Quantitative metabolomics of saliva using proton NMR spectroscopy in patients with Parkinson's disease and healthy controls.

INTRODUCTION: Parkinson's disease (PD) is a multisystem disorder of unknown etiology, highlights a broad array of symptoms and pathological features influencing organs throughout the body. The metabolic profile of saliva in patients with PD may be influenced by malabsorption in the gastroenteric tract, neurodegeneration, and mitochondrial dysfunction. In the present study, we apply a powerful NMR metabolomics approach for biomarker identification in PD using saliva, a non-invasive bio-fluid. METHODS: Metabolic profiling of saliva were studied in patients with PD (n = 76) and healthy controls (HC, n = 37) were analyzed and differentiated PD from HC. A total of 40 metabolites including aromatic amino acids, short-chain fatty acids, branched chain amino acids, taurine, and N-acetylglutamate were identified. Spectral binned data and concentration of metabolites were estimated for analysis. RESULTS: Increased concentration of phenylalanine, tyrosine, histidine, glycine, acetoacetate, taurine, TMAO, GABA, N-acetylglutamate, acetoin, acetate, alanine, fucose, propionate, isoleucine, and valine were observed in PD as compared to HC. Further, subgroup analysis among early PD, advanced PD, and HC groups, revealed increased metabolite concentration in early PD group as compared to advanced PD and HC group. DISCUSSION: Analysis revealed potential biomarkers and their involvement in amino acid metabolism, energy metabolism, neurotransmitters metabolism, and microflora system. Patients with early PD exhibited higher metabolite concentration as compared to advanced PD group which might be associated with dopaminergic treatment. CONCLUSION: The results of our data indicate that patients with PD might be characterized by metabolic imbalances like gut microflora system, energy metabolites, and neurotransmitters which may contribute to the PD pathogenesis.

Gray Matter Atrophy in a 6-OHDA-induced Model of Parkinson's Disease.

INTRODUCTION: Magnetic resonance imaging (MRI) based brain morphometric changes in unilateral 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model can be elucidated using voxel-based morphometry (VBM), study of alterations in gray matter volume and Machine Learning (ML) based analyses. METHODS: We investigated gray matter atrophy in 6-OHDA induced PD model as compared to sham control using statistical and ML based analysis. VBM and atlas-based volumetric analysis was carried out at regional level. Support vector machine (SVM)-based algorithms wherein features (volume) extracted from (a) each of the 150 brain regions (b) statistically significant features (only) and (c) volumes of each cluster identified after application of VBM (VBM_Vol) were used for training the decision model. The lesion of the 6-OHDA model was validated by estimating the net contralateral rotational behaviour by the injection of apomorphine drug and motor impairment was assessed by rotarod and open field test. RESULTS AND DISCUSSION: In PD, gray matter volume (GMV) atrophy was noted in bilateral cortical and subcortical brain regions, especially in the internal capsule, substantia nigra, midbrain, primary motor cortex and basal ganglia-thalamocortical circuits in comparison with sham control. Behavioural results revealed an impairment in motor performance. SVM analysis showed 100% classification accuracy, sensitivity and specificity at both 3 and 7 weeks using VBM_Vol. CONCLUSION: Unilateral 6-OHDA induced GMV changes in both hemispheres at 7th week may be associated with progression of the disease in the PD model. SVM based approaches provide an increased classification accuracy to elucidate GMV atrophy.

Imaging application and radiosensitivity enhancement of pectin decorated multifunctional magnetic nanoparticles in cancer therapy.

In this contribution, we report the fabrication of multifunctional nanoparticles with gold shell over an iron oxide nanoparticles (INPs) core. The fabricated system combines the magnetic property of INPs and the surface plasmon resonance of gold. The developed nanoparticles are coated with thiolated pectin (TPGINs), which provides stability to the nanoparticles dispersion and allows the loading of hydrophobic anticancer drugs. Curcumin (Cur) is used as the model drug and an encapsulation efficiency of approximately 80% in TPGINs is observed. Cytotoxicity study with HeLa cells shows that Cur-loaded TPGINs have better viability percent (~30%) than Cur alone (~40%) at a dose of 30 µg of TPGINs. Further, annexin V-PI assay demonstrated the enhanced anticancer activity of Cur-loaded TPGINs via induction of apoptosis. The use of TPGINs leads to a significant enhancement in generating reactive oxygen species (ROS) in HeLa cells through improved radiosensitization by gamma irradiation (0.5 Gy). TPGINs are further evaluated for imparting contrast in magnetic resonance imaging (MRI) with the r2 relaxivity in the range of 11.06-13.94 s-1 µg-1 mL when measured at 7 Tesla. These experimental results indicate the potential of TPGINs for drug delivery and MR imaging.

Identification of potential urine biomarkers in idiopathic parkinson's disease using NMR.

INTRODUCTION: Parkinson's disease (PD) is the most common neurodegenerative disease caused by the loss of dopamine chemicals resulting in urinary incontinence, gastrointestinal dysfunction, gait impairment and mitochondrial dysfunction. Study investigated urinary metabolic profiles of patients with idiopathic PD as compared to healthy controls (HC) to identify the potential biomarkers. METHODS: Urine samples were collected from 100 PD subjects and 50 HC using standard protocol. Metabolomic analyses were performed using high resolution nuclear magnetic resonance (NMR) spectroscopy. The integral values of 17 significant metabolites were estimated and concentration values were calculated, which were subjected to univariate and multivariate statistical analysis. RESULTS: We found significantly increased levels of ornithine, phenylalanine, isoleucine, ß-hydroxybutyrate, tyrosine and succinate in the urine of patients with PD in comparison with HC. These metabolites exhibited area under the curve greater than 0.60 on ROC curve analysis. We also observed a significant association between succinate concentration and UPDRS motor scores of PD. DISCUSSION: Metabolic pathway alterations were observed in aromatic amino acid metabolism, ketone bodies synthesis, branched chain amino acid metabolism and ornithine metabolism. Comprehensive metabolomic profiling revealed variations in urinary signatures associated with severity of idiopathic PD. This profiling relies on non-invasive sampling and is complementary to existing clinical modalities.

Bilateral Sturge-Weber and Phakomatosis Pigmentovascularis with Glaucoma, an Overlap Syndrome.

UNLABELLED: Aim. To report a case of bilateral Sturge-Weber and Phakomatosis pigmentovascularis with secondary glaucoma in a child. Method. CASE REPORT: Results. A 4-year-old male child was referred to us for control of intraocular pressure (IOP). Sleeping IOP was 36 mm Hg in right eye and 28 mm Hg in the left eye. The sclera of both the eyes showed bluish black pigmentation-melanosis bulbi. Fundus examination of both eyes showed diffuse choroidal hemangiomas with glaucomatous cupping. Nevus flammeus was present on both sides of face along all the 3 divisions of trigeminal nerve with overlying hypertrophy of skin and on left forearm. Nevus fuscocaeruleus was present on upper trunk. All skin lesions were present since birth and were stationary in nature. CT scan of head revealed left-sided cerebral atrophy. Intraocular pressure was controlled after treatment with topical antiglaucoma medications. Pulsed Dye Laser has been advised by dermatologist for skin lesions. Patient has been advised for regular follow-up. Conclusion. The two overlapping dermatological disorders and their association with glaucoma are a rare entity. Management should be targeted both for dermatological and eye conditions.