Nocturnal secretion of TSH and ACTH in male patients with depression and healthy controls

profound alterations of the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-adrenal (HPA) systems at the hypophyseal level have been described in affective disorder. To precisely characterize the basal alterations of both axes during sleep. we simultaneously investigated sleep EEG and the secretion of thyrotropin. ACTH and cortisol in nine drug-free male patients with depression in comparison to 10 healthy age and sex matched controls. In depressed patients the nearly diametrical nocturnal secretion of thyrotropin and ACTH was disturbed by significantly blunted thyrotropin values (TSH AUC 51.96+/-5.68 vs. 87.23+/-13.63. P<0.05) and elevated ACTH values (ACTH AUC 1804+/-161 vs. 1538+/-130. P<0.05) compared to controls. Moreover, cross correlation analysis revealed a highly negative association of 0 lag between thyrotropin and ACTH and between thyrotropin and cortisol in the control sample, indicating a physiological nocturnal negative correlation of HPT and HPA system. In the patients sample these associations were weak and reached not statistical significance. Therefore, as a descriptive tool, the ratio TSH/ACTH revealed a significant group difference between controls and patients in the first half of the night (TSH/ACTH AUC 6.50+/-0.42 vs. 3.35+/-0.31. P<0.05). Sleep-EEG analysis showed a shortened REM latency, a decrease of stage 2 and an increase of awake time in the patients. Our data support the hypothesis that both hypophyseal hormones reflect a common dysregulation of both systems in depression probably due to impaired action of TRH-related corticotropin-release- inhibiting-factor (CRIF). The ratio TSH/ACTH might be a tool to characterize alterations of both the HPT and HPA axis in depression during the first half of the night, (C), 2002 Elsevier Science Ltd. All rights reserv

J. Psychiatr. Res.

profound alterations of the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-adrenal (HPA) systems at the hypophyseal level have been described in affective disorder. To precisely characterize the basal alterations of both axes during sleep. we simultaneously investigated sleep EEG and the secretion of thyrotropin. ACTH and cortisol in nine drug-free male patients with depression in comparison to 10 healthy age and sex matched controls. In depressed patients the nearly diametrical nocturnal secretion of thyrotropin and ACTH was disturbed by significantly blunted thyrotropin values (TSH AUC 51.96+/-5.68 vs. 87.23+/-13.63. P<0.05) and elevated ACTH values (ACTH AUC 1804+/-161 vs. 1538+/-130. P<0.05) compared to controls. Moreover, cross correlation analysis revealed a highly negative association of 0 lag between thyrotropin and ACTH and between thyrotropin and cortisol in the control sample, indicating a physiological nocturnal negative correlation of HPT and HPA system. In the patients sample these associations were weak and reached not statistical significance. Therefore, as a descriptive tool, the ratio TSH/ACTH revealed a significant group difference between controls and patients in the first half of the night (TSH/ACTH AUC 6.50+/-0.42 vs. 3.35+/-0.31. P<0.05). Sleep-EEG analysis showed a shortened REM latency, a decrease of stage 2 and an increase of awake time in the patients. Our data support the hypothesis that both hypophyseal hormones reflect a common dysregulation of both systems in depression probably due to impaired action of TRH-related corticotropin-release- inhibiting-factor (CRIF). The ratio TSH/ACTH might be a tool to characterize alterations of both the HPT and HPA axis in depression during the first half of the night, (C), 2002 Elsevier Science Ltd. All rights reserv

Solution structure of the antitermination protein NusB of Escherichia coli: a novel all-helical fold for an RNA-binding protein.

The NusB protein of Escherichia coli is involved in the regulation of rRNA biosynthesis by transcriptional antitermination. In cooperation with several other proteins, it binds to a dodecamer motif designated rrn boxA on the nascent rRNA. The antitermination proteins of E.coli are recruited in the replication cycle of bacteriophage lambda, where they play an important role in switching from the lysogenic to the lytic cycle. Multidimensional heteronuclear NMR experiments were performed with recombinant NusB protein labelled with 13C, 15N and 2H. The three-dimensional structure of the protein was solved from 1926 NMR-derived distances and 80 torsion angle restraints. The protein folds into an alpha/alpha-helical topology consisting of six helices; the arginine-rich N-terminus appears to be disordered. Complexation of the protein with an RNA dodecamer equivalent to the rrn boxA site results in chemical shift changes of numerous amide signals. The overall packing of the protein appears to be conserved, but the flexible N-terminus adopts a more rigid structure upon RNA binding, indicating that the N-terminus functions as an arginine-rich RNA-binding motif (ARM)

Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection

Influenza A viruses (IAV) can cause lung injury and acute respiratory distress syndrome (ARDS), which is characterized by accumulation of excessive fluid (edema) in the alveolar airspaces and leads to hypoxemia and death if not corrected. Clearance of excess edema fluid is driven mostly by the alveolar epithelial Na,K-ATPase and is crucial for survival of patients with ARDS. We therefore investigated whether IAV infection alters Na,K-ATPase expression and function in alveolar epithelial cells (AECs) and the ability of the lung to clear edema. IAV infection reduced Na,K-ATPase in the plasma membrane of human and murine AECs and in distal lung epithelium of infected mice. Moreover, induced Na,K-ATPase improved alveolar fluid clearance (AFC) in IAV-infected mice. We identified a paracrine cell communication network between infected and noninfected AECs and alveolar macrophages that leads to decreased alveolar epithelial Na,K-ATPase function and plasma membrane abundance and inhibition of AFC. We determined that the IAV-induced reduction of Na,K-ATPase is mediated by a host signaling pathway that involves epithelial type I IFN and an IFN-dependent elevation of macrophage TNF-related apoptosis-inducing ligand (TRAIL). Our data reveal that interruption of this cellular crosstalk improves edema resolution, which is of biologic and clinical importance to patients with IAV-induced lung injury