Prodromal non-motor symptoms of Parkinson’s disease

The motor symptoms of Parkinson’s disease (PD), bradykinesia, muscular rigidity, and tremor depend upon degeneration of the dopaminergic neurons in the substantia nigra pars compacta. Recent neuropathological studies show that the Lewy bodies, the intraneuronal landmark of PD, accumulate in several neuronal cell types in the brain. An ascending gradient of pathological involvement, from the medulla oblongata to neocortical areas has been reported. Thus the original view of PD as a disease characterized by selective damage of the dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder. Additionally, the neuropathological alterations outside the substantia nigra are soundly correlated with the non-motor symptoms of PD. As a result of these findings, interest is growing in the identification of prodromal non-motor symptoms of PD. Indeed, data from the literature suggest that autonomic disturbances, olfactory dysfunctions, depression and sleep disorders (in particular REM-sleep behavior disorder) may represent prodromal non-motor symptoms of PD. Several tests are available to detect most of these symptoms. Thus, the identification of prodromal non-motor symptoms may contribute to the precocious diagnosis of PD, and might be useful in the future to test the efficacy of neuroprotective agents

What is a GMC? Are observers and simulators discussing the same star-forming clouds?

As both simulations and observations reach the resolution of the star-forming molecular clouds, it becomes important to clarify if these two techniques are discussing the same objects in galaxies. We compare clouds formed in a high-resolution galaxy simulation identified as continuous structures within a contour, in the simulator's position-position-position (PPP) coordinate space and the observer's position-position-velocity space (PPV). Results indicate that the properties of the cloud populations are similar in both methods and up to 70 per cent of clouds have a single counterpart in the opposite data structure. Comparing individual clouds in a one-to-one match reveals a scatter in properties mostly within a factor of 2. However, the small variations in mass, radius and velocity dispersion produce significant differences in derived quantities such as the virial parameter. This makes it difficult to determine if a structure is truly gravitationally bound. The three cloud types originally found in the simulation in Fujimoto et al. are identified in both data sets, with around 80 per cent of the clouds retaining their type between identification methods. We also compared our results when using a peak decomposition method to identify clouds in both PPP and PPV space. The number of clouds increased with this technique, but the overall cloud properties remained similar. However, the more crowded environment lowered the ability to match clouds between techniques to 40 per cent. The three cloud types also became harder to separate, especially in the PPV data set. The method used for cloud identification therefore plays a critical role in determining cloud properties, but both PPP and PPV can potentially identify the same structure

Bupropion abates dopamine agonist-mediated compulsive behaviors in Parkinson's disease.

Compulsive behaviors are relatively frequent complications of Parkinson’s disease (PD).1 Risk factors for compulsive behaviors in PD include novelty-seeking personality traits, depressive symptoms, young age, and cumulative dose of dopaminergic drugs, in particular dopamine agonists (DA). Although the pathophysiology of DA-mediated compulsive behaviors in PD is not completely defined at present, altered and pulsatile mesolimbic dopaminergic stimulation may play a fundamental rol

Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review

Network medicine is a molecular-bioinformatic approach analyzing gene-gene interactions that can perturb the human interactome. This review focuses on epigenetic changes involved in several ocular diseases, such as DNA methylation, histone and nonhistone post-translational modifications, and noncoding RNA regulators. Although changes in aberrant DNA methylation play a major role in the pathogenesis of most ocular diseases, histone modifications are seldom investigated. Hypermethylation in TGM-2 and hypomethylation in MMP-2/CD24 promoter genes may play a crucial role in pterygium development; hypermethylation in regulatory regions of GSTP1 and OGG1 genes appear to be diagnostic biomarkers of cataract; hypomethylation of TGF-β1 promoter may trigger glaucoma onset; hypermethylation of the LOXL1 gene might be associated with pseudoexfoliation syndrome. A large panel of upregulated micro-RNAs (miRNAs), including hsa-hsa-miR-494, hsa-let-7e, hsa-miR-513-1, hsa-miR-513-2, hsa-miR-518c, hsa-miR-129-1, hsa-miR-129-2, hsa-miR-198, hsa-miR-492, hsa-miR-498, hsa-miR-320, hsa-miR-503, and hsa-miR-373,∗ may have a putative role in the development of retinoblastoma. Hypermethylation of H3K4 and hypomethylation of H3K27 at the TGFBIp locus are putative pathogenic mechanisms involved in corneal dystrophies. Determining how, where, and when specific epigenetic changes trigger ocular diseases may provide useful clinical biomarkers for their prevention, diagnosis, and management, as well as innovative drug targets. PF-04523655, a 19-nucleotide methylated double-stranded siRNA targeting the RTP80 gene, showed a dose-related improvement in best-corrected visual acuity (BCVA) in patients affected by diabetic macular edema. The observed results support a clinical network-based research program aimed to clarify the role of epigenetic regulators in the development of ocular diseases and personalized therapy

Minocycline in amyotrophic lateral sclerosis: a pilot study

Recent studies indicate that minocycline exerts neuroprotective effects in vitro and in vivo, and suggest that the drug may represent a novel therapeutic approach to amyotrophic lateral sclerosis (ALS). In this study we investigated the safety of combined treatment with minocycline and riluzole in ALS. Twenty ALS patients were randomised into two groups and administered either riluzole (50 mg b.i.d.) or riluzole and minocycline (100 mg i.d.) for 6 months. Disease progression was measured by means of the ALS-Functional Rating Scale score at monthly intervals. Respiratory function was measured at the beginning of the study and repeated after 3 and 6 months of treatment. Combined treatment with minocycline and riluzole was not followed by significant side effects. This pilot study shows that minocycline and riluzole can be taken safely together. Further trials are needed to assess efficacy of such treatment

The impact of extended release dopamine agonists on prescribing patterns for therapy of early Parkinson’s disease: an observational study.

BACKGROUND: Dopamine agonists (DA) are the first-choice drug for treatment of the early stage of Parkinson's disease (PD) in subjects younger than 70 years. Recently, a number of third generation DA have been marketed, including transdermal patch of rotigotine and extended release oral formulation of ropinirole and pramipexole.We investigated the impact of third generation DA on management of the early stage of PD in an outpatient service for Movement Disorders in Italy. METHODS: Two 12-month observation periods were selected (January - December, 2007, and January - December, 2011) as representative for prescription of immediate and extended release formulations of DA respectively. Within each period, PD patients were divided into subgroups according to age (75 years) or functional requirement (high; moderate; low). For each period, the number of subjects receiving monotherapy with DA, monotherapy with levodopa (LD), or combined DA/LD therapy and the relative doses were calculated. The severity of parkinsonian motor symptoms was calculated by means of the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The frequency and severity of side-effects leading to discontinuation or reduction of DA drugs at each time point were also calculated. RESULTS: We found a significant reduction of daily LD dose (both as mono- and combined therapy) between the second and the first observation period. There was also a significant increase of monotherapy with DA and corresponding reduction of monotherapy with LD in patients aged 65-75 years, as well as in PD patients with moderate functional requirements. A significant reduction of frequency of side-effects was measured with extended release DA as compared to immediate release formulations. There were no significant differences of the UPDRS-III scores between the 2 observation periods in any subgroup. CONCLUSIONS: Our results suggest that extended release DA might optimize therapeutic management of the early stages of PD even in patients older than 70 years of age