Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B (NFkappaB) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, NFkappaB activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of NFkappaB activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of NFkappaB and phospho-IkappaB proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of NFkappaB and phospho-IkappaB significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of NFkappaB and phophorylation of IkappaB in the CNS. Subsequently, the inhibition of NFkappaB activation and IkappaB phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.
Animals ; Blood-Brain Barrier ; Central Nervous System ; Cytokines ; Encephalomyelitis, Autoimmune, Experimental ; Humans ; Inflammation ; Mice ; Models, Animal ; Multiple Sclerosis ; Neuroglia ; NF-kappa B ; Peptides ; Phosphorylation ; Proteins ; T-Lymphocytes ; Transcription Factors

PURPOSE: To evaluate the effect of reconstruction algorithms on the CT measurement of mean lung mass density and normal thoracic structures. MATERIALS AND METHODS: Forty-six patients with a 2-9cm-sized lung mass underwent thoracic CT examinations with intravenous contrast enhancement and using a CT HiSpeed Advantage scanner (GE Medical Systems). In each examination, the axial image of the lung mass was reconstructed using soft, standard, detail, and bone algorithms. The mean value and standard deviation of mass density in Hounsfield Units (HU) were measured using ROIs of three different sizes (50 mm2, 200 mm2, and 350 mm2 or more), and the same method was used to measure the density of normal lung, muscle, bone, and vessels. In 21 patients, mass density was also measured on unenhanced and delayed enhanced images and the degree of enhancement was calculated. RESULTS: The average maximum difference in mean mass density in the images of the four different algorithms was less than 1 (range, 0.1 -1.9) HU (ROI size, 350 mm2 or more), 0 -4.2 HU (200 mm 2), and 0.1 -3.6 HU (50mm2). The average maximum difference in the degree of lung mass enhancement was 0.5 -1.2 (range, 0 -1.6 )HU (ROI size, 350 mm2 or more). The mean density of the four normal thoracic structures was highest in images reconstructed with the bone algorithm, though there was no significant difference between the four different algorithms (p = 1.000). CONCLUSION: The measured mean CT density of a lung mass larger than 2 cm does not significantly change according to the reconstruction algorithm used. When using a small ROI, however, the density difference may increase.
Densitometry* ; Humans ; Lung*

Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, highresolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex—a major region in the extended olfactory network—and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years’ duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups’ gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferronicorrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.