High-resolution magnetization transfer MRI in patients with cervical spondylotic myelopathy.

Magnetization transfer (MT) contrast has been established as a marker of myelin integrity, and cervical spondylotic myelopathy is known to cause demyelination. Ten patients with clinical and magnetic resonance imaging (MRI) manifestations of cervical spondylotic myelopathy (CSM) were compared to the MRIs of seven historic healthy controls, using the magnetization transfer ratio (MTR) and Nurick scores as the primary metrics. Transverse slices through the intervertebral discs of the cervical spine were acquired using a gradient echo sequence (MEDIC) with and without an MT saturation pulse on a 3 Tesla Siemens Prisma scanner (TR = 300 ms, TEeff = 17 ms, flip angle = 30°, in-plane resolution = 0.47 × 0.47 mm2). The CSM patients tended to have a lower mean MTR (30.4 ±â€¯6.5) than the controls (34.8 ±â€¯3.8), but the difference was not significant (independent samples t-test, p = 0.110, Cohen's d = 0.80). The mean MTR across all intervertebral disc levels was not significantly correlated to the Nurick score (Spearman's ρ = -0.489, p = 0.151). The intervertebral level with the lowest MTR in each cohort was not significantly different between groups (equal variances not assumed, t = 1.965, dof = 14.8, p = 0.068, Cohen's d = 0.88), but the CSM patients tended to have a lower MTR. The mean MTR at this level was negatively correlated to the Nurick score among CSM patients (Spearman's ρ = -0.725, p = 0.018). CSM patients tended to have decreased MTR indicating myelin degradation compared to our healthy subjects, and MTR was negatively correlated with the severity of CSM.

Estrogen receptor activation reduces lipid synthesis in pancreatic islets and prevents ß cell failure in rodent models of type 2 diabetes.

The failure of pancreatic ß cells to adapt to an increasing demand for insulin is the major mechanism by which patients progress from insulin resistance to type 2 diabetes (T2D) and is thought to be related to dysfunctional lipid homeostasis within those cells. In multiple animal models of diabetes, females demonstrate relative protection from ß cell failure. We previously found that the hormone 17ß-estradiol (E2) in part mediates this benefit. Here, we show that treating male Zucker diabetic fatty (ZDF) rats with E2 suppressed synthesis and accumulation of fatty acids and glycerolipids in islets and protected against ß cell failure. The antilipogenic actions of E2 were recapitulated by pharmacological activation of estrogen receptor α (ERα) or ERß in a rat ß cell line and in cultured ZDF rat, mouse, and human islets. Pancreas-specific null deletion of ERα in mice (PERα-/-) prevented reduction of lipid synthesis by E2 via a direct action in islets, and PERα-/- mice were predisposed to islet lipid accumulation and ß cell dysfunction in response to feeding with a high-fat diet. ER activation inhibited ß cell lipid synthesis by suppressing the expression (and activity) of fatty acid synthase via a nonclassical pathway dependent on activated Stat3. Accordingly, pancreas-specific deletion of Stat3 in mice curtailed ER-mediated suppression of lipid synthesis. These data suggest that extranuclear ERs may be promising therapeutic targets to prevent ß cell failure in T2D.