Plasma total prion protein as a potential biomarker for neurodegenerative dementia: diagnostic accuracy in the spectrum of prion diseases.

AIMS: In the search for blood-based biomarkers of neurodegenerative diseases, we characterized the concentration of total prion protein (t-PrP) in the plasma of neurodegenerative dementias. We aimed to assess its accuracy in this differential diagnostic context. METHODS: Plasma t-PrP was measured in 520 individuals including healthy controls (HC) and patients diagnosed with neurological disease control (ND), Alzheimer's disease (AD), sporadic Creutzfeldt-Jakob disease (sCJD), frontotemporal dementia (FTD), Lewy body dementia (LBD) and vascular dementia (VaD). Additionally, t-PrP was quantified in genetic prion diseases and iatrogenic CJD. The accuracy of t-PrP discriminating the diagnostic groups was evaluated and correlated with demographic, genetic and clinical data in prion diseases. Markers of blood-brain barrier impairment were investigated in sCJD brains. RESULTS: Compared to HC and ND, elevated plasma t-PrP concentrations were detected in sCJD, followed by FTD, AD, VaD and LBD. In sCJD, t-PrP was associated neither with age nor sex, but with codon 129 PRNP genotype. Plasma t-PrP concentrations correlated with cerebrospinal fluid (CSF) markers of neuro-axonal damage, but not with CSF t-PrP. In genetic prion diseases, plasma t-PrP was elevated in all type of mutations investigated. In sCJD brain tissue, extravasation of immunoglobulin G and the presence of swollen astrocytic end-feet around the vessels suggested leakage of blood-brain barrier as a potential source of increased plasma t-PrP. CONCLUSIONS: Plasma t-PrP is elevated in prion diseases regardless of aetiology. This pilot study opens the possibility to consider plasma t-PrP as a promising blood-based biomarker in the diagnostic of prion disease.

Radial Photonic Crystal for detection of frequency and position of radiation sources.

Based on the concepts of artificially microstructured materials, i.e. metamaterials, we present here the first practical realization of a radial wave crystal. This type of device was introduced as a theoretical proposal in the field of acoustics, and can be briefly defined as a structured medium with radial symmetry, where the constitutive parameters are invariant under radial geometrical translations. Our practical demonstration is realized in the electromagnetic microwave spectrum, because of the equivalence between the wave problems in both fields. A device has been designed, fabricated and experimentally characterized. It is able to perform beam shaping of punctual wave sources, and also to sense position and frequency of external radiators. Owing to the flexibility offered by the design concept, other possible applications are discussed.

Living donor renal transplantation: prognostic factors on graft survival.

INTRODUCTION: Living donor renal transplantation is a treatment option for patients on dialysis in view of the ever-growing transplantation waiting lists and the stagnation in the number of deceased donors. OBJECTIVES: The objectives of this study were to provide retrospective review of our living donor kidney transplantation series (1978-2003) and analysis of graft survival prognostic factors. MATERIALS AND METHODS: Among 121 living donor transplantations, the donor mean age was 50.9 years (SD, 1.53) and recipient mean age was 30.4 years (SD, 1.4). Eighty-eight percent of donors were women, 90% were related: siblings 21%, parents 69%, and spouses 6.6%. Kidney failure was of nephrological etiology in 65% of patients and urologic in 15.6%. Eighty-four percent were primary grafts and 16% were second ones. Also, 66.7% of kidneys were placed in the iliac fossa and the rest were left orthotopic approaches. Other analyzed variables included donor gender, acute rejection episodes (ARE), creatinine levels at 1 and 6 months, hypertension (HT), and pediatric recipients. RESULTS: Univariate analysis (Kaplan-Meier) showed that, in patients suffering from ARE or not, the mean graft survival was 7.5 and 15 years, respectively (P <.05). Mean graft survival among patients with nephrological problems was 8 years and in those with urologic etiology 15 years (P < .05). Multivariate analysis with Cox regression showed that etiology, ARE, and creatinine level at 6 months after transplantation were independent prognostic variables for graft failure. The overall graft survival rates were 78% at 5 years, 58% at 10 years, 42% at 15 years, and 24% at 20 years follow-up. CONCLUSION: Living donor kidney transplantation is a valid treatment choice for end-stage patients with excellent graft survival rates, especially in cases of urologic etiology. Development of new immunosupressant strategies will help improve outcomes.

Elderly donor kidney transplant: factors involved in graft survival.

PURPOSE: To evaluate whether control of risk factors associated with worse results has improved graft survival, with respect of renal function quality and other factors influencing graft survival: recipient age, immunosuppressive therapy, cold ischemia time, acute tubular necrosis (ATN), acute rejection episodes (ARE) and 1-month creatinine levels. MATERIALS AND METHODS: Retrospective review of 147 patients who underwent kidney transplant between 1995 and 2001. Inclusion criteria were donor and recipient age older than 60 years, first renal transplant, follow-up period longer than 12 months, donor creatinine clearance higher than 75 mL/min, and less than 20% glomerulosclerosis observed in donor renal biopsy. RESULTS: Graft survivals were 87%, 83%, 78%, and 70% at first, second, third, and fifth year after transplantation, respectively. Mean serum creatinine levels were 2.3 mg/dL and mean follow-up time, 46 months. Multivariate analysis using a Cox regression model identified donor age, ARE, and serum creatinine levels 1 month after surgery as independent variables affecting graft survival. Recipient age, immunosuppressive therapy, and serum creatinine levels at 1 month after surgery were predictive variables of recipient survival. DISCUSSION: Renal transplantation is an accepted therapeutic option in elderly patients with chronic renal insufficiency, if both donor and recipient are carefully selected.

Picoliter-scale protein microarrays by laser direct write.

We demonstrate the accurate picoliter-scale dispensing of active proteins using a novel laser transfer technique. Droplets of protein solution are dispensed onto functionalized glass slides and into plastic microwells, activating as small as 50-microm diameter areas on these surfaces. Protein microarrays fabricated by laser transfer were assayed using standard fluorescent labeling techniques to demonstrate successful protein and antigen binding. These results indicate that laser transfer does not damage the active site of the dispensed protein and that this technique can be used to successfully fabricate a functioning protein microarray. Also, as a result of the efficient nature of the process, material usage is reduced by two to four orders of magnitude compared to conventional pin dispensing methods for protein spotting.

Generation of mesoscopic patterns of viable Escherichia coli by ambient laser transfer.

We have generated mesoscopic patterns of viable Escherichia coli on Si(1 1 1), glass, and nutrient agar plates by using a novel laser-based transfer process termed matrix assisted pulsed laser evaporation direct write (MAPLE DW). We observe no alterations to the E. coli induced by the laser-material interaction or the shear forces during the transfer. Transferred E. coli patterns were observed by optical and electron microscopes, and cell viability was shown through green fluorescent protein (GFP) expression and cell culturing experiments. The transfer mechanism for our approach appears remarkably gentle and suggests that active biomaterials such as proteins, DNA and antibodies could be serially deposited adjacent to viable cells. Furthermore, this technique is a direct write technology and therefore does not involve the use of masks, etching, or other lithographic tools.