[Show abstract][Hide abstract] ABSTRACT: Abstract There are several published reports on the prevalence of low vitamin D levels in otherwise healthy Indian population. Vitamin D deficiency has shown variable effect on muscle performance and strength but there is paucity of data on the effect of vitamin D deficiency on muscle energy metabolism. The present study was proposed to investigate the influence of severe vitamin D deficiency on high-energy metabolite levels in resting skeletal muscle and thereafter, monitor the response after vitamin D supplementation using (31)P magnetic resonance spectroscopy (MRS). Study was conducted on 19 otherwise healthy subjects but with low serum 25(OH)D levels (<5 ng/ml). Subjects were supplemented with cholecalciferol at a dose of 60 000 IU/week for 12 weeks. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiester (PDE) and ATP of the calf muscle were taken pre- and post-vitamin D supplementation. The study revealed significantly increased PCr/Pi ratio and decreased [Pi] and PDE/ATP ratio with raised serum 25(OH)D levels after 12 weeks of supplementation. The study indicates that serum 25(OH)D level plays an important role in improving the skeletal muscle energy metabolism and vitamin D deficiency might be one of the primary reasons for prevalence of low PCr/Pi ratio and high PDE values in normal Indian population as reported earlier. The findings of this preliminary study are highly encouraging and warrant further in-depth research, involving larger number of subjects of different age groups, regions and socio-economic sections of the society to further strengthen a correlation between vitamin D levels and muscle energy metabolism.
No preview · Article · Mar 2014 · Endocrine Research
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Abstract Purpose: In the classical description of acute radiation syndrome, the role of central nervous system (CNS) is underestimated. It is now well recognised that ionising radiation-induced oxidative stress may bring about functional changes in the brain. In this study, we prospectively evaluated metabolic changes in the brain after whole body irradiation in mice using in vivo proton ((1)H) nuclear magnetic resonance spectroscopy (MRS).
Material and methods:
Young adult mice were exposed to whole body irradiation of 8 Gy and controls were sham irradiated. In vivo (1)H MRS from cortex-hippocampus and hypothalamic-thalamic region of brain at different time points, i.e., as early as 6 hours, day 1, 2, 3, 5 and 10 post irradiation was carried out at 7 Tesla animal magnetic resonance imaging system. Brain metabolites were measured and quantitative analysis of detectable metabolites was performed by linear combination of model (LCModel).
Significant reduction in myoinositol (p = 0.03) and taurine (p = 0.02) ratios were observed in cortex-hippocampus region as early as day 2 post irradiation compared to controls. These metabolic alterations remained sustained over day 10 post irradiation.
The results of this preliminary study suggest that the alteration/reduction in the mI and Tau concentration may be associated with physiological perturbations in astrocytes or radiation induced neuro-inflammatory response triggered in microglial cell.
Full-text · Article · Oct 2013 · International Journal of Radiation Biology
[Show abstract][Hide abstract] ABSTRACT: The field of metabolomics continues to grow rapidly over the last decade and has proven to be a powerful technique in predicting and explaining complex phenotypes in various biological systems. As one of the ‘omic’ technology, metabolomics has exciting applications in varied fields including medical science, synthetic biology, medicine and predictive modelling of plant, animal and microbial systems. Integrated application with genomics, transcriptomics and proteomics provide greater understanding of global system biology. Metabolomics is often considered a powerful tool to provide an instantaneous snapshot of the physiology of a cell. It is increasingly being used to characterize the interaction of organism with their environment. Although thermal conditions influence the development of living organism in a wide variety of ways, this topic has been recently ignored in humans. This review reintroduces thermal conditions as a topic of importance by presenting an example of how thermal conditions influence various metabolic pathways. The first section highlights the advances in metabolomics technologies followed by the effects and recent studies of organism function and metabolic responses to thermal stress, including investigations of heat and cold stress are reviewed. This review forms the basis for future studies to detect early biomarkers for thermal stress in humans and identifying population at risk. Furthermore, it can be used to develop methods to provide protection to the body against environmental insult, thereby, reducing the adverse response to thermal stress.
[Show abstract][Hide abstract] ABSTRACT: Trait anxiety, a personality dimension that measures an individual's higher disposition to anxiety, has been found to be associated with many functional consequences viz. increased distractibility, attentional bias in favor of threat-related information etc. Similarly, volumetric studies have reported morphological changes viz. a decrease in the volume of left uncinate fasciculus (fiber connecting anterior temporal areas including the amygdala with prefrontal-/orbitofrontal cortices) and an increase in the volume of the left amygdala and right hippocampus, to be associated with trait anxiety. The functional and morphological changes associated with trait anxiety might also be associated with the changes in the integrity of WM tracts in relation with the trait anxiety levels of the subjects. Therefore, in the present diffusion tensor tractography (DTT) study, we investigated the possible relationship between the diffusion tensor imaging (DTI) derived indices of a wide array of fiber tracts and the trait anxiety scores in our subject group. A positive correlation between trait anxiety scores and the mean fractional anisotropy (FA) value was obtained in fornix and left uncinate fasciculus. The study provides first account of a positive relation between sub-clinical anxiety levels of subjects and the FA of fornix thereby providing interesting insights into the biological foundation of sub-clinical anxiety.
No preview · Article · Oct 2012 · Behavioural brain research
[Show abstract][Hide abstract] ABSTRACT: The nuclear arsenal and the use of nuclear technologies have enhanced the likelihood of whole-body/partial-body radiation exposure. The central nervous system is highly susceptible to even low doses of radiation. With the aim of detecting and monitoring the pathologic changes of radiation-induced damage in brain parenchyma, we used serial diffusion tensor magnetic resonance imaging (DTI) with a 7T magnetic resonance unit and neurobehavioral assessments mice irradiated with 3-, 5-, and 8-Gy doses of radiation. Fractional anisotropy (FA) and mean diffusivity (MD) values at each time point (baseline, day 1, day 5, and day 10) were quantified from hippocampus, thalamus, hypothalamus, cudate-putamen, frontal cortex, sensorimotor cortex, corpus callosum, cingulum, and cerebral peduncle. Behavioral tests were performed at baseline, day 5, and day 10. A decrease in FA values with time was observed in all three groups. At day 10, dose-dependent decreases in FA and MD values were observed in all of the regions compared with baseline. Behavioral data obtained in this study correlate with FA values. Radiation-induced affective disorders were not radiation dose dependent, insofar as the anxiety-like symptoms at the lower dose (3 Gy) mimics to the symptoms with the higher dose (8 Gy) level but not with the moderate dose. However, there was a dose-dependent decline in cognitive function as well as FA values. Behavioral data support the DTI indices, so it is suggested that DTI may be a useful tool for noninvasive monitoring of radiation-induced brain injury.
Full-text · Article · Oct 2012 · Journal of Neuroscience Research
[Show abstract][Hide abstract] ABSTRACT: Radiation accidents are rare events that induce radiation syndrome, a complex pathology which is difficult to treat. In medical
management of radiation victims, life threatening damage to different physiological systems should be taken into consideration.
The present study was proposed to identify metabolic and physiological perturbations in biofluids of mice during different
phases of radiation sickness using 1H nuclear magnetic resonance (1H NMR) spectroscopy and pattern recognition (PR) technique. The 1H NMR spectra of the biofluids collected from mice irradiated with 5 Gray (Gy) at different time points during radiation sickness
were analysed visually and by principal components analysis. Urine and serum spectral profile clearly showed altered metabolic
profiles during different phases of radiation sickness. Increased concentration of urine metabolites viz. citrate, α ketoglutarate,
succinate, hippurate, and trimethylamine during prodromal and clinical manifestation phase of radiation sickness shows altered
gut microflora and energy metabolism. On the other hand, serum nuclear magnetic resonance (NMR) spectra reflected changes
associated with lipid, energy and membrane metabolism during radiation sickness. The metabonomic time trajectory based on
PR analysis of 1H NMR spectra of urine illustrates clear separation of irradiated mice group at different time points from pre dose. The difference
in NMR spectral profiles depicts the pathophysiological changes and metabolic disturbances observed during different phases
of radiation sickness, that in turn, demonstrate involvement of multiple organ dysfunction. This could further be useful in
development of multiparametric approach for better evaluation of radiation damage as well as for medical management during
1H NMR spectroscopy–Serum–Urine–Metabonomics
[Show abstract][Hide abstract] ABSTRACT: To investigate structural reorganization in the brain with differential visual experience using Voxel-Based Morphometry with Diffeomorphic Anatomic Registration Through Exponentiated Lie algebra algorithm (DARTEL) approach.
High resolution structural MR images were taken in fifteen normal sighted healthy controls, thirteen totally blind subjects and six partial blind subjects. The analysis was carried out using SPM8 software on MATLAB 7.6.0 platform.
VBM study revealed gray matter volume atrophy in the cerebellum and left inferior parietal cortex in total blind subjects and in left inferior parietal cortex, right caudate nucleus, and left primary visual cortex in partial blind subjects as compared to controls. White matter volume loss was found in calcarine gyrus in total blind subjects and Thlamus-somatosensory region in partially blind subjects as compared to controls. Besides, an increase in Gray Matter volume was also found in left middle occipital and middle frontal gyrus and right entorhinal cortex, and an increase in White Matter volume was found in superior frontal gyrus, left middle temporal gyrus and right Heschl's gyrus in totally blind subjects as compared to controls. Comparison between total and partial blind subjects revealed a greater Gray Matter volume in left cerebellum of partial blinds and left Brodmann area 18 of total blind subjects.
Results suggest that, loss of vision at an early age can induce significant structural reorganization on account of the loss of visual input. These plastic changes are different in early onset of total blindness as compared to partial blindness.
Full-text · Article · Nov 2011 · European journal of radiology
[Show abstract][Hide abstract] ABSTRACT: The metabolomic approach has been widely used in toxicology to investigate mechanisms of toxicity. To understand the mammalian system’s response to nickel exposure, we analysed the NiCl2 induced metabolomic changes in urine of rats using 1H nuclear magnetic resonance (1H NMR) spectroscopy together with clinically relevant biochemical parameters. Male Sprague–Dawley rats were administered intraperitoneally with NiCl2 at doses of 4, 10 and 20 mg/kg body weight. Urine samples were collected at 8, 16, 24, 72, 96 and 120 h post treatment. The metabolomic profile of rat urine showed prominent changes in citrate, dimethylamine, creatinine, choline, trimethylamine oxide (TMAO), phenyl alanine and hippurate at all doses. Principal component analysis of urine 1H NMR spectra demonstrated the dose and time dependent development of toxicity. The metabolomic time trajectory, based on pattern recognition analysis of 1H NMR spectra of urine, illustrated clear separation of pre and post treatments (temporal). Only animals treated with a low dose of NiCl2 returned to normal physiology. The 1H NMR spectral data correlated well with the clinically relevant nephrotoxic biomarkers. The urinary metabolomic phenotyping for NiCl2 induced nephrotoxicity was defined according to the predictive ability of the known metabolite biomarkers, creatinine, citrate and TMAO. The current approach demonstrates that metabolomics, one of the most important platform in system biology, may be a promising tool for identifying and characterizing biochemical responses to toxicity.
[Show abstract][Hide abstract] ABSTRACT: Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and β-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity.
No preview · Article · Oct 2011 · Journal of Applied Toxicology
[Show abstract][Hide abstract] ABSTRACT: The study was aimed to test the feasibility of utilizing an algorithmically determinable stable fiber mass (SFM) map obtained by an unsupervised principal eigenvector field segmentation (PEVFS) for automatic delineation of 18 white matter (WM) tracts: (1) corpus callosum (CC), (2) tapetum (TP), (3) inferior longitudinal fasciculus (ILF), (4) uncinate fasciculus (UNC), (5) inferior fronto-occipital fasciculus (IFO), (6) optic pathways (OP), (7) superior longitudinal fasciculus (SLF), (8) arcuate fasciculus (AF), (9) fornix (FX), (10) cingulum (CG), (11) anterior thalamic radiation (ATR), (12) superior thalamic radiation (STR), (13) posterior thalamic radiation (PTR), (14) corticospinal/corticopontine tract (CST/CPT), (15) medial lemniscus (ML), (16) superior cerebellar peduncle (SCP), (17) middle cerebellar peduncle (MCP) and (18) inferior cerebellar peduncle (ICP). Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) and the principal eigenvector field have been used to create the SFM consisting of a collection of linear voxel structures which are grouped together by color-coding them into seven natural classes to provide PEVFS signature segments which greatly facilitate the selection of regions of interest (ROIs) for fiber tractography using just a single mouse click, as compared with a manual drawing of ROIs in the classical approach. All the 18 fiber bundles have been successfully reconstructed, in all the subjects, using the single ROIs provided by the SFM approach, with their reproducibility characterized by the fact that the ROI selection is user independent. The essentially automatic PEVFS method is robust, efficient and compares favorably with the classical ROI methods for diffusion tensor tractography (DTT).
No preview · Article · Jun 2011 · Magnetic Resonance Imaging
[Show abstract][Hide abstract] ABSTRACT: Acute cold stress may trigger systemic biochemical and physiological changes in the living organisms, which leads to rapid loss of homeostasis. These changes may reverse due to self-regulatory mechanism of the organism or by the intervention of suitable medication in the form of herbs. The present study was undertaken to assess the alterations in metabolites levels arising due to acute cold stress and to monitor the restoration of these changes by suitable herb intervention. Male Sprague-Dawley rats were exposed to acute cold stress of −10°C for 3 h and urine samples were collected and analyzed by NMR spectroscopy in conjugation with Principal Component Analysis (PCA). The study revealed highly significant biochemical changes in urinary metabolites and also demonstrated the protective effects of Tinospora Cordifolia (Tc) extract on the stressed rats. These changes suggest the involvement of various metabolic pathways such as Tricarboxylic Acid (TCA) cycle, gut microbiota, renal function, catecholamines and muscle metabolism in the metabolic alterations induced by cold stress and the compensation required to restore homeostasis. The present study forms the basis of future studies to establish potential biomarkers for cold stress in humans and lay down the optimum dosage of Tc to be administered for providing immunity to the body as prophylactic and mitigating agent against environmental insult such as cold stress.
[Show abstract][Hide abstract] ABSTRACT: Acute heat stress may trigger systemic biochemical and physiological changes in living organisms leading to rapid loss of homeostasis. Metabolic regulatory process during heat stress has been poorly understood therefore the present study was undertaken in order to have an insight of alterations in various metabolites due to acute heat stress exposure using nuclear magnetic resonance (NMR) spectroscopy. Male sprague-dawley (SD) rats were exposed to acute heat stress of 45±2°C for 3 h and urine samples were collected from control (n=6) and heat stress group (n=6) on day 0 and 1. Metabolites excreted in urine were analyzed using NMR spectroscopy in conjugation with principal component analysis (PCA). The biochemical response to acute heat stress was characterized by decreased levels of citrate, succinate, 2-oxoglutrate, phenylalanine, creatinine, hippurate and elevation in formate levels. Hence, some biological pathways such as tricarboxylic acid (TCA) cycle, catecholamine activity and gut microbiota were transiently affected due to heat stress exposure. NMR based metabonomic studies in conjugation with statistical analysis permits non-invasive and simultaneous monitoring of entire metabolic pathways. This reveals the subtle interplay of functional metabolites and pathways leading to an understanding of the systemic response to external stimuli such as heat stress. These studies form the basis for future studies to detect early biomarkers for heat stress in humans and identifying the population at risk. Furthermore, it can be used to develop methods to provide protection to the body against environmental insult, thereby reducing the adverse response to heat stress.
[Show abstract][Hide abstract] ABSTRACT: Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients.
In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction.
Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery.
We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients.
31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.
No preview · Article · Apr 2011 · Journal of endocrinological investigation
[Show abstract][Hide abstract] ABSTRACT: SSPE is a persistent infection of the central nervous system caused by the measles virus. The correlation between the clinical staging and conventional MR imaging is usually poor. The purpose of this study was to determine whether tract-specific DTI measures in the major white mater tracts correlate with clinical grades as defined by the Jabbour classification for SSPE.
Quantitative DTT was performed on 20 patients with SSPE (mean age, 9 years) and 14 age- and sex-matched controls. All patients were graded on the basis of the Jabbour classification into grade II (n=9), grade III (n=6), and grade IV (n=5) SSPE. The major white matter tracts quantified included the CC, SLF, ILF, CST, CNG, SCP, MCP, ICP, ATR, STR, and PTR.
Although a successive decrease in mean FA values was observed in all the fiber tracts except for the SCP and ICP, moving from controls to grade IV, a significant inverse correlation between clinical grade and mean FA values was observed only in the splenium (r=-0.908, P<.001), CST (r=-0.663, P=.013), SLF (r=-0.533, P=.050), ILF (r=-0.776, P=.001), STR (r=-0.538, P=.047), and PTR (r=-0.686, P=.035) fibers. No significant correlation of mean MD values from these white matter tracts was observed with clinical grades of the disease.
We conclude that the grade of encephalopathy correlates inversely with the tract-specific mean FA values. This information may be valuable in studying the disease progression with time and in assessing the therapeutic response in the future.
Full-text · Article · Feb 2011 · American Journal of Neuroradiology
[Show abstract][Hide abstract] ABSTRACT: Radiation exposure induces change in many biological compounds. It is important to assess the physiological and biochemical response to an absorbed dose of ionising radiation due to intentional or accidental event and to predict medical consequences for medical management. In the present study, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used in mice serum for identification of radiation-induced changes at metabolite level.
Mice were irradiated with 3, 5 and 8 Gray of γ-radiation dose and serum samples collected at day 1, 3 and 5 post irradiation were analysed by proton nuclear magnetic resonance (¹H NMR) spectroscopy. ¹H NMR spectra of serum were analysed by pattern recognition using principal component analysis.
Irradiated mice serum showed distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of irradiated groups. ¹H NMR spectral analysis exhibited increased lactate, amino acids, choline and lipid signals as well as decreased glucose signals. These findings indicate radiation-induced disturbed energy, lipid and protein metabolism.
The information obtained from this study reflects multiple physiological dysfunctions. The study promises the application of NMR-based metabonomics in the field of radiobiology, for development of metabolic-based markers for screening of risk populations and medical management in these cases.
No preview · Article · Nov 2010 · International Journal of Radiation Biology
[Show abstract][Hide abstract] ABSTRACT: Mitochondrial metabolism particularly oxidative phosphorylation is greatly influenced by thyroid hormones. Earlier studies have described neuromuscular symptoms as well as impaired muscle metabolism in hypothyroid and hyperthyroid patients. In this study, we intend to look in to the muscle bioenergetics including phosphocreatine recovery kinetics based oxidative metabolism in thyroid dysfunction using in vivo (31)P nuclear magnetic resonance spectroscopy (MRS). (31)P MRS was carried out at resting state on 32 hypothyroid, 10 hyperthyroid patients and 25 control subjects. Nine out of 32 hypothyroid patients and 17 out of 25 control subjects under went exercise protocol for oxidative metabolism study and performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiesters (PDE) and adenosine triphosphate (ATP) of the calf muscle were acquired during rest, exercise and recovery phase. PCr recovery rate constant (k(PCr)) and oxidative capacity were calculated by monoexponential fit of PCr versus time (t) at the beginning of recovery. During resting condition in hypothyroid patients, PCr/Pi ratio was reduced whereas PDE/ATP and Pi/ATP were increased. However, in case of hyperthyroidism, an increased PCr/Pi ratio and reduced PDE/ATP and Pi/ATP were observed. The results confirmed differential energy status of the muscle due to increased or decreased levels of thyroid hormone. Our results also demonstrate reduced oxidative metabolism in hypothyroid patients based on PCr recovery kinetics. PCr recovery kinetics study after exercise revealed decreased PCr recovery rate constant (k(PCr)) in hypothyroid patients compared to controls that resulted in decrease in oxidative capacity of muscle by 50% in hypothyroids. These findings are consistent with a defect of high energy phosphate mitochondrial metabolism in thyroid dysfunction.
No preview · Article · Mar 2010 · Magnetic Resonance Imaging
[Show abstract][Hide abstract] ABSTRACT: Chronic alcoholism is associated with altered brain metabolism, morphology and cognitive abilities. Besides deficits in higher order cognitive functions, alcoholics also show a deficit in the processing of basic sensory information viz. visual stimulation. To assess the metabolic changes associated with this deficit, (1)H MRS was carried out in the occipital lobe of alcohol dependents. A significant increase in Cho/Cr ratio (p<0.015) was observed in occipital lobe in the alcoholic group indicating altered cell membrane metabolism, which may probably be associated with the alterations in the cognitive abilities associated with vision.
Full-text · Article · Dec 2009 · European journal of radiology