Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A), a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography

Dynamic contrast-enhanced magnetic resonance imaging has been recently shown to be effective for diagnostic urography. High-resolution urographic images can be acquired with T1 contrast agents for the kidney and urinary tract with minimal noise in the abdomen. Currently, clinical contrast agents are low molecular weight agents and can rapidly extravasate from blood circulation, leading to slow contrast agent elimination through kidney and consequently providing limited contrast enhancement in urinary tract. In this study, a new biodegradable macromolecular contrast agent, nanoglobule-G4-cystamine-(Gd-DO3A), was prepared by conjugating Gd-DO3A chelates on the surface of a generation 4 nanoglobule, poly-l-lysine octa(3-aminopropyl)silsesquioxane dendrimer, via a disulfide spacer, where the carrier had a precisely defined nanosize that is far smaller than the renal filtration threshold. The in vivo contrast enhancement and dynamic imaging of the urinary tract of the agent was evaluated in nude mice using a low molecular weight agent Gd(DTPA-BMA) as a control. The agent eliminated rapidly from blood circulation and accumulated more abundantly in urinary tract than Gd(DTPA-BMA). The fast elimination kinetics is ideal for functional evaluation of the kidneys. The morphology of the kidneys and urinary tract was better visualized by the biodegradable nanoglobular contrast agent than Gd(DTPA-BMA). The agent also resulted in low liver contrast enhancement, indicating low nonspecific tissue deposition. These features render the G4 nanoglobule-cystamine-(Gd-DO3A) conjugate a promising contrast agent for magnetic resonance urography

Relationships between 24-Hour Blood Pressures, Subcortical Ischemic Lesions, and Cognitive Impairment

Background and Purpose The most important treatment for subcortical vascular dementia (SVaD) is controlling the blood pressure (BP). However, the few studies that have investigated the relationships between diurnal BP rhythm and subcortical ischemic vascular cognitive impairment have produced inconclusive results. In the study presented here, the 24-hour BP values of three groups of subjects-patients with subcortical vascular mild cognitive impairment (SvMCI), patients with SVaD, and normal controls-were compared using working criteria and 24-hour ambulatory BP (ABP) monitoring. Methods The subjects (42 patients with SVaD, 37 patients with SvMCI, and 30 controls) were selected according to the Study`s inclusion/exclusion criteria. All subjects underwent brain magnetic resonance (MR) imaging and MR angiography, detailed neuropsychological testing, and 24-hour ABP monitoring. Results The prevalence of nondippers differed markedly between the control group and both the SVaD and SvMCI groups. Loss of nocturnal dipping was significantly associated with SVaD [odds ratio (OR), 4.827; 95% confidence interval (CI), 1.07-12.05]. Conclusions It was found that SVaD is associated with loss of nocturnal BP dipping combined with increased pulse pressure and systolic BP (SBP) variability. Correction of these factors could therefore be important in the prevention of SVaD, independent of measures used to reduce BP. J Clin Neurol 2009;5:139-145Ohmine T, 2008, HYPERTENS RES, V31, P75van Boxtel MPJ, 2006, J HUM HYPERTENS, V20, P5, DOI 10.1038/sj.jhh.1001934van der Flier WM, 2005, STROKE, V36, P2116Birns J, 2005, STROKE, V36, P1308, DOI 10.1161/01.STR.0000165901.38039.5fYamamoto Y, 2005, CEREBROVASC DIS, V19, P302, DOI 10.1159/000084498BOWLER JV, 2005, J NEUROL NEUROSUR S5, V76, P35KU HM, 2004, J KOREAN NEUROPSYCHI, V43, P189O`Brien E, 2003, J HYPERTENS, V21, P821, DOI 10.1097/01.hjh.0000059016.82022.caKANG Y, 2003, INCHEON HUMAN BRAINOhkubo T, 2002, J HYPERTENS, V20, P2183de Leeuw FE, 2002, BRAIN, V125, P765O`Brien JT, 2002, ANN NY ACAD SCI, V977, P436Kario K, 2001, HYPERTENSION, V38, P852Wahlund LO, 2001, STROKE, V32, P1318Dufouil C, 2001, NEUROLOGY, V56, P921Puisieux F, 2001, EUR NEUROL, V46, P115Staessen JA, 1999, JAMA-J AM MED ASSOC, V282, P539Swan GE, 1998, NEUROLOGY, V51, P986Blacher J, 1998, HYPERTENSION, V32, P570Cummings JL, 1998, J PSYCHOSOM RES, V44, P627Kilander L, 1998, HYPERTENSION, V31, P780Guo ZC, 1997, AM J EPIDEMIOL, V145, P1106Liao DP, 1996, STROKE, V27, P2262LAUNER LJ, 1995, JAMA-J AM MED ASSOC, V274, P1846YAMAMOTO Y, 1995, STROKE, V26, P829VERDECCHIA P, 1994, HYPERTENSION, V24, P793KUUSISTO J, 1993, HYPERTENSION, V22, P771SHIMADA K, 1992, J HYPERTENS, V10, P875SCHERR PA, 1991, AM J EPIDEMIOL, V134, P1303TOHGI H, 1991, STROKE, V22, P603OBRIEN E, 1988, LANCET, V2, P397PARATI G, 1987, J HYPERTENS, V5, P93HACHINSKI VC, 1975, ARCH NEUROL-CHICAGO, V32, P632