Ectopic insulinoma in a dog with insulin-induced hypoglycemia: a case report

A 7-year-old spayed female Shih Tzu dog was presented for evaluation of recurrent hypoglycemia. Serum insulin levels during hypoglycemia were 35.3 μIU/mL. Ultrasonography and computed tomography showed a mesenteric nodule between the kidney and the portal vein, but no pancreatic mass was observed. During surgery, the nodule had neither anatomical adhesions nor vascular connections to the pancreas. Pancreatic inspection and palpation revealed no abnormalities. Hypoglycemia improved after resection of the nodule.Histopathological examination confirmed the nodule to be an islet cell carcinoma. Although extremely rare, ectopic insulinoma should be considered as a possible cause of insulininduced hypoglycemia in dogs.

Cognitive Impairments in Clinically Stable Late-Life Depression : Relationship to Cardiovascular Risk : A Pilot Study

OBJECTIVE: The purpose of this study was to test the hypothesis that cardiovascular risk is associated with cognitive impairments in clinically stable late-life depression. METHODS: A total of 59 clinically stable late-life depression patients over age 60 were enrolled in a cross-sectional study. Evaluation tools used in this study include Hamilton Rating Scale for Depression, Geriatric Depression Scale, State-Trait Anxiety Inventory, the Framingham general cardiovascular disease risk profile and the cognitive function battery designed for this study. Correlation analysis, analysis of variance and analysis of covariance were performed. RESULTS: Patients with higher cardiovascular risk performed significantly poorer in the domains of executive function and short-term or long-term memory. In models adjusted for age, sex, education, 10% higher cardiovascular risk was associated with poorer executive function. CONCLUSION: Our findings suggested that cardiovascular risk could be a significant factor associated with poor executive function in clinically stable late-life depression and the management which is necessary as a component of treatment planning. This pilot study provided good prospects for future studies to document this relationship on larger samples.

The expression of Foxp3 protein by retroviral vector-mediated gene transfer of Foxp3 in C57BL/6 mice / 대한수의학회지

The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require CD4+CD25+ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both CD4+CD25+ T cell and CD4+Foxp3+ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of CD4+CD25+ T cell and CD4+Foxp3+ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.

Glatiramer acetate inhibits the activation of NFkappaB in the CNS of experimental autoimmune encephalomyelitis / 대한수의학회지

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.

Overexpression of Galectin-3 in Macrophages of C57BL/6 mice with Experimental Autoimmune Encephalomyelitis / 대한수의학회지

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and has long been used as an animal model for human multiple sclerosis. Development of EAE requires coordinated expression of a number of genes that are involved in the activation and effector functions of inflammatory cells. Galectin-3 (Gal-3) is a member of the beta-galactoside-binding lectin family and plays an important role in inflammatory responses through its functions on cell activation, cell migration or inhibition of apoptosis. We investigated the functional role of Gal-3 in EAE mice following immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. During the peak stage of EAE, the localization of Gal-3 in inflammatory cells markedly increased in subarachnoid membranes and perivascular regions of CNS. In contrast, Gal-3 was weakly detected in cerebrum and spinal of the recovery stage of EAE. Consistent with this finding, western blot analysis revealed that Gal-3 expression was significantly increased at the peak stage while it was slightly decreased at the recovery stage in the CNS. In addition, the population of CD11b+ macrophage expressing Gal-3 in spleen of EAE mice was markedly increased compared with control mice. In fact, most of activated macrophages isolated from spleen of EAE mice expressed Gal-3. Taken together, our results demonstrate that the over-expression of Gal-3 in activated macrophages may play a key role in promoting inflammatory cells in the CNS during EAE.