Interleukin (IL)-1β is involved in physiological sleep regulation. IL-18 is a member of the IL-1 family, and its signal-transduction mechanism is similar to that of IL-1. Therefore, we hypothesized that IL-18 might also be involved in sleep regulation. Three doses of IL-18 (10, 100, and 500 ng) were injected intracerebroventricularly (icv) into rabbits at the onset of the dark period. The two higher doses of IL-18 markedly increased non-rapid eye movement sleep (NREMS), accompanied by increases in brain temperature (Tbr). These effects were lost after the heat inactivation of IL-18. The 500 ng of IL-18 injection during the light period also increased NREMS and Tbr. Similar results were obtained after icv injection of 100 ng of IL-18 into rats. Furthermore, intraperitoneal injection of 30 μg/kg of IL-18 slightly, but significantly, increased NREMS, whereas it significantly decreased electroencephalogram slow-wave activity in rats. Intraperitoneal IL-18 failed to induce fever. An anti-human IL-18 antibody had little effect on spontaneous sleep in rabbits, although the anti-IL-18 antibody significantly attenuated muramyl dipeptide-induced sleep. These data suggest that IL-18 is involved in mechanisms of sleep responses to infection.
Much evidence suggests that tumor necrosis factor-alpha (TNF-alpha) is involved in the regulation of physiological sleep. However, it remains unclear whether peripheral administration of TNF-alpha induces sleep in rats. Furthermore, the role of the vagus nerve in the somnogenic actions of TNF-alpha had not heretofore been studied. Four doses of TNF-alpha were administered intraperitoneally just before the onset of the dark period. The three higher doses of TNF-alpha (50, 100, and 200 microg/kg) dose dependently increased nonrapid eye movement sleep (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave activity. TNF-alpha increased EEG delta-power and decreased EEG alpha- and beta-power during the initial 3 h after injection. In vagotomized rats, the NREMS responses to 50 or 100 microg/kg of TNF-alpha were attenuated, while significant TNF-alpha-induced increases in NREMS were observed in a sham-operated group. Moreover, the vagotomized rats failed to exhibit the increase in EEG delta-power induced by TNF-alpha intraperitoneally. These results suggest that peripheral TNF-alpha can induce NREMS and vagal afferents play an important role in the effects of peripheral TNF-alpha and EEG synchronization on sleep. Intraperitoneal TNF-alpha failed to affect brain temperature at the doses tested, thereby demonstrating that TNF-alpha-induced sleep effects are, in part, independent from its effects on brain temperature. Results are consistent with the hypothesis that a cytokine network is involved in sleep regulation.
Coronary computed tomography angiography (CCTA) has emerged as the preferred modality in the diagnosis of coronary artery disease, but it is limited by modest specificity. By applying principles of computational fluid dynamics, flow fraction reserve, a measure of lesion-specific ischemia that is used to guide revascularization, can be noninvasively derived from CCTA, the so-called computed tomography-derived flow fractional reserve (FFRCT). The accuracy of FFRCT in discriminating ischemia has been extensively validated, and it has been shown to improve the specificity of CCTA. Compared to other stress myocardial perfusion imaging, FFRCT has superior or comparable accuracy. Clinical studies have provided strong evidence that FFRCT has significant prognostic implications and informs clinical decisions for revascularization, serving as a gatekeeper to invasive coronary angiography. In addition, FFRCT-based tools can be used to simulate the physiological consequences of different revascularization strategies, thus providing the roadmap to achieve complete revascularization. Although challenges remain, ongoing research and randomized controlled trials are expected to address current limitations and better define its role in clinical practice.
This chapter examines the effects of the bacterial products known as muramyl peptides on the electroencephalogram (EEG) and fever response in the rat. The mechanism of action of muramyl peptides may be in part represented by the dynamics of the cytokine interleukin-1. In the case of antibiotic-induced slow wave sleep (SWS) reduction, the depletion of bacterial load in the intestine is thought to lower the availability of the bacterial cell wall derivatives known as muramyl peptides. The most specific substrate for the enzyme is NAMP. The observation that NAMP was structurally very similar to other somnogenic muramyl peptides led to investigate the possibility that NAMP was indeed somnogenic. There is a clear shift in the activity of the delta band of the EEG spectrum following administration of NAMP. This increase in delta activity is seen in other muramyl peptide responses and is usually associated with increases in the duration of SWS.
Overuse or degenerative tendon injuries (tendinopathies) are common in sport, certain occupations and even everyday life. They are difficult to treat because of the high failure rate of treatment, tendency towards chronicity and risk of recurrence. (author abstract)
Diffuse, multi vessel coronary artery disease (CAD) affects about one third of patients with CAD and is associated with worse outcomes. Abnormal vascular stiffness and function (e.g., reflected by increased endothelial microparticles and diminished microvascular endothelial-mediated responses), cell mediated pro-inflammatory status (e.g., reflected by levels of specific monocyte subsets), and platelet function (e.g., increased monocyte-platelet aggregates (MPAs) and platelet microparticles) have established roles in CAD pathogenesis but their contribution to the unfavourable diffuse CAD form is unclear. The aim of this study was to compare measures of vascular function, monocyte subsets, MP As, and endothelial and platelet microparticles in patients with diffuse and focal CAD and subjects without CAD. Additionally, prospective changes in these characteristics were analysed over one year. I found increased counts of aggregates of Mon2 monocyte subset with platelets and apoptotic endothelial microparticles in patients with diffuse CAD and I identified a negative correlation between Mon2 MPAs and microvascular endothelial function and increased diastolic elastance. My findings suggest that excessive levels of Mon2 aggregates with platelets and apoptotic endothelial micropa1iicles could be important contributors to the diffuse type of CAD by a mechanism involving microvascular endothelial dysfunction and abnonnal cardio-vascular interactions.
Ulcerative dermatitis (UD) is a common cause of morbidity and euthanasia in mice with a C57BL/6 (B6) background. The purposes of the current study were to determine whether UD lesions could be reliably produced in B6 mice lacking stearoyl-CoA desaturase 1 (SCD1(-/-) mice), to ascertain whether the UD lesions in SCD1(-/-) mice were similar to those found in other B6 mice, and to characterize the cell invasion phenotype of Staphlococcus xylosus cultured from the lesions. S. xylosus isolates from the environment and human skin were used as controls. SCD1(-/-) (n = 8 per group) and nontransgenic B6 control mice (n = 22 mice pooled from 3 groups that received different concentrations of conjugated linoleic acid) were fed standard rodent chow or a semipurified diet (NIH AIN76A) for 4 wk. Samples from other B6 mice with UD (field cases; n = 7) also were submitted for histology and culture. All of the SCD1(-/-) mice developed UD lesions by 4 wk on NIH AIN76A. None of SCD1(-/-) fed standard rodent chow and none of the wildtype B6 mice fed NIH AIN76A developed UD. Supplementation with conjugated linoleic acid did not affect ulcerogenesis. UD lesions in SCD1(-/-) mice and field cases were grossly and histologically similar. S. xylosus was isolated from SCD1(-/-) mice with UD (71%) and field cases of UD (43%). These isolates were the most cell-invasive, followed by the environmental isolate, and finally the human skin isolate. Our results provide a basis for further pathologic and clinical study of UD.
Somatosensory (SSctx) and visual cortex (Vctx) EEG were evaluated in rats under a 12:12-h light-dark (LD) cycle and under constant light (LL) or constant dark (DD) in each sleep or wake state. Under LD conditions during light period, relative Vctx EEG slow-wave activity (SWA) was higher than that of the SSctx, whereas during dark period, relative Vctx EEG SWA was lower than in the SSctx. These effects were state specific, occurring only during non-rapid eye movement sleep (NREMS). Under LL conditions, the duration of REMS and NREMS during the period that would have been dark if the LD cycle had continued (subjective dark period) was greater than under LD conditions. DD conditions had little effect on the duration of NREMS and REMS. SSctx and Vctx EEG SWA were suppressed by LL during the subjective dark period; however, the degree of Vctx SWA suppression was smaller than that of the SSctx. DD conditions during the subjective light period enhanced SSctx SWA, whereas Vctx SWA was suppressed. Under LL conditions during the subjective dark period, Vctx EEG power was higher than that of the SSctx across a broad frequency range during NREMS, REMS, and wakefulness. During DD, SSctx EEG power during NREMS was higher than that of the Vctx in the delta wave band, whereas SSctx power during REMS and wakefulness was higher than that of the Vctx in frequencies higher than 8 Hz. We concluded that the SSctx and Vctx EEGs are differentially affected by light during subsequent sleep. Results provide support for the notion that regional sleep intensity is dependent on prior regional afferent input.
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