Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Self-reported health status and access to health services in a sample of prisoners in Italy

<p>Abstract</p> <p>Background</p> <p>Self-reported health status in underserved population of prisoners has not been extensively explored. The purposes of this cross-sectional study were to assess self-reported health, quality of life, and access to health services in a sample of male prisoners of Italy.</p> <p>Methods</p> <p>A total of 908 prisoners received a self-administered anonymous questionnaire pertaining on demographic and detention characteristics, self-reported health status and quality of life, access to health services, lifestyles, and participation to preventive, social, and rehabilitation programs. A total of 650 prisoners agreed to participate in the study and returned the questionnaire.</p> <p>Results</p> <p>Respectively, 31.6% and 43.5% of prisoners reported a poor perceived health status and a poor quality of life, and 60% admitted that their health was worsened or greatly worsened during the prison stay. Older age, lower education, psychiatric disorders, self-reported health problems on prison entry, and suicide attempts within prison were significantly associated with a perceived worse health status. At the time of the questionnaire delivery, 30% of the prisoners self-reported a health problem present on prison entry and 82% present at the time of the survey. Most frequently reported health problems included dental health problems, arthritis or joint pain, eye problems, gastrointestinal diseases, emotional problems, and high blood pressure. On average, prisoners encountered general practitioners six times during the previous year, and the frequency of medical encounters was significantly associated with older age, sentenced prisoners, psychiatric disorders, and self-reported health problems on prison entry.</p> <p>Conclusions</p> <p>The findings suggest that prisoners have a perceived poor health status, specific care needs and health promotion programs are seldom offered. Programs for correction of risk behaviour and prevention of long-term effects of incarceration on prisoners' health are strongly needed.</p

The Anti-Ischemic and Anti-Anginal Properties of Statins

Angina pectoris resulting from myocardial ischemia afflicts half of all patients with coronary heart disease (CHD). Chronic angina remains a major public health burden despite state-of-the-art therapies, and improvement in survival from myocardial infarction and CHD has only increased its prevalence. There is growing experimental and clinical evidence pointing to the anti-ischemic and anti-anginal properties of statins. Some data suggest that the degree of anti-ischemic efficacy of statins may be comparable to the current standard pharmacologic and mechanical strategies. The pleiotropic effects of statins are postulated to be primarily responsible for their anti-ischemic and anti-anginal properties. These include improvement of endothelial function, enhancement of the ischemic vasodilatory response, modulation of inflammation, and protection from ischemia-reperfusion injury. The anti-ischemic effects of statins further strengthen their role as a crucial component of the optimal medical therapy for CHD

Primary medical care in Irish prisons

BACKGROUND: An industrial dispute between prison doctors and the Irish Prison Service (IPS) took place in 2004. Part of the resolution of that dispute was that an independent review of prison medical and support services be carried out by a University Department of Primary Care. The review took place in 2008 and we report here on the principal findings of that review. METHODS: This study utilised a mixed methods approach. An independent expert medical evaluator (one of the authors, DT) inspected the medical facilities, equipment and relevant custodial areas in eleven of the fourteen prisons within the IPS. Semistructured interviews took place with personnel who had operational responsibility for delivery of prison medical care. Prison doctors completed a questionnaire to elicit issues such as allocation of clinician's time, nurse and administrative support and resources available. RESULTS: There was wide variation in the standard of medical facilities and infrastructure provided across the IPS. The range of medical equipment available was generally below that of the equivalent general practice scheme in the community. There is inequality within the system with regard to the ratio of doctor-contracted time relative to the size of the prison population. There is limited administrative support, with the majority of prisons not having a medical secretary. There are few psychiatric or counselling sessions available. CONCLUSIONS: People in prison have a wide range of medical care needs and there is evidence to suggest that these needs are being met inconsistently in Irish prisons

Olfactory Stem Cells, a New Cellular Model for Studying Molecular Mechanisms Underlying Familial Dysautonomia

International audienceBackground: Familial dysautonomia (FD) is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we collected human olfactory ecto-mesenchymal stem cells (hOE-MSC) from FD patients. hOE-MSCs have a pluripotent ability to differentiate into various cell lineages, including neurons and glial cells.Methodology/Principal Findings: We confirmed IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced isoforms also present in control cells. We observed a significant lower expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting from the degradation of the transcript isoform skipping exon 20. We localized IKAP/hELP1 in different cell compartments, including the nucleus, which supports multiple roles for that protein. We also investigated cellular pathways altered in FD, at the genome-wide level, and confirmed that cell migration and cytoskeleton reorganization were among the processes altered in FD. Indeed, FD hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20 inclusion):MU (exon 20 skipping) ratio respectively, either by producing free-floating spheres, or by inducing cells into neural differentiation.Conclusions/Significance: hOE-MSCs isolated from FD patients represent a new approach for modeling FD to better understand genetic expression and possible therapeutic approaches. This model could also be applied to other neurological genetic diseases

Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) has been noted to produce ischemic preconditioning (IPC)-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS) by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM). The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat.</p> <p>Methods</p> <p>Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, <it>i.p</it>,) and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H). Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC) staining, and release of lactate dehydrogenase (LDH) and creatin kinase-MB (CK-MB) in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent.</p> <p>Results</p> <p>IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ) a caveolin inhibitor (0.2 mg/Kg/s.c), for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 μM/L), a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD), a mito K_ATPchannel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination.</p> <p>Conclusions</p> <p>Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in the diabetic myocardium, which may be due to up -regulation of caveolin and subsequently decreased activity of eNOS.</p

Comparison of the clonogenic survival of A549 non-small cell lung adenocarcinoma cells after irradiation with low-dose-rate beta particles and high-dose-rate X-rays

Purpose: Lung cancer is the leading cause of cancer-related death. Among the new modalities to treat cancer, internal radiotherapy seems to be very promising. However, the achievable dose-rate is two orders of magnitude lower than the one used in conventional external radiotherapy, and data has to be collected to evaluate the cell response to highlight the potential effectiveness of low-dose-rate beta particles irradiation. This work investigates the phosphorus beta irradiation ( P) dose response on the clonogenicity of human A549 non-small cell lung adenocarcinoma cells and compares it to high-dose-rate X-irradiations results. Materials and methods: Cell survival was evaluated by a colony forming assay eight days after low-dose-rate P beta irradiations (0.8 Gy/h) and high-dose-rate X-ray irradiations (0.855 Gy/min). Results: Survival curves were obtained for both types of irradiations, and showed hyper-radiosensitivity at very low doses. Radiosensitivity parameters were obtained by using the linear-quadratic and induced-repair models. Conclusions: Comparison with high-dose-rate X-rays shows a similar surviving fraction, confirming the effectiveness of beta particles for tumor sterilization. © 2012 Informa UK, Ltd

Identification of a resistance gene Rpi-dlc1 to Phytophthora infestans in European accessions of Solanum dulcamara

Initial screening of 14 Solanum dulcamara accessions enabled the identification of individuals resistant and susceptible to Phytophthora infestans. Crosses between contrasting genotypes resulted in three F2–BC1 populations segregating for resistance to late blight in a laboratory assay and under field conditions. Genetic profiling of one of these populations using 128 AFLP primers generated three markers linked to the resistant phenotype. Blast analysis of the sequenced markers resulted in a plausible gene position on the distal end of the long arm of chromosome 9 that could be confirmed by CAPS markers. Thus, we describe a first resistant gene, named Rpi-dlc1, from S. dulcamara, a Solanum species native to Europe. In addition, one population was tested for broadness of resistance responses using a set of seven additional P. infestans isolates, varying in virulence. This indicated the possible presence of additional Rpi genes