These data indicate that diabetes increases BBB permeability via a loss of tight junction proteins, and that increased BBB permeability in diabetes does not result from hyperglycaemia alone. Increased plasma MMP activity is implicated in degradation of BBB tight junction proteins and increased BBB permeability in diabetes. Peripheral MMP activity may present a novel target for protection of the BBB and prevention of neurological complications in diabetes.

I matinib mesylate (Gleevec) therapy remains the standard of care for patients with chronic myelogenous leukemia (CML).3 Designed as a selective competitive inhibitor of the Abelson (ABL) tyrosine kinases (BCR-ABL, v-ABL, c-ABL), this drug leads to growth arrest or apoptosis (1, 2). Imatinib also displays strong activity against the platelet-derived growth factor receptor, c-kit receptor, ABL-related gene, and their fusion proteins (1-3) and thus has also been used for the therapy of gastrointestinal stromal tumors with mutations in c-kit (2).However, the specificity of this molecule may be broader than originally expected, and it is becoming increasingly evident that imatinib also inhibits key tyrosine kinases in immune cells. The exact nature of imatinib effects (activation or suppression) on lymphocytes or dendritic cells remains controversial. Inhibition of CD4 ϩ or CD8 ϩ T cell proliferation and activation by imatinib has been documented (4 -8). Some reports have further highlighted the negative effect of imatinib on the TCR-induced ZAP70 signaling pathway identifying the leukocyte-specific protein tyrosine kinase (Lck) as a potential molecular target (4, 9). Similarly, a negative modulation of dendritic cell (DC) development by imatinib and a down-regulation of their Ag-presenting function have also been described (10 -12). In contrast to these findings, it has been reported that imatinib does not impede the immunogenicity of DC (13) and may enhance their Ag-presenting function (14). Additionally, some reports indicate that imatinib may foster DC-NK reciprocal activation, thereby promoting the antitumoral function of NK cells (15). CD4 ϩ CD25 ϩ regulatory T lymphocytes (Treg) critically contribute to the maintenance of self-tolerance and to the prevention of autoimmunity in animals and humans (16, 17). These suppressive cells have also been highlighted as major contributors in the establishment and persistence of cancer-induced immune tolerance (18,19). Treg expansion detected in the blood, lymph nodes, and spleens of tumor-bearing hosts (20 -23) may result from the conversion of CD4 ϩ CD25 Ϫ T cells into CD4 ϩ CD25 ϩ Treg (24) or from the proliferation of naturally occurring Treg (25). Tumorinduced Treg compromise the function of anti-tumor effector CD8 ϩ T cells, curtail CD4 ϩ T cell help, impede Ag-presenting cell activity (18,23,26) and therefore represent a major obstacle for successful cancer immunotherapy. In support of this concept, studies in humans and in animal models have demonstrated that attempts to disrupt Treg suppressive activity promote antitumoral immunity (20,27,28). Different strategies have thus been evaluated to deplete or inactivate Treg and include the use of anti-CD25 Abs, the IL-2/diphtheria toxin fusion protein, the immunotoxin The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.1 This work was supported in p...

This study compared two established dietary formulations, high salt and high fat-high carbohydrate, separately or in combination on the induction cardiovascular dysfunction. One-month-old C57BL/6J mice were fed one of the following diets for 3 mo: (1) control diet consisting of a high fat-high sim-ple carbohydrate (HFHSC); (2) 8% NaCl diet (HS); or (3) HFHSC diet supplemented with 1% NaCl (HFHS). After 3 mo, the HFHSC mice demonstrated significantly increased end-diastolic volume and end-systolic volume, specifically increases of 35% and 78%, respectively (p < 0.01) and a reduction of ventricular stiffness by 27% (p = 0.015). The HS mice exhibited arterial hyper-tension with an increase of 33% in maximum end-systolic pressure (p =.024) and a decrease of 44% in arterial elastance (p = 0.020), corroborated by an increase in the heart weight to body weight ratios (p = 0.002) and vascular types I and III collagen (p = 0.03 and p = 0.0008, respectively). The HFHS group revealed a striking response of 230% to the alpha1-adrenergic challenge (p = 0.00034). These data suggest that the HFHSC diet causes dilated cardio-myopathy, whereas the HS diet produces arterial hypertension and the HFHS diet causes a vascular dysfunctional state that was highly responsive to alpha-adrenergic stimulation.

Establishing a diagnosis of Alzheimer dementia can be challenging, particularly early in the course of the disease. However, with disease-modifying therapies on the horizon, it is becoming increasingly important to achieve the correct diagnosis as soon as possible. In challenging presentations of dementia, such as patients with clinically atypical features or early-age onset of mild cognitive impairment, amyloid PET is a valuable tool in determining the diagnosis of Alzheimer dementia. Furthermore, preliminary data show that amyloid PET findings alter clinical management in patients who meet the appropriate use criteria. There are currently three U.S. Food and Drug Administration (FDA)-approved fluorine 18 ( 18 F)-labeled radiopharmaceuticals that allow in vivo detection of cerebral amyloid deposition, which is a hallmark pathologic feature of Alzheimer dementia. Knowledge of the common imaging features among these three 18 F-labeled radiopharmaceuticals in the normal and abnormal brain will enable the radiologist to more accurately interpret amyloid PET studies. As in other subspecialties of radiology, imaging signs in amyloid PET are helpful to distinguish if a region is normal or abnormal. This article reviews appropriate use criteria for amyloid PET, introduces the properties of the radiopharmaceuticals, explains the algorithmic approach to interpretation with examples of normal and abnormal amyloid PET scans with MRI correlation, and provides an atlas of regional amyloid PET signs and common artifacts. © RSNA, 2018 •