Parkinson's disease‐cognitive rating scale: A new cognitive scale specific for Parkinson's disease

Cognitive defects associated with cortical pathology may be a marker of dementia in Parkinson's disease (PD). There is a need to improve the diagnostic criteria of PD dementia (PDD) and to clarify the cognitive impairment patterns associated with PD. Current neuropsychological batteries designed for PD are focused on fronto‐subcortical deficits but are not sensitive for cortical dysfunction. We developed a new scale, the Parkinson's Disease‐Cognitive Rating Scale (PD‐CRS), that was designed to cover the full spectrum of cognitive defects associated with PD. We prospectively studied 92 PD patients [30 cognitively intact (CogInt), 30 mild cognitive impairment (MCI), 32 PDD] and 61 matched controls who completed the PD‐CRS and neuropsychological tests assessing the cognitive domains included in the PD‐CRS. Acceptability, construct validity, reliability, and the discriminative properties of the PD‐CRS were examined. The PD‐CRS included items assessing fronto‐subcortical defects and items assessing cortical dysfunction. Construct validity, test‐retest and inter‐rater reliability of PD‐CRS total scores showed an intraclass correlation coefficient >0.70. The PD‐CRS showed an excellent test accuracy to diagnose PDD (sensitivity 94%, specificity 94%). The PD‐CRS total scores and confrontation naming item scores‐assessing “cortical” dysfunction—independently differentiated PDD from non‐demented PD. Alternating verbal fluency and delayed verbal memory independently differentiated the MCI group from both controls and CogInt. The PD‐CRS appeared to be a reliable and valid PD‐specific battery that accurately diagnosed PDD and detected subtle fronto‐subcortical deficits. Performance on the PD‐CRS showed that PDD is characterized by the addition of cortical dysfunction upon a predominant and progressive fronto‐subcortical impairment. © 2008 Movement Disorder Society     

Reproducibility and Angle Independence of Electromechanical Wave Imaging for the Measurement of Electromechanical Activation during Sinus Rhythm in Healthy Humans

Electromechanical wave imaging (EWI) is an ultrasound-based technique that can non-invasively map the transmural electromechanical activation in all four cardiac chambers in vivo. The objective of this study was to determine the reproducibility and angle independence of EWI for the assessment of electromechanical activation during normal sinus rhythm (NSR) in healthy humans. Acquisitions were performed transthoracically at 2000 frames/s on seven healthy human hearts in parasternal long-axis, apical four- and two-chamber views. EWI data was collected twice successively in each view in all subjects, while four successive acquisitions were obtained in one case. Activation maps were generated and compared (i) within the same acquisition across consecutive cardiac cycles; (ii) within same view across successive acquisitions; and (iii) within equivalent left-ventricular regions across different views. EWI was capable of characterizing electromechanical activation during NSR and of reliably obtaining similar patterns of activation. For consecutive heart cycles, the average 2-D correlation coefficient between the two isochrones across the seven subjects was 0.9893, with a mean average activation time fluctuation in LV wall segments across acquisitions of 6.19%. A mean activation time variability of 12% was obtained across different views with a measurement bias of only 3.2 ms. These findings indicate that EWI can map the electromechanical activation during NSR in human hearts in transthoracic echocardiography in vivo and results in reproducible and angle-independent activation maps.     

In vitro evaluation of (S)-ibuprofen toxicity on joint cells and explants of cartilage and synovial membrane

Intra-articular drug delivery systems (DDSs) are envisaged as interesting alternative to locally release nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen to reduce pain in patients with osteoarthritis. The present study examines the toxicity of (S)-ibuprofen on chondrocytes and synoviocytes isolated from sheep shoulder joint and cultured in monolayers during 72 h, and on joint explants (cartilage and capsule) cultured in mono- or in co-culture for 13 days. (S)-ibuprofen (5 μM up to 1 mM) did not reduce the cell viability and protein content when added on chondrocyte monolayers, while at 1 mM (S)-ibuprofen reduced (by 8%, p = 0.01) the synoviocytes viability compared to untreated cells. During co-culture of joint explants, (S)-ibuprofen at 50 μM significantly reduced by 35% the spontaneous release of glycosaminoglycans (GAGs) from cartilage (p = 0.0065) whereas in monoculture, (S)-ibuprofen was inactive on GAG metabolism. (S)-ibuprofen at 1 mM significantly reduced cell lysis (lactate dehydrogenase leakage) by 74% during monoculture of capsule explants (p = 0.0136) and by 35% during co-culture of explants (p = 0.0013). Our findings demonstrate that the active isomer of ibuprofen at micro- and millimolar levels was not toxic for chondrocytes and synoviocytes and may reduce at 1 mM the cell lysis during culture of joint explants. The limited toxicity of (S)-ibuprofen at low and high concentration in sheep joint shoulder makes this enantiomer a promising drug candidate for the loading of intra-articular DDS.     

Renal studies provide an insight into cardiac extracellular matrix remodeling during health and disease

The remodeling of a heart ventricle after myocardial infarction involves numerous inflammatory mediators that may trigger a long-lasting and a highly fibrogenic process. Likewise, in the kidney, acute and chronic injuries may lead to abnormal extracellular matrix deposition and eventually lead to the loss of renal function. Major breakthroughs have emerged during the last ten years with respect to the pathophysiology of matrix remodeling. Epithelial and endothelial cells are plastic, and able to engage in epithelial (or endothelial)-to-mesenchymal transition (EMT or EndMT), thus actively contributing to the fibrogenesis. Members of the fibrinolytic system were demonstrated to possess unsuspected properties and interact with receptors and integrins on endothelial and epithelial cells. Finally, a notion that stem cells could integrate into damaged tissue has recently emerged, which likely contributes to the tissue repair. In many aspects, the kidney and the heart share many common injury mechanisms. We envision that some of them will be accessible as common therapeutic targets in the future.     

Aging-related Decrease of Human ASC Angiogenic Potential Is Reversed by Hypoxia Preconditioning Through ROS Production

Adipose stroma/stem cells (ASC) represent an ideal source of autologous cells for cell-based therapy. Their transplantation enhances neovascularization after experimental ischemic injury. Aging is associated with a progressive decrease in the regenerative potential of mesenchymal stem cells (MSCs) from bone marrow. This work aims to determine the aging effect on human ASC capacities. First, we show that aging impairs angiogenic capacities of human ASC (hASC) in a mouse ischemic hindlimb model. Although no change in hASC number, phenotype, and proliferation was observed with aging, several mechanisms involved in the adverse effects of aging have been identified in vitro combining a concomitant decrease in (i) ASC ability to differentiate towards endothelial cells, (ii) secretion of proangiogenic and pro-survival factors, and (iii) oxidative stress. These effects were counteracted by a hypoxic preconditioning that improved in vivo angiogenic capacities of hASC from older donors, while hASC from young donors that have a strong ability to manage hypoxic stress were not. Finally, we identified reactive oxygen species (ROS) generation as a key signal of hypoxia on hASC angiogenic capacities. This study demonstrates for the first time that age of donor impaired angiogenic capacities of hASC in ischemic muscle and change in ROS generation by hypoxic preconditioning reverse the adverse effect of aging.     

Fast gated EPR imaging of the beating heart: Spatiotemporally resolved 3D imaging of free‐radical distribution during the cardiac cycle

In vivo or ex vivo electron paramagnetic resonance imaging (EPRI) is a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. However, applications of EPRI have been limited by long projection acquisition times and the consequent fact that rapid gated EPRI was not possible. Hence in vivo EPRI typically provided only time‐averaged information. In order to achieve direct gated EPRI, a fast EPR acquisition scheme was developed to decrease EPR projection acquisition time down to 10–20 ms, along with corresponding software and instrumentation to achieve fast gated EPRI of the isolated beating heart with submillimeter spatial resolution in as little as 2–3 min. Reconstructed images display temporal and spatial variations of the free‐radical distribution, anatomical structure, and contractile function within the rat heart during the cardiac cycle. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Maternal protein malnutrition induces autism-like symptoms in rat offspring

Objective: We tested the correlation between maternal protein malnutrition and autistic-like symptoms using behavioral tests in rodents that measure main behavioral characteristics observed in humans with autism spectrum disorder (ASD).

Methods: Pregnant female rats were fed a normal diet or a hypoproteic diet during gestation and lactation periods. The litters were weighed every 3 days during lactation, and the offspring were tested in behavioral tasks during infancy (postnatal day (PND) 5: quantification of ultrasonic vocalizations; PND 13: homing behavior test) and adolescence (PND 30–32: open field, hole-board, play social behavior, and object recognition tests) in order to capture the prevalence of some of the core and associated symptoms of ASD.

Results: Litters of the hypoproteic diet group had a lesser weight gain during lactation. In addition, pups of dams fed with a hypoproteic diet vocalized less compared to those fed with a normal diet, and they showed impaired social discrimination abilities in the homing behavior test. In adolescence, both male and female offspring of the hypoproteic diet group showed no impairment in locomotor activity; however, they exhibited stereotypic behavior in the hole-board test and a decrease in social play behaviors. Male offspring showed increased interest in exploring a familiar object rather than a novel object.

Conclusion: Our results show that maternal protein malnutrition in rats causes offspring behaviors that resemble core and associated ASD symptoms.