Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database.

The use of myocardial perfusion (82)Rb PET/CT studies continues to increase but its accuracy using database quantification methods for the diagnosis of coronary artery disease (CAD) has not been established. METHODS: A sex-independent normal database and criteria for abnormality for rest-stress (82)Rb PET/CT myocardial perfusion imaging were developed and validated by evaluation of 281 patients (136 females: mean age +/- SD, 63.3 +/- 13.3 y; 145 males: mean age +/- SD, 63.9 +/- 12.8 y) who underwent a rest-adenosine stress (82)Rb PET/CT study. These patients were divided into 3 groups: (a) healthy group: 30 patients, with <5% likelihood of CAD (low likelihood [LLK]) based on sequential Bayesian analysis; these patients were used to generate the normal distribution; (b) pilot group: 174 patients; these patients were used to determine the optimal criteria for detecting and localizing the perfusion abnormality; and (c) validation group: 76 patients (23 with LLK of CAD and 53 who underwent coronary angiography; these patients were used for prospective validation. RESULTS: Of the 53 patients who underwent coronary angiography, 8 had <50% stenosis and 45 patients had at least one stenosis > or =50% in one major artery. Fifteen patients had single-vessel disease, 17 had double-vessel disease, and 13 had triple-vessel disease. The prospective validation shows a normalcy rate of 78% (18/23) for global CAD. The analyses by individual arteries show a normalcy rate of 96% (22/23) for the left anterior descending coronary artery, 96% for the left circumflex coronary artery (22/23), and 100% for the right coronary artery (23/23). The overall sensitivity for detection of CAD (> or =50% stenosis) was 93% (42/45). The overall specificity for detection of the absence of CAD (< or =50% stenosis) was 75% (6/8). Also, the positive predictive value for global CAD was 95% (42/44), the negative predictive value was 67% (6/9), and the accuracy was 91% (48/53). CONCLUSION: The quantitative (82)Rb PET/CT database created and validated in this study is highly accurate for the detection and localization of CAD. Physicians should consider using the quantitative output of these algorithms as decision support tools to aid with image interpretation.     

Development of the NADPH-diaphorase-positive neurons in the sympathetic ganglia

Changes in the distribution of NADPH-diaphorase (NADPH-d) were studied in neurons of the superior cervical ganglion (SCG), stellate ganglion (SG) and celiac ganglia (CG) in newborn, 10-, 20-day-old, 1-month-old, 2-month-old and 6-month-old rats, mice and kittens. NADPH-d-positive neurons were revealed in all sympathetic ganglia in kittens but not in rodents from birth onwards. In kittens, the largest population of NADPH-d-positive cells was found in the SG, the smallest in the SCG (<1%) and we observed only a few cells in the CG. The proportion of NADPH-d-positive cells in the SG increased from 3.1±0.15% in newborn kittens to 9.3±0.63% in 20-day-old animals and decreased further from 8.1±0.75% in 30-day-old kittens to 3.4±0.54% in 2-month-old animals. The content of NADPH-d-positive cells in the CG and SCG did not change during development. There were no differences in cross-sectional area between neurons located in different ganglia of animals from the same age group under study. We conclude that the development of NADPH-d-positive neurons in different sympathetic ganglia has its own time dynamics and is completed by the end of the second month of life.     

Dendritic polyglycerol nanoparticles show charge dependent bio-distribution in early human placental explants and reduce hCG secretion

A thorough understanding of nanoparticle bio-distribution at the feto-maternal interface will be a prerequisite for their diagnostic or therapeutic application in women of childbearing age and for teratologic risk assessment. Therefore, the tissue interaction of biocompatible dendritic polyglycerol nanoparticles (dPG-NPs) with first- trimester human placental explants were analyzed and compared to less sophisticated trophoblast-cell based models. First-trimester human placental explants, BeWo cells and primary trophoblast cells from human term placenta were exposed to fluorescence labeled, ～5?nm dPG-NPs, with differently charged surfaces, at concentrations of 1 µM and 10?nM, for 6 and 24?h. Accumulation of dPGs was visualized by fluorescence microscopy. To assess the impact of dPG-NP on trophoblast integrity and endocrine function, LDH, and hCG releases were measured. A dose- and charge-dependent accumulation of dPG-NPs was observed at the early placental barrier and in cell lines, with positive dPG-NP-surface causing deposits even in the mesenchymal core of the placental villi. No signs of plasma membrane damage could be detected. After 24?h we observed a significant reduction of hCG secretion in placental explants, without significant changes in trophoblast apoptosis, at low concentrations of charged dPG-NPs. In conclusion, dPG-NP’s surface charge substantially influences their bio-distribution at the feto-maternal interface, with positive charge facilitating trans-trophoblast passage, and in contrast to more artificial models, the first-trimester placental explant culture model reveals potentially hazardous influences of charged dPG-NPs on early placental physiology.     

Age-related differences in proprioceptive and visuo-proprioceptive function in relation to fine motor behaviour

Leversen et al. (PLoS One 7(6):e38830, 2012) emphasise the importance of understanding the principles of life-long development. In their study of motor control, they found a common tendency towards improved motor performance from childhood to adulthood and a subsequent deterioration. The aim of our study was to examine this issue further by investigating fine motor behaviour (tracing a model line) in 196 participants (age range 12–95 years old) in two sensory conditions—proprioceptive + visual (PV) and proprioceptive only—in both hands and in two types of movement, frontal and transversal. Regression analyses of line length and task performance speed in relation to age were conducted for the different test conditions. The best performance was found in middle age, and a quadratic function provided the best fit for most of the test conditions. The corresponding inflection points (the age at which graphical analysis showed a change in performance as a peak of maturation before decline due to ageing) showed earlier ages in the proprioceptive condition. For most types of movement analysed, performance speed was slower under the PV condition. Paired correlation analysis showed that the symmetry of precision performance between hands became stronger with age. The results provide information on age-dependent differences in proprioception based on fine motor performance. They may be of use in the design of preventive strategies for preserving proprioceptive function by reducing the risk of falls and accidents or diseases such as Parkinson’s.     

Study of the Hydrolytic Stability of Fine-Grained Ceramics Based on Y2.5Nd0.5Al5O12 Oxide with a Garnet Structure under Hydrothermal Conditions

The hydrolytic stability of ceramics based on Y_2.5Nd_0.5Al₅O₁₂ oxide with a garnet structure obtained by the spark plasma sintering (SPS) method has been studied. The tests were carried out in distilled water under hydrothermal conditions in an autoclave and, for comparison, in a static mode at room temperature. The mechanism of leaching of Y and Nd from the ceramics was investigated. It has been shown that at “low” temperatures (25 and 100 °C), the destruction of pores occured, and the intensity of the leaching process was limited by the diffusion of ions from the inner part of the sample to the surface. At “high” test temperatures (200 and 300 °C), intense destruction of the ceramic grain boundaries was observed. It was assumed that the accelerated leaching of neodymium is due to the formation of grain-boundary segregations of Nd³⁺ in sintered ceramics.     

Carbon disulphide tetratogenicity and postnatal effects in rat

Pregnant albino rats were exposed to carbon disulphide vapour in concentrations of 50, 100 or 200 $\text{mg}\text{m}{}^3$throughout gestation. Two successive generations (F₁ and F₂) were studied.Concentration levels of 100 and 200 $\text{mg}\text{m}{}^3$ produced marked dose-related impairment in the prenatal development of the F₁ progeny, with increase of early embryonal lethality, reduction in foetal weight and a high incidence of malformations affecting mostly the brain and limbs. Postnatal viability, body weight, lipid and energy metabolism and behaviour were also impaired. Behavioral deviations were observed even at 50 $\text{mg}\text{m}{}^3$.After reaching sexual maturity the F₁ rats were mated within their experimental groups, but no further carbon disulphide exposure was applied. The adverse effects on progeny were still detectable in the F₂ generation. Structural abnormalities of the same type as those found in the F₁ at 100 and 200 $\text{mg}\text{m}{}^3$ exposure were observed in their progeny and, postnatally, statistically significant behavioral changes were observed in the progeny of all test groups.     

Trends of anticardiolipin antibodies after low-dose methylprednisolone and cyclophosphamide treatment of systemic lupus erythematosus

BACKGROUND: The aim of the study is to analyze retrospectively the effect of low-dose methylprednisolone (MP) and cyclophosphamide (CYC) pulse therapy on anticardiolipin antibodies (aCL) serum levels in patients with systemic lupus erythematosus (SLE). METHODS: For aCL determinations, a beta2-glycoprotein I-dependent enzyme-linked immunosorbent test (ELISA) was performed. Lupus anticoagulant was investigated by Russell venom time with platelet neutralization. Antinuclear antibodies were performed by standardized methods. All SLE patients (from a total of 137) with aCL determinations who were assayed before and after MP and CYC pulse therapy were included in the study. RESULTS: Nine patients had aCL determinations before and after MP-CYC pulse therapy. All active patients with SLE improved clinically without severe MP-CYC side effects; 21 had IgG-aCL determinations, and 19 IgM-aCL determinations (40 assays) were performed in all nine patients during the observation period (zero time to 21 months). Three patients had secondary antiphospholipid syndrome (APLS)-related clinical manifestations. In all patients, IgG aCL antibodies decreased significantly (p <0.05). CONCLUSIONS: Decrease of IgG aCL serum levels as a consequence of the MP-CYC therapy herein reported might help to redefine previous concepts with regard to modulation of antiphospholipid antibody (aPL) immune response by immunosuppressive therapy. These findings might also have prognostic and therapeutic implications in SLE, on pregnancy in SLE, and in antiphospholipid syndrome (APL) as well, although prospective studies are required.