Prediction of mild cognitive impairment that evolves into Alzheimer's disease dementia within two years using a gene expression signature in blood: a pilot study.

BACKGROUND: The focus on Alzheimer's disease (AD) is shifting from dementia to the prodromal stage of the disorder, to a large extent due to increasing efforts in trying to develop disease modifying treatment for the disorder. For development of disease-modifying drugs, a reliable and accurate test for identification of mild cognitive impairment (MCI) due to AD is essential. OBJECTIVE: In the present study, MCI progressing to AD will be predicted using blood-based gene expression. MATERIAL AND METHODS: Gene expression analysis using qPCR was performed on blood RNA from a cohort of patients with amnestic MCI (aMCI; n = 66). Within the aMCI cohort, patients progressing to AD within 1 to 2 years were grouped as MCI converters (n = 34) and the patients remaining at the MCI stage after 2 years were grouped as stable MCI (n = 32). AD and control populations were also included in the study. RESULTS: Multivariate statistical method partial least square regression was used to develop predictive models which later were tested using leave-one-out cross validation. Gene expression signatures that identified aMCI subjects that progressed to AD within 2 years with a prediction accuracy of 74%-77% were identified for the complete dataset and subsets thereof. CONCLUSION: The present pilot study demonstrates for the first time that MCI that evolves into AD dementia within 2 years may be predicted by analyzing gene expression in blood. Further studies will be needed to validate this gene signature as a potential test for AD in the predementia stage.

Size-biased allocation of prey from male to offspring via female: family conflicts, prey selection, and evolution of sexual size dimorphism in raptors.

In birds with bi-parental care, the provisioning link between prey capture and delivery to dependent offspring is regarded as often symmetric between the mates. However, in raptors, the larger female usually broods and feeds the nestlings, while the smaller male provides food for the family, assisted by the female in the latter part of the nestling period, if at all. Prey items are relatively large and often impossible for nestlings to handle without extended maternal assistance. We video-recorded prey delivery and handling in nests of a raptor with a wide diet, the Eurasian kestrel Falco tinnunculus, and simultaneously observed prey transfer from male to female outside the nest. The male selectively allocated larger items, in particular birds and larger mammals, to the female for further processing and feeding of nestlings, and smaller items, in particular lizards and smaller mammals, directly to the nestlings for unassisted feeding. Hence, from the video, the female appeared to have captured larger prey than the male, while in reality no difference existed. The female's size-biased interception of the male's prey provisioning line would maximize the male's foraging time, and maximize the female's control of the allocation of food between her own need and that of the offspring. The male would maximize his control of food allocation by capturing smaller prey. This conflict would select for larger dominant females and smaller energy-efficient males, and induce stronger selection the longer the female depends on the male for self-feeding, as a proportion of the offspring dependence period.

GE-145, a new low-osmolar dimeric radiographic contrast medium.

BACKGROUND: Contrast-induced nephrotoxicity is a significant risk when using radiographic contrast media clinically, especially in high risk patients. Consequently, there is a need for a new contrast agent with improved clinical safety with regards to nephrotoxicity. PURPOSE: To evaluate the physicochemical properties as well as the preclinical safety and biodistribution parameters of the newly developed radiographic contrast medium GE-145. MATERIAL AND METHODS: Standard methods for radiographic contrast media were used for evaluation of physicochemical properties. The acute toxicity in rats was studied at 8, 10, and 12.5 gI/kg, the clinical chemistry parameters were determined, and histology of the kidneys was performed. Biodistribution was studied in rats using ¹²³I-labeled GE-145. RESULTS: GE-145 is more hydrophilic than iodixanol and has a considerably lower osmolality. The viscosity is similar to that of iodixanol and the protein binding is low. The acute toxicity is similar to that of iodixanol and the biodistribution is similar to that of other radiographic contrast media, showing mainly renal excretion. Kidney histology showed a moderate reversible vacuolization, similar to that of iodixanol. CONCLUSION: GE-145 exhibits similar preclinical properties to other dimeric radiographic contrast media. In addition, the low osmolality enables an iso-osmolar formulation containing a significantly higher concentration of electrolytes than Visipaque.

Quantification of NC100692, a new tracer for 99mTc-imaging of angiogenesis, in human plasma using reversed-phase liquid chromatography coupled with electrospray ionization ion-trap mass spectrometry.

NC100692 is under development as a diagnostic radiopharmaceutical for targeting angiogenesis associated with diseases, such as cancer and endometriosis. NC100692 consists of a cyclic RGD-containing peptide with an ethylene glycol chain linked to the C-terminal amino acid and a (99m)Tc-binding chelator linked to the N-terminal amino acid. The present report describes a method for quantification of NC100692 in human citrated plasma. The method is based on solid-phase extraction followed by reversed-phase liquid chromatography using a gradient of water and acetonitrile with 0.1% formic acid. The chromatographic system was coupled on-line with an electrospray mass spectrometer. The analyses were performed by selective ion monitoring of the [M+2H](2+) and the [M+3H](3+) ions of NC100692 and the internal standard, which was identical to NC100692 except for containing twice the length of the ethyleneglycol chain. The limit of quantification of the method was 0.5 ng NC100692/ml plasma. The calibration curve ranged from 0.5 to 250 ng NC100692/ml plasma and was fitted to a quadratic equation with a weighing factor of 1/y and found to be highly reproducible. The total precision of the method, expressed as the relative standard error of the mean, was 11.1, 10.8 and 9.7% for the low, medium and high control samples, respectively. The accuracy of the method was 103.4, 111.1 and 107.5% for the low, medium and high control samples, respectively. NC100692 was stable in human plasma during at least 3 freeze/thaw cycles, during 48 h on dry ice and at least 8 weeks when stored in a -20 degrees C freezer.