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Years and Volumes

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Molecular Medicine Volume 9
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Articles from this Volume

Alex E Roher, Yu-Min Kuo, Chera Esh, Carmen Knebel, Nicole Weiss, Walter Kalback, Dean C Luehrs, Jennifer L Childress, Thomas G Beach, Roy O Weller, and Tyler A Kokjohn

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and by the accumulation of β-amyloid (Aβ) peptides in senile plaques and in the walls of cortical and leptomeningeal arteries as cerebral amyloid angiopathy (CAA). There also is a significant increase of interstitial fluid (ISF) in cerebral white matter (WM), the pathological basis of which is largely unknown. We hypothesized that the accumulation of ISF in dilated periarterial spaces of the WM in AD correlates with the severity of CAA, with the total Aβ load in the cortex and with Apo E genotype. A total of 24 AD brains and 17 nondemented age-matched control brains were examined. CAA was seen in vessels isolated from brain by using EDTA-SDS lysis stained by Thioflavin-S. Total Aβ in gray matter and WM was quantified by immunoassay, ApoE genotyping by PCR, and dilatation of perivascular spaces in the WM was assessed by quantitative histology. The study showed that the frequency and severity of dilatation of perivascular spaces in the WM in AD were significantly greater than in controls (P < 0.001) and correlated with Aβ load in the cortex, with the severity of CAA, and with ApoE ε4 genotype. The results of this study suggest that dilation of perivascular spaces and failure of drainage of ISF from the WM in AD may be associated with the deposition of Aβ in the perivascular fluid drainage pathways of cortical and leptomeningeal arteries. This failure of fluid drainage has implications for therapeutic strategies to treat Alzheimer’s disease. 

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Posted by Leah Caracappa on Mar 6, 2003 12:00 AM CST
Donatella Vincenti, Stefania Carrara, Patrizia De Mori, Leopoldo P Pucillo, Nicola Petrosillo, Fabrizio Palmieri, Orlando Armignacco, Giuseppe Ippolito, Enrico Girardi, Massimo Amicosante, and Delia Goletti

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Posted by Leah Caracappa on Mar 5, 2003 12:00 AM CST
Jon G Mabley, Alex Rabinovitch, Wilma Suarez-Pinzon, György Haskó, Pál Pacher, Robert Power, Gary Southan, Andrew Salzman, and Csaba Szabó

Inosine, a naturally occurring purine, was long considered to be an inactive metabolite of adenosine. However, recently inosine has been shown to be an immunomodulator and anti-inflammatory agent. The aim of this study was to determine whether inosine influences anti-inflammatory effects and affects the development of type 1 diabetes in murine models. Type 1 diabetes was induced either chemically by streptozotocin or genetically using the nonobese diabetic mouse (NOD) model. Mice were treated with inosine (100 or 200 mg kg–1d–1) and diabetes incidence was monitored. The effect of inosine on pancreas immune cell infiltration, oxidative stress, and cytokine profile also was determined. For the transplantation model islets were placed under the renal capsule of NOD mice and inosine (200 mg kg–1d–1) treatment started the day of islet transplantation. Graft rejection was diagnosed by return of hyperglycemia accompanied by glucosuria and ketonuria. Inosine reduced the incidence of diabetes in both streptozotocin-induced diabetes and spontaneous diabetes in NOD mice. Inosine decreased pancreatic leukocyte infiltration and oxidative stress in addition to switching the cytokine profile from a Th1 to a Th2 profile. Inosine prolonged pancreatic islet graft survival, increased the number of surviving β cells, and reduced the number of infiltrating leukocytes. Inosine protects against both the development of diabetes and against the rejection of transplanted islets. The purine exerts anti-inflammatory effects in the pancreas, which is its likely mode of action. The use of inosine should be considered as a potential preventative therapy in humans susceptible to developing Type 1 diabetes and as a possible antirejection therapy for islet transplant recipients. 

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Posted by Leah Caracappa on Mar 4, 2003 12:00 AM CST
Ines Schwering, Andreas Bräuninger, Verena Distler, Julia Jesdinsky, Volker Diehl, Martin-Leo Hansmann, Klaus Rajewsky, and Ralf Küppers

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Posted by Leah Caracappa on Mar 3, 2003 12:00 AM CST
Posted by Leah Caracappa on Mar 2, 2003 12:00 AM CST
Chao-Wen Wang and Daniel J Klionsky

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Posted by Leah Caracappa on Mar 1, 2003 12:00 AM CST