Plos One
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Focused ultrasound (FUS) exposure with the presence of microbubbles has been shown to transiently open the blood-brain barrier (BBB), and thus has potential to enhance the delivery of various kinds of therapeutic agents into brain tumors. The purpose of this study was to assess the preclinical therapeutic efficacy of FUS-BBB opening for enhanced temozolomide (TMZ) delivery in glioma treatment. FUS exposure with microbubbles was delivered to open the BBB of nude mice that were either normal or implanted with U87 human glioma cells. ⋯ TMZ degradation time in the tumor core was found to increase from 1.02 to 1.56 hours. Improved tumor progression and animal survival were found at different TMZ doses (up to 15% and 30%, respectively). In conclusion, this study provides preclinical evidence that FUS-BBB opening increases the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting the potential for clinical application to improve current brain tumor treatment.
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In clinical practice, there is a lack of markers for the non-invasive diagnosis and follow-up of kidney disease. Exosomes are membrane vesicles, which are secreted from their cells of origin into surrounding body fluids and contain proteins and mRNA which are protected from digestive enzymes by a cell membrane. ⋯ In this proof-of-concept study, we could demonstrate that changes in urinary exosomal cystatin C mRNA expression are representative of changes in renal mRNA and protein expression. Because cells lining the urinary tract produce urinary exosomal cystatin C mRNA, it might be a more specific marker of renal damage than glomerular-filtered free cystatin C.
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Multimorbidity is a major challenge for healthcare systems. However, currently, its magnitude and impact in healthcare expenditures is still mostly unknown. ⋯ Multimorbidity is very common for the Basque population and its prevalence rises in age, and unfavourable socioeconomic environment. The costs of care for chronic patients with several conditions cannot be described as the sum of their individual pathologies in average. They usually increase dramatically according to the number of comorbidities. Given the ageing population, multimorbidity and its consequences should be taken into account in healthcare policy, the organization of care and medical research.
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Migraineurs have atypical pain processing, increased expectations for pain, and hypervigilance for pain. Recent studies identified correlations between brain structure and pain sensation in healthy adults. The objective of this study was to compare cortical thickness-to-pain threshold correlations in migraineurs to healthy controls. We hypothesized that migraineurs would have aberrant relationships between the anatomical neurocorrelates of pain processing and pain thresholds. ⋯ Unlike healthy control subjects who have a significant negative correlation between cortical thickness in a superior temporal/inferior parietal region with pain thresholds, migraineurs have a non-significant positive correlation between cortical thickness in a superior temporal/inferior parietal region with pain thresholds. Since this region participates in orienting and attention to painful stimuli, absence of the normal correlation might represent a migraineurs inability to inhibit pain sensation via shifting attention away from the painful stimulus.
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Neuronal loss is a common component of a variety of neurodegenerative disorders (including Alzheimer's, Parkinson's, and Huntington's disease) and brain traumas (stroke, epilepsy, and traumatic brain injury). One brain region that commonly exhibits neuronal loss in several neurodegenerative disorders is the hippocampus, an area of the brain critical for the formation and retrieval of memories. Long-lasting and sometimes unrecoverable deficits caused by neuronal loss present a unique challenge for clinicians and for researchers who attempt to model these traumas in animals. ⋯ We found that we are able to inflict a consistent and significant lesion to the hippocampus, resulting in hippocampally-dependent behavioral deficits and a long-lasting upregulation in neurogenesis, suggesting that this process might be a critical part of hippocampal recovery. In addition, we provide novel evidence of angiogenic and vasculature changes following hippocampal neuronal loss in CaM/Tet-DTA mice. We posit that angiogenesis may be an important factor that promotes neurogenic upregulation following hippocampal neuronal loss, and both factors, angiogenesis and neurogenesis, can contribute to the adaptive response of the brain for behavioral recovery.