Structural and white matter changes associated with duration of Braille education in early and late blind children.

In early (EB) and late blind (LB) children, vision deprivation produces cross-modal plasticity in the visual cortex. The progression of structural- and tract-based spatial statistics changes in the visual cortex in EB and LB, as well as their impact on global cognition, have yet to be investigated. The purpose of this study was to determine the cortical thickness (CT), gyrification index (GI), and white matter (WM) integrity in EB and LB children, as well as their association to the duration of blindness and education. Structural and diffusion tensor imaging data were acquired in a 3T magnetic resonance imaging in EB and LB children (n = 40 each) and 30 sighted controls (SCs) and processed using CAT12 toolbox and FSL software. Two sample t-test was used for group analyses with P < 0.05 (false discovery rate-corrected). Increased CT in visual, sensory-motor, and auditory areas, and GI in bilateral visual cortex was observed in EB children. In LB children, the right visual cortex, anterior-cingulate, sensorimotor, and auditory areas showed increased GI. Structural- and tract-based spatial statistics changes were observed in anterior visual pathway, thalamo-cortical, and corticospinal tracts, and were correlated with education onset and global cognition in EB children. Reduced impairment in WM, increased CT and GI and its correlation with global cognitive functions in visually impaired children suggests cross-modal plasticity due to adaptive compensatory mechanism (as compared to SCs). Reduced CT and increased FA in thalamo-cortical areas in EB suggest synaptic pruning and alteration in WM integrity. In the visual cortical pathway, higher education and the development of blindness modify the morphology of brain areas and influence the probabilistic tractography in EB rather than LB.

Frontal lobe metabolic alterations characterizing Parkinson's disease cognitive impairment.

BACKGROUND AND PURPOSE: Diagnosis of Parkinson's disease (PD) cognitive impairment at early stages is challenging compared to the stage of PD dementia where functional impairment is apparent and easily diagnosed. Hence, to evaluate potential early stage cognitive biomarkers, we assessed frontal lobe metabolic alterations using in vivo multi-voxel proton magnetic resonance spectroscopic imaging (1H-MRSI). METHOD: Frontal metabolism was studied in patients with PD with normal cognition (PD-CN) (n = 26), with cognitive impairment (PD-CI) (n = 27), and healthy controls (HC) (n = 30) using a single slice (two-dimensional) 1H-MRSI at 3 T. The acquired spectra were post-processed distinctly for voxels corresponding to the bilateral middle/superior frontal gray matter (GM) and frontal white matter (WM) regions (delineated employing neuromorphometrics atlas) using the LC-Model software. RESULT: Significant (post hoc p < 0.016) reduction in the concentration of N-acetyl aspartate (NAA) in the middle and superior frontal GMs and total choline (tCho) and total creatine (tCr) in the frontal WM was observed in PD-CI compared to PD-CN and HC, while that in HC and PD-CN groups were comparable. The NAA and tCr/tCho metabolite concentrations showed significant (p < 0.05) positive correlations with cognitive test scores in the frontal GM and WM, respectively. The receiver operating curve (ROC) analysis revealed significant (p < 0.05) "area under curve" for NAA/tNAA in the frontal GM and tCho in the frontal WM. CONCLUSION: The frontal metabolic profile is altered in cognitively impaired PD compared with cognitively normal PD. Neuronal function loss (NAA), altered energy metabolism (Cr), and cholinergic (Cho) neural transmission are implicated in PD cognitive pathology. Frontal neuro-metabolism may promisingly serve as PD cognitive biomarker.

Cortical thickness and gyrification index measuring cognition in Parkinson's disease.

OBJECTIVE: Cortical dynamics is driven by cortico-cortical connectivity and it characterizes cortical morphological features. These brain surface features complement volumetric changes and may offer improved understanding of disease pathophysiology. Hence, present study aims to investigate surface features; cortical thickness (CT) and gyrification index (GI) in Parkinson's disease (PD) patients of normal cognition (PD-CN), cognitively impaired patients with PD (PD-CI) in comparison with cognitively normal healthy controls (HC) to better elucidate cognition linked features in PD. METHOD: Anatomical MRI (3DT1) was carried out in 30 HC (56.53 ± 8.42 years), 30 PD-CN (58.8 ± 6.07 years), and 30 PD-CI (60.3 ± 6.43 years) subjects. Whole brain ROI based parcellation using Desikan-Killiany (DK-40) atlas followed by regional CT and GI differentiation [with 'age' and 'total intracranial volume' (TIV) correction], multiple linear regression (with 'age', 'TIV', and 'education' correction) with clinical variables, ROC analysis, and CT-GI correlation across the groups was used for data analysis. RESULTS: Widespread cortical thinning with regional GI reduction was evident in PD-CI with respect to other two groups (HC and PD-CN), and with absence of such alterations in PD-CN compared to HC. Frontal, parietal, and temporal CT/GI significantly correlated with cognition and presented classification abilities for cognitive state in PD. Mean regional CT and GI were found negatively correlated across groups with heterogeneous regions. CONCLUSION: Fronto-parietal and temporal regions suffer cognition associated cortical thinning and GI reduction. CT may serve better discriminator properties and may be more consistent than GI in studying cognition in PD. Heterogeneous surface dynamics across the groups may signify neuro-developmental alterations in PD.

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.

Effect of Doxorubicin on Squamous Cell Carcinoma of Skin: Assessment by MRI Relaxometry at 4.7T.

Squamous cell carcinoma (SCC) of skin has no standard treatment regimen, resulting in recurrences/metastasis. Although, doxorubicin (Dox), an anthracycline antibiotic has demonstrated some degree of efficacy. Molecular imaging can help in assessment of treatment response and prognosis of SCCs. MRI data showed that spin-spin relaxation (T2) time was longer (138 ± 2 msec) in Dox treated Test-II and there is no significant difference in spin-lattice relaxation (T1) time with respective controls. These findings further corroborated with the histology, proliferation index, apoptotic index, and HMGA1 protein expression. Thus, MRI may be a useful tool for monitoring treatment response noninvasively for skin tumor prognosis.

Auditory perception of ambiguous and non-ambiguous sound in early and late blind children: A functional connectivity study.

INTRODUCTION: Auditory perception and associated cognition involve visual and auditory cortical areas for inference of meaningful soundscape. OBJECTIVE: To investigate auditory perception of ambiguous and non-ambiguous stimulation in auditory and visual cortical networks for categorical discrimination. METHODOLOGY: Functional mapping was carried out in twenty early (EB), twenty late blind (LB) and fifteen healthy children, during auditory ambiguous and non-ambiguous stimulation task in a 3 T MR scanner to estimate hemodynamic signal alteration and its effect on functional connectivity. The degree of amplitude low-frequency fluctuation (ALFF), correlation analysis and multiple comparison was carried out to map the impact of duration of education and onset of blindness (EB and LB). RESULTS AND DISCUSSION: Increased functional connectivity (FC) and cross-modal reorganization was observed in auditory, visual and language networks in EB children. FC was increased in contralateral hemisphere in both the blind children (EB and LB) groups and was positively correlated with duration of education performance. Cognitive assessment scores correlated (p < 0.01) with cluster coefficient of FC and BOLD response. CONCLUSION: FC alterations depend on onset age and audio-haptic training in children associated with increased auditory language and memory perception.

Neurochemical correlates of cognitive functions in euthymic patients with bipolar disorder: 1H-MRS study.

OBJECTIVES: We assessed and correlated neurochemical levels and cognitive functions in left dorsolateral prefrontal cortex (DLPFC) and left hippocampus in euthymic patients with bipolar disorder and compared these with healthy controls METHODOLOGY: Twenty-five right-handed euthymic patients (HAM-D score < 7, and YMRS score < 7) with bipolar disorder and 20 age and gender matched controls were compared for neurometabolites (n-acetylaspartate - tNAA, choline - Cho, creatinine - Cr, myoinositol - Ins, and glutamine/glutamate - Glu/Gln) measured in left DLPFC and left hippocampus using single voxel magnetic resonance spectroscopy (MRS) and cognitive functions assessed using trail making test (TMT - A and B), wisconsin card sorting test (WCST), and wechsler memory scale (WMS-III Indian adaptation). RESULTS: The two groups were comparable on socio-demographic variables. tNAA levels in DLPFC and hippocampus, and glutamate levels in hippocampus were found to be significantly lower and Inositol and glutamine levels in hippocampus were found to be significantly higher in patients as compared to controls. Patients performed significantly poorly as compared to controls on TMT A & B, all subscales of WMS - III, 5 subscales of WCST, including perseverative responses and errors. The tNAA and glutamate levels in left DLPFC in patients correlated with scores on TMT A & B, and several subscales of WCST and WMS-III. tNAA concentration in left hippocampus in patients correlated with scores on subscales of WMS-III. CONCLUSION: Neurochemical dysfunction in select brain areas directly correlates with impairment in cognitive functions seen in patients with bipolar disorder in euthymic phase.

Cognitive Performance and Neuro-Metabolites in HIV Using 3T Magnetic Resonance Spectroscopy: A Cross-Sectional Study from India.

BACKGROUND: Cognitive impairment in patients with human immunodeficiency virus (HIV) is associated with higher morbidity. The prevalence of the metabolite changes in the brain associated with cognitive impairment in anti-retroviral therapy naïve patients with HIV is unknown. OBJECTIVE: To estimate the prevalence of the neurometabolites associated with cognitive impairment in antiretroviral therapy (ART) naïve patients with HIV. METHODS: We conducted a cross-sectional study among ART naïve patients with HIV aged 18-50 years in a tertiary care center in India. Cognition was tested using the Post Graduate Institute battery of brain dysfunction across five domains; memory, attention-information processing, abstraction executive, complex perceptual, and simple motor skills. We assessed the total N-acetyl aspartyl (tNAA), creatine (tCr) and glutamate + glutamine (Glx) using 3T magnetic resonance spectroscopy. Cognitive impairment was defined as an impairment in ≥2 domains. RESULTS: Among 43 patients eligible for this study, the median age was 32 years (IQR 29, 40) and 30% were women. Median CD4 count and viral load were 317 cells/µL (IQR 157, 456) and 9.3 copies/ µL (IQR 1.4, 38), respectively. Impairment in at least one cognitive domain was present in 32 patients (74.4%). Impairment in simple motor skills and memory was present in 46.5% and 44% of patients, respectively. Cognitive impairment, defined by impairment in ≥2 domains, was found in 22 (51.2%) patients. There was a trend towards higher concentration of tNAA (7.3 vs. 7.0 mmol/kg), tGlx (9.1 vs. 8.2 mmol/kg), and tCr (5.5 vs. 5.2 mmol/kg) in the frontal lobe of patients with cognitive impairment vs. without cognitive impairment but it did not reach statistical significance (p>0.05 for all). There was no difference in the concentration of these metabolites in the two groups in the basal ganglia. CONCLUSION: There is a high prevalence of cognitive impairment in ART naïve patients with HIV. There is no difference in metabolites in patients with or without cognitive impairment. Further studies, with longitudinal follow-up are required to understand the underlying pathophysiological mechanisms.

Effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in vitamin D-deficient Asian Indians: a randomized, controlled trial.

CONTEXT: Vitamin D deficiency is prevalent worldwide. Vitamin D supplementation has shown variable effect on skeletal muscle strength in the elderly with hypovitaminosis D. There is a paucity of similar data in young individuals. OBJECTIVE: To study the effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in young individuals. SUBJECTS: Forty healthy volunteers (24 M/16 F, mean age (SD) 31.5 ± 5.0 year) with hypovitaminosis D were randomized to either oral cholecalciferol (60,000 IU D3/week for 8 weeks followed by 60,000 IU/month for 4 months) with 1 g of elemental calcium daily or dual placebos for 6 months. MEASUREMENTS: Handgrip and gastro-soleus dynamometry, pinch-grip strength, respiratory pressures, 6-min walk-test and muscle energy metabolism on (31) P magnetic resonance spectroscopy were assessed at baseline and after 6 months. RESULTS: The mean serum 25(OH)D in the supplemented and placebo groups at baseline, two and 6 months were 25.4 ± 9.9, 94.5 ± 53.8 and 56.0 ± 17.0 nm, and 21.1 ± 9.4, 32.8 ± 14.4 and 29.7 ± 15.0 nm, respectively. The supplemented group gained a handgrip strength of 2.4 kg (95% C.I. = 1.2-3.6); gastro-soleus strength of 3.0 Nm (95% C.I. = 0.1-5.9) and walking distance of 15.9 m (95% C.I. = 6.3-25.5) over the placebo group after adjustment for age, gender and respective baseline parameters. Muscle energy parameters were comparable at 6 months. CONCLUSIONS: Six months of cholecalciferol and calcium supplementation results in enhanced skeletal muscle strength and physical performance despite no change in muscle energy parameters. Cholecalciferol supplementation of 60,000 IU per month could not maintain 25(OH)D levels in the sufficient range.

Proton magnetic resonance spectroscopy of brain in obstructive sleep apnoea in north Indian Asian subjects.

BACKGROUND & OBJECTIVES: Repeated apnoeic/hypoapnoeic episodes during sleep may produce cerebral damage in patients with obstructive sleep apnoea (OSA). The aim of this study was to determine the absolute concentration of cerebral metabolites in apnoeic and non-apnoeic subjects from different regions of the brain to monitor the regional variation of cerebral metabolites. METHODS: Absolute concentration of cerebral metabolites was determined by using early morning proton magnetic resonance spectroscopy ((1)H MRS) in 18 apnoeic patients with OSA (apnoeics) having apnoea/hypopnoea index (AHI) >5/h, while 32 were non-apnoeic subjects with AHI< 5/h. RESULTS: The absolute concentration of tNAA [(N-acetylaspartate (NAA)+N-acetylaspartylglutamate (NAAG)] was observed to be statistically significantly lower (P<0.05) in apnoeics in the left temporal and left frontal gray regions compared to non-apnoeics. The Glx (glutamine, Gln + glutamate, Glu) resonance showed higher concentration (but not statistically significant) in the left temporal and left frontal regions of the brain in apnoeics compared to non-apnoeics. The absolute concentration of myo-inositol (mI) was significantly high (P<0.03) in apnoeics in the occipital region compared to non-apnoeics. INTERPRETATION & CONCLUSIONS: Reduction in the absolute concentration of tNAA in apnoeics is suggestive of neuronal damage, probably caused by repeated apnoeic episodes in these patients. NAA showed negative correlation with AHI in the left frontal region, while Cho and mI were positively correlated in the occipital region and Glx showed positive correlation in the left temporal region of the brain. Overall, our results demonstrate that the variation in metabolites concentrations is not uniform across various regions of the brain studied in patients with OSA. Further studies with a large cohort of patients to substantiate these observations are required.

Magnetic resonance imaging evaluation of subarachnoid hemorrhage in rats and the effects of intracisternal injection of papaverine and nitroglycerine in the management of cerebral vasospasm.

BACKGROUND: Cerebral vasospasm is a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). It usually occurs about 3-9 days after SAH. The pathogenesis involves the release of endogenous spasmogens. Though various treatment modalities are available, none are really effective. AIMS AND OBJECTIVES: The aim of the study was to develop an effective animal model for the study of SAH and vasospasm as well as to study the efficacy of vasodilators, namely nitroglycerine and papaverine, on SAH-induced vasospasm using magnetic resonance angiography. MATERIALS AND METHODS: Fifteen Wistar albino rats, weighing around 150-200 gm were used for the study. Five rats served as controls of SAH-induced vasospasm, while five rats each were used to study the efficacy of intracisternal injection of papaverine or nitroglycerine. RESULTS: Rats demonstrate vasospasm in a manner similar to humans. The maximal vasospasm is seen in the basilar artery. Statistical analysis demonstrates an improvement in vasospasm after instillation of intracisternal papaverine at the end of 2 hours in basilar and left internal cerebral artery. However, nitroglycerine does not produce any significant amelioration of vasospasm. Thus, it can be deduced that the pathogenesis of the vasospasm is more due to the action of cGMPase enzyme rather than inhibition of nitric oxide (NO) synthetase by the spasmogens. The present study is the first study in the English literature to compare the effects of single bolus doses of nitroglycerine and papaverine using magnetic resonance angiography. CONCLUSION: Rats can be used to create an effective model for SAH-induced vasospasm as the pattern resembles human SAH. Papaverine is an effective drug for ameliorating SAH-induced vasospasm. Short-acting NO donors are not as effective in ameliorating vasospasm.

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.

Effect of vineatrol in focal cerebral ischemia in rats.

The present study was carried out to examine the effect of administration of vineatrol in the middle cerebral artery (MCA) occlusion model of stroke in rats. Rats were anesthetized using chloral hydrate (400 mg/kg i.p.) and subjected to 2 h of transient MCA occlusion. Vineatrol was administered at doses of 10, 20 and 40 mg/kg i.p. to different groups. In total, four injections of vineatrol were given, i.e., at the time of MCA occlusion, 1 h after MCA occlusion, at the time of reperfusion and 30 min after reperfusion. Neurological deficit and motor performance tests (grip, foot fault, rotarod performance, spontaneous locomotor activity tests) were carried out 24 h after MCA occlusion. Thereafter, the rats were sacrificed to estimate markers of oxidative stress: malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD). A vehicle-treated group was also run in parallel. Vineatrol at the dose of 10 mg/kg i.p. neither improved neurological deficits nor decreased the elevated level of MDA compared with vehicle-treated MCA-occluded rats. However, higher doses of vineatrol (20 and 40 mg/kg i.p.) afforded significant protection, as shown by the increase in scoring on motor performance tests and significant attenuation of the elevated MDA level observed after MCA occlusion. Levels of GSH and SOD were significantly increased. The results demonstrate that administration of vineatrol is able to reduce the neuronal damage caused by focal ischemia in the MCA occlusion model of stroke in rats.

Proton magnetic resonance spectroscopy of brain to study the cerebral metabolic abnormalities in COPD patients: a case control study in north India.

BACKGROUND: To investigate changes in the cerebral metabolism of nondiabetic and normolipidaemic patients with chronic obstructive pulmonary disease (COPD) using localised in vivo proton magnetic resonance spectroscopy (1H MRS), and to correlate these with the severity of disease. METHODS: Twenty-eight symptomatic COPD patients and 19 healthy controls underwent 1H MRS of brain, pulmonary function testing and respiratory muscle strength evaluation. The parieto-temporal and occipital regions were localised for 1H MRS. The metabolic ratios of N-acetyl aspartate to cretinine (NAA/Cr) and choline containing compound to creatinine (Cho/Cr) were calculated by integrating area under the each peak. RESULTS: The mean value of NAA/Cr and Cho/Cr in parieto-temporal area in COPD patients were (1.86 +/- 0.54) and (0.77 +/- 0.23), respectively. The mean values of NAA/Cr and Cho/Cr in occipital area in COPD patients were (1.75 +/- 0.44) and (0.61 +/- 0.25), respectively. Compared with healthy control subjects, the mean values of Cho/Cr in COPD patients were lower, both in parieto-temporal (0.77 +/- 0.23 vs. 0.89 +/- 0.35; p = 0.17) and occipital (0.61 +/- 0.25 +/- vs. 0.67 +/- 0.08; p = 0.36) areas of the brain. CONCLUSIONS: The cerebral metabolism, pulmonary function testing and respiratory muscle strength altered in symptomatic COPD patients. The clinical significance of cerebral metabolic changes in COPD patients needs to be further investigated.

Neuro-protective effect of monomethyl fumarate on ischemia reperfusion injury in rats: Role of Nrf2/HO1 pathway in peri-infarct region.

Post stroke recanalization has been associated with increased risk of oxidative stress. Stimulating endogenous antioxidant pathway by activation of nuclear factor erythroid-2-related factor-2 (Nrf2) plays a key role in neuronal defense against inflammation and oxidative stress in penumbra. Here, we explored whether monomethyl fumarate (MMF) could produce neuro-protection after ischemia/reperfusion (I/R) injury via Nrf2/HO1 activation. In male SD rats, middle cerebral artery was occluded for 90 min and confirmed using Laser Doppler flowmeter. MMF (10, 20 and 40 mg/kg) was administered in two divided doses at 30 min post ischemia and 5-10 min after reperfusion. After 24 h, effect on neurobehavioral parameters, infarct damage by TTC staining and MRI, oxidative stress and inflammatory cytokines were assessed. Expression studies of nuclear Nrf2 and cytoplasmic HO1 were performed in peri-infarct cortex and striatum; followed by dual immunofluorescence study to check the specific cell type. I/R induced neurobehavioral deficits and infarct damage were significantly (p < 0.05) attenuated by MMF (20 and 40 mg/kg). MMF, 20 mg/kg, significantly normalized I/R induced altered redox status and increased levels of TNF-α, IL-1ß in the ipsilateral cortex. MRI data showed significantly reduced infarct in cortex but not in striatum after MMF treatment. Expression of nuclear Nrf2 and cytoplasmic HO1 were significantly (p < 0.05) increased in peri-infarct cortex after treatment with MMF. Additionally, dual immunofluorescence showed increased Nrf2 expression in neurons and HO1 expression in neurons as well as astrocytes in peri-infarct cortex after MMF treatment. Our results show the neuro-protective potential of MMF probably by restricting the progression of damage from striatum to cortex through activation of Nrf2/HO1 pathway in peri-infarct cortex.

Structural elucidation of 4'-epiadriamycin by nuclear magnetic resonance spectroscopy and comparison with adriamycin and daunomycin using quantum mechanical and restrained molecular dynamics approach.

The structural and electronic properties of 4'-epiadriamycin, adriamycin, and daunomycin have been studied using density functional theory (DFT) employing B3LYP exchange correlation. The chemical shifts of (1)H and (13)C resonances in nuclear magnetic resonance spectra have been calculated using Gauge-Invariant Atomic Orbital (GIAO) method as implemented in Gaussian 98 and compared with experimental spectra recorded at 500 MHz. (13)C resonances of drugs have been assigned for the first time. A restrained molecular dynamics approach was used to get the optimized solution structure of drugs using inter-proton distance constraints obtained from 2D NOESY spectra. The glycosidic angle C7-O7-C1'-C2' is found to show considerable flexibility by adopting 156 degrees -161 degrees (I), 142 degrees -143 degrees (II), and 38 degrees -78 degrees (III) conformations, of which the biological relevant structure appears to be the conformer II. The observed different conformations of the three drugs are correlated to the differential anticancer activity and the available biochemical evidence exhibited by these drugs.

Curcuma oil: reduces early accumulation of oxidative product and is anti-apoptogenic in transient focal ischemia in rat brain.

Turmeric is a source of numerous aromatic compounds isolated from powdered rhizomes of Curcuma longa Linn. The constituents are present as volatile oil, the Curcuma oil (C.oil), semi-solid oleoresins and non-volatile compounds such as curcumin. A rapidly expanding body of data provides evidence of the anti-cancer action of Curcumin, and most importantly in the present context, its neuroprotective activity. Almost nothing is known about such activity of C.oil. We report that C.oil (500 mg Kg(-1) i.p.) 15 min before 2 h middle cerebral artery occlusion (MCAo) followed by 24 h reflow in rats significantly diminished infarct volume, improved neurological deficit and counteracted oxidative stress. The percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated. Mitochondrial membrane potential, reactive oxygen species, peroxynitrite levels, caspase-3 activities leading to delayed neuronal death were significantly inhibited after treatment with C.oil. These results suggest that the neuroprotective activity of C.oil against cerebral ischemia is associated with its antioxidant activities and further; there is attenuation of delayed neuronal death via a caspase-dependent pathway. C.oil appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other disorders associated with oxidative stress.

In vivo proton spectroscopy of giant cell tumor of the bone.

OBJECTIVE: The proton MR spectroscopic finding of elevated choline has been reported to be useful in the differentiation of malignant from benign musculoskeletal tumors. This study was designed to evaluate the MR spectroscopy features of giant cell tumor (GCT) of the bone, primarily to determine whether the presence of choline is a frequent occurrence in these tumors and whether MR spectroscopy features can be correlated with clinical, radiologic, and histopathologic findings. SUBJECTS AND METHODS: MRI, dynamic contrast-enhanced MRI, and proton MR spectroscopy were performed in 33 patients with bone tumors on a 1.5-T MR scanner. Of these, 12 patients who had GCT of the bone form the subject material for this study. Dynamic contrast-enhanced MRI and single-voxel proton MR spectroscopy were performed after preliminary evaluation with radiography. Patients were divided into two groups, those with elevated choline levels and those without a choline peak on MR spectroscopy. The clinical and radiologic features, including the Campanacci stage and dynamic MRI findings, were compared in these two groups. Core biopsy was performed in all patients, and in 10 of 12 patients, histopathologic evaluation of the postoperative resected specimen was also performed. RESULTS: Although all 12 tumors were benign on histopathology, four had elevated choline levels. Of these, three (75%) had an aggressive radiographic appearance (Campanacci stage 3). As opposed to this, only three of the eight (37.5%) tumors without a choline peak had an aggressive radiographic appearance. Except for a single case, all tumors showed early enhancement and washout of contrast material on dynamic MRI. CONCLUSION: The results of this study indicate that GCT of bone may show raised choline levels on proton MR spectroscopy. This finding is not an indicator of malignancy in these tumors.

Neuroprotective efficacy and therapeutic window of curcuma oil: in rat embolic stroke model.

BACKGROUND: Among the naturally occurring compounds, turmeric from the dried rhizome of the plant Curcuma longa has long been used extensively as a condiment and a household remedy all over Southeast Asia. Turmeric contains essential oil, yellow pigments (curcuminoids), starch and oleoresin. The present study was designed for investigating the neuroprotective efficacy and the time window for effective therapeutic use of Curcuma oil (C. oil). METHOD: In the present study, the effect of post ischemic treatment of C.oil after ischemia induced by occlusion of the middle cerebral artery in the rat was observed. C.oil (500 mg/kg body wt) was given 4 hrs post ischemia. The significant effect on lesion size as visualized by using diffusion-weighted magnetic resonance imaging and neuroscore was still evident when treatment was started 4 hours after insult. Animals were assessed for behavioral deficit scores after 5 and 24 hours of ischemia. Subsequently, the rats were sacrificed for evaluation of infarct and edema volumes and other parameters. RESULTS: C.oil ameliorated the ischemia induced neurological functional deficits and the infarct and edema volumes measured after 5 and 24 hrs of ischemia. After 24 hrs, immunohistochemical and Western blot analysis demonstrated that the expression of iNOS, cytochrome c and Bax/Bcl-2 were altered after the insult, and antagonized by treatment with C.oil. C.oil significantly reduced nitrosative stress, tended to correct the decreased mitochondrial membrane potential, and also affected caspase-3 activation finally apoptosis. CONCLUSION: Here we demonstrated that iNOS-derived NO produced during ischemic injury was crucial for the up-regulation of ischemic injury targets. C.oil down-regulates these targets this coincided with an increased survival rate of neurons.

Brain areas activated after ejaculation in healthy young human subjects.

Brain mechanisms for the refractory period that characteristically follows ejaculation in animals and human are poorly understood. The possibility of active inhibition of brain areas being responsible for the post-ejaculatory inhibitory state has not been ruled out. Using Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) we have mapped brain areas in healthy young volunteers immediately after ejaculation. Functional imaging of the brain for 30 minutes beginning after three minutes of ejaculation induced by masturbation showed spatio-temporal activation in amygdala, temporal lobes and septal areas. The septal areas were observed to be active for a shorter duration than the amygdala and the temporal lobe. Thus the temporal sequence of involvement of the above neural structures may contribute to temporary inhibition of sexual arousal/penile erection during the post-ejaculatory refractory period in humans.