin (p < 0.01 and p < 0.05, respectively) and nitric oxide (NO) production had increased at 4 hours as shown by NADPH diaphorase staining. In the IL-18+endotoxin group, the decrement of the force-frequency curves in a higher frequency range (50-120 Hz), and the decrements of TT and TT/CT observed at 4 hours in the saline+endotoxin group were significantly prevented, and NO production was blocked at 4 hours. In the IL-18 only group, the force-frequency curves did not change except for fatigability, and NO production did not occur. It is suggested that IL-18 itself naturally blocks NO production, even when endotoxin coexists, resulting in the prevention of deterioration of diaphragm muscle contraction by endotoxin.     

Cancer-related intrusive thoughts as an indicator of poor psychological adjustment at 3 or more years after breast surgery: a preliminary study

Intrusive thoughts are one of the re-experiencing symptoms in posttraumatic stress disorder, and have been suggested as a predictor for the continuous presence of psychological distress in cancer survivors. The aim of this preliminary study was to examine the possibility of using cancer-related intrusive thoughts (CITs) as an indicator of psychological distress and adjustment after breast surgery. A consecutive series of ambulatory breast cancer survivors at 3 or more years after surgery were given the Structured Clinical Interview for DSM-IV (SCID) and self-report questionnaires, including Profile Of Mood States (POMS), Impact of Event Scale (IES) and Mental Adjustment to Cancer (MAC) scale, to measure psychological distress and/or adjustment. The SCID identified a history of CITs in 34 (46%) of the 74 participants. No significant differences were found in the POMS and IES psychological distress scores between subjects with and without a history of CITs. Subjects with a history of CITs showed significantly higher levels of anxious preoccupation, one of the MAC subscale scores. The association continued to be significant after controlling for potential confounders such as social support, depression, avoidance, arousal, and neuroticism. The results indicated that CITs might be useful for indicating poor psychological adjustment, but not distress, in patients at 3 or more years after breast surgery.     

Desensitization of the inhibitory effect of norepinephrine on insulin secretion from pancreatic islets of exercise-trained rats

The effect of exercise training (9 weeks of running) on norepinephrine-induced inhibition of insulin secretion was examined in rat islets. Insulin secretions from islets in the presence of glucose (> or =5.5 mmol/L) were significantly lower in trained (TR) than in control rats (CR). Norepinephrine inhibited 5.5 mmol/L glucose-stimulated insulin secretions and cyclic adenosine monophosphate (cAMP) contents in a dose-dependent manner in CR. Norepinephrine (10 micromol/L)-induced inhibition of insulin secretion was reversed by the blockade of the alpha(2)-adrenergic receptor in CR, but not in TR. Exercise training substantially shifted the dose-dependent curve for clonidine-induced inhibition of insulin secretions and that of cAMP contents to the right. Exercise training did not alter the density of the alpha(2)-adrenergic receptor either per islet or per protein of islet crude membrane. However, exercise training significantly reduced the protein expression of G alpha i-2 without change in G alpha i-2 mRNA. In CR but not in TR, norepinephrine significantly inhibited insulin secretions elicited by a combination of high glucose, a protein kinase C activator, and an adenylate cyclase activator under Ca(2+)-free conditions. Thus, exercise training appears to provoke a decreased expression of G alpha i-2 protein. This, at least in part, results in loss of the inhibitory effect of norepinephrine either on cAMP content or on insulin secretion at the post-calcium events in stimulus-secretion coupling, which, in turn, leads to the blunted inhibitory effects of norepinephrine on insulin secretion.     

Augmentation effects of lymphocyte activation by antigen-presenting macrophages on FDG uptake

OBJECTIVE: Research on FDG-uptake by blood cells has revealed that FDG is incorporated by macrophages and granulocytes, as well as activated lymphocytes. These characteristics of FDG suggest the possibility of visualizing the distribution of immunocytes in target organs. The aim of this study was to investigate if mouse spleen-derived lymphocytes, activated by macrophages presenting sheep red blood cell (sRBC) antigens, could be traced by FDG. METHODS: One percent of a sRBC suspension was injected into the peritoneal cavity of mice thereby creating immunity to the sRBC antigen. The splenocytes, consisting mostly of lymphocytes, were isolated, and serum containing the anti-sRBC antibody was mixed with sRBC to prepare sRBC-antibody complexes (sRBC-AbCs). Then five percent of a thioglycolate medium was injected into the peritoneal cavity of the same mice, and macrophages of ascitic cell origin were obtained. These macrophages were added to the sRBC-AbCs to induce sRBC antigen presenting macrophages. These were incubated with splenocytes obtained from sRBC immunized mouse (sRBC immunized splenocytes) or non-immunized splenocytes to induce a T cell immune response. [3H]deoxyglucose ([3H]DG) and FDG were incorporated in splenocytes, and the quantity of their uptake was measured. RESULTS: [3H]DG uptake by sRBC-immunized splenocytes was about eleven times as high as that of non-immunized splenocytes. In contrast, [3H]DG uptake by sRBC-immunized splenocytes, co-cultured with macrophages phagocytizing sRBC-AbCs, was about 40 times higher compared with non-immunized splenocytes. Splenocytes in non-immunized mice picked up very little [3H]DG, despite co-culture with macrophages phagocytizing sRBC-AbCs. Similar tendencies were observed with FDG. CONCLUSIONS: These results suggest that the SUV calculated in PET reflects not only the number of lymphocytes, but also the activation state of the lymphocytes themselves. In addition, the biodistribution of antigen specific lymphocytes, that have been taken up FDG in vitro and returned to the body, can be observed through PET.     

Propofol depresses the activity of hypoglossal nerve more than that of phrenic nerve in rabbits

BACKGROUND: Respiratory depression, such as obstruction of upper airway and inadequate ventilation, often appears during sedation and anesthesia. We studied the effect of propofol on the upper airway patency and the inspiratory drives. METHODS: Experiments were performed on the adult rabbits vagotomized, paralyzed and ventilated with nitrous oxide-oxygen-sevoflurane. We evaluated and compared depressant effect of propofol on the peak amplitude of both hypoglossal nerve (AMP-HG) and phrenic nerve (AMP-PH) activities, inspiratory time (Ti), expiratory time (Te) and respiratory cycle (Tc). RESULTS: Bolus injections of propofol transiently reduced AMP-HG more than AMP-PH (18 and 70% of control, respectively). But AMPs returned to the control levels about 10-15 min after the injection. For 0.5 mg.kg-1.min-1 continuous infusion, propofol soon began to reduce both AMPs. AMP-HG was reduced to about 20% and AMP-PH to 60% of control. Administration of propofol with 1.0 mg.kg-1.min-1 caused more reduction in AMPs with respiratory slowing and AMP-HG disappeared in some animals. CONCLUSION: During the sedation with low dose of propofol, we need to pay attention to potential upper airway obstruction. In addition to the above, high doses of propofol could reduce spontaneous inspiratory drive, and we need to keep both upper airway patency and sufficient ventilation.