Cell layers and neuropil: contrast‐enhanced MRI of mouse brain in vivo

Contrast‐enhanced T₁‐ and T₂‐weighted MRI at 9.4 T and in‐plane resolutions of 25 and 30 µm has been demonstrated to differentiate between neural tissues in mouse brain in vivo, including granule cell layers, principal cell layers, general neuropil, specialized neuropil and white matter. In T₁‐weighted MRI of the olfactory bulb, hippocampus and cerebellum, contrast obtained by the intracranial administration of gadopentetate dimeglumine (Gd‐DTPA) reflects the extra‐ and intracellular spaces of gray matter in agreement with histological data. General neuropil areas are highlighted, whereas other tissues present with lower signal intensities. The induced contrast is similar to that in plain T₂‐weighted MRI, but offers a 16–30‐fold higher contrast‐to‐noise ratio. Systemic administration of manganese chloride increases the signal‐to‐noise ratio in T₁‐weighted MRI to a significantly greater extent in principal cell layers and specialized neuropil than in granule cell layers, whereas gadolinium‐enhanced MRI indicates no larger intracellular spaces in these tissues. Granule cell layers are enhanced no more than general neuropil by manganese, whereas gadolinium‐enhanced MRI indicates significantly larger intracellular spaces in the cell layers. These discrepancies suggest that the signal increase after manganese administration reflects cellular activity which is disproportionate to the intracellular space. As a result, principal cell layers and specialized neuropil become highlighted, whereas granule cell layers, general neuropil and white matter present with lower signal intensities. Copyright © 2013 John Wiley & Sons, Ltd.     

Immunotoxicologic effects of cyclosporine on tumor progression in models of squamous cell carcinoma and B-cell lymphoma in C3H mice

Many immunosuppressive drugs are associated with an increased risk of neoplasia, principally non-melanoma skin cancers and B-cell lymphomas. However, only 6 of the 13 immunosuppressive drugs tested in 2 year bioassays increased the incidence of neoplasia. For example, the 2-year bioassays conducted with cyclosporine (CSA), an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, were negative. The purpose of these investigations was to use transplanted tumor models in immunocompetent, syngeneic mice to gain insight into the failure of the 2-year bioassay to show an increased incidence of neoplasia with CSA. C3H HeN mice were used in a battery of assays with a transplanted squamous cell carcinoma (SCC VII cells) or a B-cell, lymphoma (38C13 cells) cells to study effects of CSA on local growth and metastases, experimental metastases, and progression of established metastases. Mice received CSA twice weekly by subcutaneous (SC) injection at doses of 0.5, 5, or 50?mg/kg; controls received the CSA vehicle. CSA had a modest inhibitory effect on SC tumors initiated by 38C13 cells and on intramuscular tumors initiated by SCC VII cells. CSA also decreased the number of lung colonies and decreased the size, growth fraction and vascularity of established lung metastases initiated by SCC VII cells. In contrast, CSA increased progressive growth of metastases to the sentinel lymph node from an intramuscular SCC VII tumor, but had no effect cellular traffic to the node. In conclusion, CSA at doses up to 50?mg/kg did not facilitate tumor progression and it partially inhibited tumor growth, suggesting that suppression of tumor progression may partially explain the failure of CSA to act as a carcinogen in 2 year bioassays.     

【In Press】 Protective effect of pomegranate juice on retinal oxidative stress in streptozotocin-induced diabetic rats

AIM: To investigate the effect of pomegranate juice (PJ) intake on overall oxidation status in retinas of diabetic rats. METHODS: Twenty-seven rats were divided into four groups as control (CO), diabetic (DM), control treated with PC (CO-PJ), and diabetic treated with PJ (DM-PJ).The retina tissues were used to determine 8-Hydroxy-2’-deoxyguanosine (8OHdG), malondialdehyde (MDA), reduced glutathione (GSH) levels, and the enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). RESULTS: The levels of 8OHdG and MDA were significantly increased in the retina of DM group compared to CO group (p=0.001, p<0.001 respectively). Both 8OHdG and MDA levels were decreased in PJ-DM group compared to DM group (p=0.004, p<0.001 respectively). The activities of antioxidant enzymes GSH, SOD, and GDH-Px were significantly decreased in the retina of DM group compared to CO group (p≤0.01). GSH and GSH-Px activities were higher in PJ-DM group compared with DM group (p=0.010, p=0.042, respectively) but SOD activity was not statistically different (p=0.938). CONCLUSION: PJ intake was found to be effective in decreasing oxidative end products, and in increasing the activities of antioxidant enzymes in diabetic retinas of rats, which suggests it may be effective against oxidative stress in diabetic retinas.     

Therapeutic efficacy of intense pulsed light in patients with refractory meibomian gland dysfunction

Purpose

To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for treatment of refractory meibomian gland dysfunction (MGD).