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Background/Aims Irritable bowel syndrome (IBS) is associated with exaggerated cerebral response including emotional processing following visceral stimulation; though data on this issue is available in female IBS patients, it is scanty among males. Hence, we aimed to study brain response of male IBS patients following rectal balloon distension as compared to healthy controls using functional magnetic resonance imaging (fMRI). Data between diarrhea and constipation predominant IBS (IBS-D and IBS-C) were also compared. Methods Rectal balloon distension threshold was assessed in 20 male IBS patients (10 IBS-C and 10 IBS-D) and 10 age-matched male healthy controls. Subsequently, fMRI on all the participants was performed at their respective rectal pain threshold. The fMRI data were analysed using the Statistical Parametric Mapping software. Results IBS patients showed greater cerebral activations in insula, middle temporal gyrus, and cerebellum in the left hemisphere compared to healthy controls. Neural activation was found in bilateral precuneus/superior parietal lobules in controls but not in patients with IBS. The brain activation differed among IBS-C and IBS-D patients; while the right mid-cingulate cortex was activated in IBS-C, the left inferior orbito-frontal cortex, left calcarine, and bilateral fusiform gyri were activated among patients with IBS-D following rectal balloon distension. Conclusions Brain response to rectal balloon distension differed among male patients with IBS and controls and among patients with IBS-C and IBS-D. Differential activation among patients with IBS-C and IBS-D was seen in the brain regions controlling affective motivation, homeostatic emotions, and autonomic responses to pain. (J Neurogastroenterol Motil 2017;23:415-427)

Takayasu arteritis (TA) is a debilitating, systemic disease that involves the aorta and large arteries in a chronic inflammatory process that leads to vessel stenosis. Initially, the disease remains clinically silent (or remains undetected) until the patients present with vascular occlusion. Therefore, new methods for appropriate and timely diagnosis of TA cases are needed to start proper therapy on time and also to monitor the patient's response to the given treatment. In this context, NMR-based serum metabolomic profiling has been explored in this proof-of-principle study for the first time to determine characteristic metabolites that could be potentially helpful for diagnosis and prognosis of TA. Serum metabolic profiling of TA patients (n = 29) and healthy controls (n = 30) was performed using 1D (1)H NMR spectroscopy, and possible biomarker metabolites were identified. Using projection to least-squares discriminant analysis, we could distinguish TA patients from healthy controls. Compared to healthy controls, TA patients had (a) increased serum levels of choline metabolites, LDL cholesterol, N-acetyl glycoproteins (NAGs), and glucose and (b) decreased serum levels of lactate, lipids, HDL cholesterol, and glucogenic amino acids. The results of this study are preliminary and need to be confirmed in a prospective study.

Metabolite analysis of peritoneal dialysis (PD) effluent may provide information regarding onset and progression of complications associated with prolonged PD therapy. In this context, the nuclear magnetic resonance detectable small metabolites of PD effluent samples were characterised using high-resolution 1H and 1H–13C NMR spectroscopy. The various spectra were recorded (at 800 MHz proton frequency) on PD effluent samples obtained after 4-h (intraperitoneal) dwell time from patients with end-stage renal failure and continuing normally on PD therapy. In spite of devastating spectral feature of PD effluent due to the presence of intense resonances from glucose and lactate, we were able to identify 53 small endogenous metabolites (including many complex coupled spin systems) and more than 90% of the total CH cross peaks of 1H–13C heteronuclear single-quantum correlation spectrum specific to various metabolites of PD effluent. We foresee that the characteristic fingerprints of various metabolites of control PD effluent samples will be used to identify and distinguish metabolic differences from PD-related complications. Copyright © 2014 John Wiley & Sons, Ltd.

The effect of "SOHAM" meditation has been investigated using functional magnetic resonance imaging (fMRI) in long-term meditators while they were meditating and not meditating. The results have revealed activation in left middle prefrontal cortex (MPFC) (Brodmann's area, BA 46), left inferior frontal gyrus (LIFG) (BA 44), left supplementary motor area (SMA) (BA 6) and left precuneus (BA 5) during the meditation period compared to the control period (no-meditation period). The results have been interpreted in terms of regulation of the emotional state, attention and working memory of the meditators.

The anatomical correlates of long-term meditators involved in practice of "SOHAM" meditation have been studied using voxel-based morphometry (VBM). The VBM analysis indicates significantly higher gray matter density in brain stem, ventral pallidum, and supplementary motor area in the meditators as compared with age-matched nonmeditators. The observed changes in brain structure are compared with other forms of meditation.

Background Fulminant hepatic failure is associated with liver metabolic derangements which could have fatal consequences. The aim of the present study is to identify serum markers for early prediction of the outcome. Methods Proton nuclear magnetic resonance spectroscopic studies of serum of fulminant hepatic failure patients due to viral hepatitis with grade II/III of encephalopathy (twenty-four: ten prospective and fourteen retrospective) and twenty-five controls were undertaken. Of the twenty-four patients, fifteen survived with medical management alone while nine had fatal outcome. Results The results demonstrated significantly elevated indices of amino acids (alanine, lysine, glutamine, histidine, tyrosine, phenylalanine and 1,2-propanediol) in fatal cases compared to survivors and controls. Principal component analysis showed clear separation of fatal and surviving cases. Liver function parameters were significantly deranged in patients but they failed to provide early significant differences between surviving and fatal cases. Compared to Model for End-stage Liver Disease scores, Principal Component Analysis appear to be better as an early prognostic indicator. Biochemical mapping of pathways suggested interruptions in amino acid metabolism and urea cycle. Conclusions Proton nuclear magnetic resonance studies of serum have the potential of rapidly identifying patients with irreversible fulminant hepatic failure requiring liver transplantation as life saving option.

Management of patient with Lupus Nephritis (LN) continues to remain a challenge for the treating physicians because of considerable morbidity and even mortality. The search of biomarkers in serum and urine is a focus of researchers to unravel new targets for therapy. In the present study, the utility of NMR-based serum metabolomics has been evaluated for the first time in discriminating LN patients from non-nephritis lupus patients (SLE) and further to get new insights into the underlying disease processes for better clinical management. Metabolic profiling of sera obtained from 22 SLE patients, 40 LN patients and 30 healthy controls (HC) were performed using high resolution 1D 1H-CPMG and diffusion edited NMR spectra to identify the potential molecular biomarkers. Using multivariate analysis, we could distinguish SLE and LN patients from HC and LN from SLE patients. Compared to SLE patients, the LN patients had increased serum levels of lipid metabolites (including LDL/VLDL lipoproteins), creatinine and decreased levels of acetate. Our results revealed that metabolic markers especially lipids and acetate derived from NMR spectroscopy has high sensitivity and specificity to distinguish LN among SLE patients and has the potential to be a useful adjunctive tool in diagnosis and clinical management of LN.

The small chemical shift dispersion and complex multiplicity pattern in proton NMR limit quantifications, for instance the determination of enantiomeric excess (ee) for an enantiomeric mixture. Herein, we present a simple proton-proton correlation experiment with band selective homonuclear (BASH) decoupling in both F

Prolonged biliary obstruction and infection cause retention of biliary constituents in liver followed by hepatocyte dysfunction. Decompression therapy is important for both management and prognostic reasons and restores hepatocyte function. Quantitative metabolite profiling of bile using NMR spectroscopy at the time of obstruction and serially following decompression therapy using percutaneous transhepatic biliary drainage (PTBD) from nineteen patients with extrahepatic malignant biliary obstruction are presented. Based on detailed history, clinical condition, total leucocyte counts (TLC) and microbiological cultures of bile, patients were classified in two groups depending upon absence or presence of cholangitis. Statistical analysis was performed for comparison within each group using Wilcoxan sign square rank test. TLC and liver function tests indicated a trend towards recovery following decompression by one week. While on day 0 biliary constituents were undetectable in both the groups of patients, they increased significantly following one week of drainage with better recovery in patients with cholangitis compared to without. Free amino acids' signals were detected in all specimens starting from day 1 after decompression. This indicates disruption of blood-bile barrier during cholestasis and slow restoration of tight junction of hepatocytes following decompression leading to the appearance of biliary constituents in bile. Decompression therapy tends to restore biliary constituents with a prompt recovery in patients with cholangitis further supports such therapy for clinical management and outcome. To our knowledge this is the first report on the detection of amino acids in bile taken from common bile duct though they have been reported in hepatic bile.

Pus samples obtained from 109 patients with liver abscess were examined by NMR spectroscopy. To our knowledge this is the first report on metabolic profiling of liver abscesses. Fifty metabolites were identified by combination of one (1D) and two-dimensional (2D) NMR spectra. Metabolic derangements were evaluated for differentiation between amoebic (ALA) and pyogenic liver abscess (PLA). The NMR results indicate that aspartate, asparagine and galactose, integral components of lipoproteophophoglycans (LPG) of the cell wall of Entamoeba histolytica are metabolic biomarkers of ALA. On the other hand, acetate, propionate, butyrate, succinate and formate, the fermentation products the facultative anaerobes are significantly prevalent in PLA. The NMR based metabolic profile of ALA and PLA are evaluated taking polymerase chain reaction (PCR) and bacterial culture as gold standard method. However, when NMR results were compared with culture and PCR methods, a correct diagnosis of 94.11% in ALA (n = 85) and 100% in PLA (n = 10) cases were observed. NMR spectroscopy in conjunction with PCR and culture can expedite in differentiating ALA from PLA.

Introduction Withania somnifera (Ashwagandha) is a high-value Ayurvedic medicinal plant and an important constituent of several dietary supplements. In order to substantiate the health claims, the herb has drawn considerable scientific attention. Objective The objective of the study was to investigate the alterations in primary and secondary metabolites of W. somnifera fruits during its maturity using NMR spectroscopy. Methodology Fruits at different stages of development from one week after fertilisation until maturity, classified in seven developmental stages, were analysed by a combined use of one- and two-dimensional NMR experiments. Results Seventeen metabolites were characterised and quantified from non-polar and polar extracts of different fruit development stages of W. somnifera. The principal component analysis of polar metabolites at different stages could be grossly classified into three metabolic phases, viz. initial phase, developmental phase and maturation phase. Conclusion Qualitative and quantitative analysis of metabolites in W. somnifera fruits indicated specific stages when fruits can be harvested for obtaining substantial bioactive ingredients for desirable pharmacological activity. This study potentially provides a complementary tool for quality control of herbal medicinal products when W. somnifera fruits are used. Copyright © 2011 John Wiley & Sons, Ltd.

Though tropical sprue (TS) is common in tropics, studies on small intestinal permeability (SIP) in TS are scant.SIP was evaluated using (1)H nuclear magnetic resonance (NMR) spectroscopy of urinary lactulose and mannitol in 24 patients with TS (22 before and 15 after treatment with tetracycline and folate) and in 31 healthy subjects (HS). Effect of treatment of TS on SIP and its relationship with outcome were studied.Subjects were comparable in terms of age and gender. Before treatment, urinary lactulose (0.24 mmol, 0-1.09 mmol versus 0.09 mmol, 0-0.68 mmol, P=0.02) and lactulose-to-mannitol (L/M) ratio (0.11, 0-0.41 versus 0.042, 0-0.26, P=0.001) were higher in TS than in HS, though mannitol was comparable (2.7 mmol, 0.61-10.5 mmol versus 3.8 mmol, 1.3-16.4 mmol, P=0.08). Patients improved after treatment [stool frequency (9, 4-20/day versus 1, 1-2/day, P0.0001), weight (44.4, 32-69 kg, versus 56, 39-84 kg, P0.0001), fecal fat (10.1, 6-26 g/24 h versus 4.4, 3.0-6.7 g/24 h, P0.0001), D-xylose (0.57, 0.28-1.2 g/5 g/5 h versus 1.1, 0.2-2.1 g/5 g/5 h, P0.0001), and small intestinal bacterial overgrowth (SIBO) resolved in 10/24 (41.7%) versus 1/15 (6.6%), P=0.02]. Though urinary lactulose (0.17, 0-4.3 mmol versus 0.09, 0-0.68 mmol, P=0.11) and mannitol (2.17, 0.8-36.7 mmol versus 3.84, 1.3-16.4 mmol, P=0.06) were comparable, L/M ratio was higher in TS than in HS (0.09, 0-0.22 versus 0.042, 0-0.26, P=0.002). L/M ratio was more often abnormal (cutoff 0.078) in TS than in HS [14/22 (63.6%) versus 3/31 (9.7%); P=0.0001], which persisted even after treatment [9/15 (60%) as compared with HS; P=0.0006]. Persistently abnormal SIP was associated with less weight gain and frequent stools following treatment.SIP is often abnormal in TS and remains unchanged even after successful treatment that was associated with less weight gain and more frequent stool.

Alterations in the anatomical structures, sap translocation and metabolic profiles in Jatropha curcas L. (Euphorbiaceae), infected with Jatropha mosaic virus (JMV) have been investigated using MRI and HR-MAS NMR spectroscopy. The contrast of MRI images distinguishes abnormalities in anatomical structures of infected and healthy stem. The HR-MAS NMR spectroscopic analysis indicated that viral infection significantly affected the plant metabolism. Higher accumulation of TCA cycle intermediates, such as citrate and malate, in JMV-infected plants suggested a higher rate of respiration. The respiration rate was more than twofold as compared to healthy ones. The viral stress also significantly increases the concentrations of alanine, arginine, glutamine, valine, GABA and choline as compared to healthy ones. Microscopic examination revealed severe hyperplasia caused by JMV with a considerable reduction in the size of stem cells. Lower concentration of glucose and sucrose in viral-infected stem tissues indicates decreased translocation of photosynthates from leaves to stem due to hyperplasia caused by JMV. The MR images distinguished stele, cortical and pith regions of JMV-infected and healthy stems. Contrast of T(1)- and T(2)-weighted images showed significant differences in the spatial distribution of water, lipids and macromolecules in virus-infected and healthy stem tissues. The results demonstrated the value of MRI and HR-MAS NMR spectroscopy in studying viral infection and metabolic shift in plants. The present methodology may help in better understanding the metabolic alterations during biotic stress in other plant species of agricultural and commercial importance.

A method of choosing the correction factor based on Bloch equation for the quantitative estimation of metabolite from 1H NMR spectra recorded with reduced recycle delay is prescribed. The procedure reduces the experimental time without substantially compromising the accuracy of quantitative estimation. It is based on choosing the correction factors, which depend on T1 and T2 of the metabolite and recycle delay used for recording the spectra. It is validated by studying a mixture of amino acids with known concentration of constituents and human serum sample and it provides accuracy of quantitative estimation to 95–96%.

It is often difficult to distinguish benign ascites from malignant ascites by conventional examination of ascitic fluid. Therefore, (1)H NMR spectroscopy of ascitic fluid specimens was explored as a one-shot experiment to identify potentially interesting metabolic indices that might help to differentiate between the two. Seventy ascitic fluid specimens (15 cytologically positive for malignant cells, eight cytologically negative for malignant cells but remaining suspicious for malignant ascites, and 47 due to liver cirrhosis) were subjected to (1)H NMR spectroscopy for quantitative estimation of 14 metabolites. Mean concentrations of the metabolites were compared with the Mann-Whitney U test. Multivariate discriminant function analysis was performed to determine important descriptors in the discrimination process. The sensitivity and specificity of the proposed model were compared with conventional methods using ascitic fluid protein and serum ascitic albumin gradient. Then, probable predictions for the doubtful cases were made using the proposed model. Patients with malignant ascites had significantly higher mean concentrations (microM) of beta-hydroxybutyrate (594 vs 61), lactate (5384 vs 2104), acetone (136 vs 69), and acetoacetate (122 vs 48) than patients with cirrhotic ascites, and significantly lower concentrations of glutamine (359 vs 615), citrate (62 vs 118), glucose (4933 vs 8411), tyrosine (44 vs 124), and phenylalanine (51 vs 93) (P < 0.05 for all). In the discriminant function analysis model, the best discrimination (P < 0.001) was achieved when beta-hydroxybutyrate, lactate, citrate and tyrosine were considered together as markers. Sensitivity and specificity of the proposed model, ascitic fluid protein and serum ascitic albumin gradient were found to be 100% and 97.9%, 53.3% and 76.6%, and 60% and 87.2%, respectively. The proposed model put five of the eight doubtful cases in the malignant group. This is encouraging and may provide useful information for clinical purposes.

The influence of covalently attaching hydroxymethylene to the methyl groups of methyl-tri-n-alkylphosphonium halides (where the alkyl chains are decyl, tetradecyl, or octadecyl and the halide is chloride or bromide) or adding methanol as a solute to the salts on their solid, liquid-crystalline (smectic A2), and isotropic phases has been investigated using a variety of experimental techniques. These structural and compositional changes are found to induce liquid crystallinity in some cases and to enhance the temperature range and lower the onset temperature of the liquid-crystalline phases in some others. The results are interpreted in terms of the lengths of the three n-alkyl chains attached to the phosphorus cation, the nature of the halide anion, the influence of H-bonding interactions at the head group regions of the layered phases, and other solvent-solute interactions. The fact that at least 1 molar equiv of methanol must be added to effect complete (isothermal) conversion of a solid methyl-tri-n-alkylphosphonium salt to a liquid crystal demonstrates a direct and strong association between individual methanol molecules and the phosphonium salts. Possible applications of such systems are suggested.

We report here the measurement of the C-H and the H-H dipolar couplings of the methyl group of acetonitrile oriented in the biaxial liquid crystal potassium laurate/1-decanol/water system. These parameters show large variations when measured as a function of temperature. The variations follow the symmetry of the phase as the liquid crystal goes through the sequence of uniaxial - biaxial - uniaxial phases and show a close correspondence to the phase changes that occur in the liquid crystalline solvent coinciding with the onset of biaxiality. The H-C-H bond angle calculated after incorporating vibrational corrections to the dipolar couplings is discussed in terms of contributions in the case of the biaxial liquid crystal arising from vibration rotation interaction effects.(c) 2016 Elsevier B.V. All rights reserved.

Simple pulse-acquire NMR methods are presented for accurate quantitation of calcium (Ca(2+)), magnesium (Mg(2+)) and sodium (Na(+)) in human serum. Ca(2+) and Mg(2+) can be determined simultaneously by (1)H NMR via their EDTA (ethylenediaminetetraacetic acid) complexes. Spectra are acquired before and after addition of EDTA, and the difference spectrum is used for integration of the signals from the complexes relative to an internal reference. Serum sodium can also be determined through pulse-acquire (23)Na NMR by integration of the free sodium signal relative to a reference signal (Na(+)+EDTA in a coaxial capillary tube). The method shows excellent accuracy and precision for all three metal ions. Slow chemical exchange between complexed and free EDTA at the natural pH of serum does not limit the accuracy of the determination of Ca(2+) and Mg(2+), and the large errors associated with spin-echo spectral editing methods are avoided.

A high-resolution (1)H NMR study of serum and urine of fulminant hepatic failure patients (n = 22) [surviving (n = 12) and non-surviving (n = 10)] is reported. Glutamine in serum and urine glutamine:creatinine ratio were higher in non-surviving patients compared with surviving patients [serum glutamine, 3.08 (1.68-7.11) vs 0.56 (0.34-0.99) mM, median and range; p = 0.0001 and urine glutamine:creatinine ratio, 1.72 (0.24-7.76) vs 0.39 (0.1-0.84), p = 0.1], and urine urea:creatinine ratio was higher in surviving patients compared with non-surviving patients [10.83 (0.2-22.6) vs 2.09 (0.96-4.0), p = 0.002]. On the other hand, no significant differences were found in the conventionally employed clinical parameters such as serum alanylaminotransferase, aspartylaminotransferase and bilirubin except prothrombin time (p = 0.02). The difference in serum glutamine and urine urea was significant in the two categories of patients and distinctly different values of serum glutamine for both the categories of patients correctly predicted the outcome. These results promise immense potential for NMR spectroscopy in rapidly deciding on the need for advanced therapeutic intervention such as artificial liver support or emergency liver transplantation in FHF.

The utility of 1H NMR spectroscopy is suggested and demonstrated for the diagnosis of Pseudomonas aeruginosa in urinary tract infection (UTI). The specific property of P. aeruginosa of metabolizing nicotinic acid to 6-hydroxynicotinic acid (6-OHNA) is exploited. The quantity of 6-OHNA produced correlates well with the viable bacterial count. Other common bacteria causing UTI such as Escherichia coli, Klebsiella pneumonia, Enterobacter aerogenes, Acinetobacter baumanii, Proteus mirabilis, Citrobacter frundii, Enterococcus faecalis, Streptococcus gp B and Staphylococcus aureus do not metabolize nicotinic acid under similar conditions. The method provides a single-step documentation of P. aeruginosa qualitatively as well as quantitatively. The NMR method is demonstrated on urine samples from 30 patients with UTI caused by P. aeruginosa. Copyright © 2005 John Wiley & Sons, Ltd.

Protonation of the tricyclic antidepressant drug trimipramine with maleic acid, methanesulfonic acid and hydrochloric acid was studied using 1H, 13C and 15N NMR spectroscopy at natural abundance. The effect of counter ions on the protonation was compared under identical conditions of solvent, concentration and temperature using homonuclear and heteronuclear one- and two-dimensional experiments. Differential protonation of the terminal tertiary amine nitrogen is determined from the indirect spin–spin couplings, chemical shifts, 13C relaxation data and variable-temperature experiments. In the maleate salt, only one of the acidic protons is involved in protonation, the other being associated with the anion moiety. 15N chemical shifts of the protonated nitrogens are nearly linearly related to the pKa of the constituent acid. Copyright © 2004 John Wiley & Sons, Ltd.

A simple method for quantification of conjugated bile acids in human bile using (1)H NMR spectroscopy is presented. Bile acids in human bile are essentially conjugated with either glycine or taurine. The amide NH resonances from the conjugated bile acids are invariably devoid of interfering signals in (1)H NMR spectra. Under physiologic conditions of human bile (pH approximately 7.0 to 7.7), amide signal intensities are attenuated due to the chemical exchange and hence quantitative estimation is precluded. In the present study, the quantity of total glycine and taurine conjugated bile acids could be obtained accurately by suppressing the amide exchange by reducing the pH slightly lower than physiologic value (6.0 +/- 0.5). Further, the quantity of glycine conjugated bile acids can be calculated accurately by subtracting the quantity of taurine conjugated bile acids from the total conjugated bile acids as determined from the present method.

Methyl-tri-n-decylphosphonium salts (1P10A, where the counterion A is NO 3 - or the hydrate of bromide, Br - .H 2 O) have been shown to exhibit unique liquid-crystalline properties as neat compounds and with high concentrations (up to 20 wt %) of a small organic molecule, acetonitrile. These results indicate dual thermotropic-lyotropic (i.e., amphotropic) behavior. Optical micrographs of salts with even small amounts of acetonitrile are oily streak patterns. The low-angle peaks in X-ray diffractograms characteristic of the lamellar spacings in the smectic A phases of the neat salts are broadened but do not change their positions appreciably as the concentration of added acetonitrile is increased. The liquid-crystalline phases of both salts become oriented in strong magnetic fields. As a result, NMR experiments with the nitrate salt exhibited only one type of orientation for acetonitrile at concentrations up to ca. 10 wt %. However, two types of orientations with opposite signs of the order parameter were detected in the Br - .H 2 O salt at < 1 wt % acetonitrile. The acetonitrile proton line width decreases by a factor of 2 between 0.7 and 13 wt % in the nitrate salt. The dual thermotropic-lyotropic behavior and relatively low order parameter of the solute suggest that these amphiphilic salts might be useful for structural studies using NMR spectroscopy.

The metabolite patterns obtained by ex vivo proton MR spectroscopy of fluid from different locations of hydatid cysts of sheep and humans (n = 16) and cysticercus cysts of swine and humans (n = 25) were compared with an objective of differentiating the two parasites on the basis of their metabolite pattern. The spectra from hydatid fluid differed from cysticercus cyst by the absence of creatine in the former. When the hydatid cyst was fertile, malate and/or fumarate was also observed, which was absent in cysticercus cyst. The most likely explanation for the presence of creatine only in the cysticercus fluid is its active diffusion from the surrounding host tissue along with a contribution from the musculature present in the bladder wall of the cyst.

The deuterium NMR spectra of molecules oriented in mixtures of nematic liquid crystalline phases for which the macroscopic diamagnetic susceptibility anisotropy (Δχ) is nearly zero reveal the dynamics of the director for different angles the spinning axis makes with the magnetic field and for different spinning speeds. It is observed that a switch over of the director orientation occurs as a function of the spinning speed and the angle the spinning axis makes with the magnetic field. The farther the angle between the spinning axis and the magnetic field from the magic angle, the higher the spinning speed required to effect such a switch over of the director orientation. The switch over takes place gradually as indicated by the appearance of the ‘powder pattern’ in the 2H NMR spectra.

The sound "OM" is believed to bring mental peace and calm. The cortical activation associated with listening to sound "OM" in contrast to similar non-meaningful sound (TOM) and listening to a meaningful Hindi word (AAM) has been investigated using functional magnetic resonance imaging (MRI). The behaviour interleaved gradient technique was employed in order to avoid interference of scanner noise. The results reveal that listening to "OM" sound in contrast to the meaningful Hindi word condition activates areas of bilateral cerebellum, left middle frontal gyrus (dorsolateral middle frontal/BA 9), right precuneus (BA 5) and right supramarginal gyrus (SMG). Listening to "OM" sound in contrast to "non-meaningful" sound condition leads to cortical activation in bilateral middle frontal (BA9), right middle temporal (BA37), right angular gyrus (BA 40), right SMG and right superior middle frontal gyrus (BA 8). The conjunction analysis reveals that the common neural regions activated in listening to "OM" sound during both conditions are middle frontal (left dorsolateral middle frontal cortex) and right SMG. The results correspond to the fact that listening to "OM" sound recruits neural systems implicated in emotional empathy.

The neat phases of a series of quaternary ammonium halides based on trioctadecylamine have been investigated by optical microscopy, differential scanning calorimetry, and H-2 NMR spectroscopy. Phase behaviour depends primarily on the structure of the fourth substituent on nitrogen and the thermal history of the samples. For instance, the iodide salts with methyl, ethyl, or propyl as the fourth substituent form enantiotropic nematic phases, while those with a proton or a longer alkyl substituent exhibit complex phase behaviour that does not include a liquid crystalline phase. Possible reasons are advanced for the unprecedented formation of nematic phases.

We examined cortical activations using functional magnetic resonance imaging (fMRI) technique in skilled native Hindi readers while they performed a ‘target-probe’ semantic judgment task on affirmative and negative sentences. Hindi, an Indo-Aryan language widely spoken in India, follows subject-object-verb (SOV) order canonically but allows free word order. The common cortical regions involved in affirmative and negative sentence conditions included bilateral inferior frontal gyrus (IFG), left parietal cortex (BA 7/40), left fusiform (BA 37), bilateral supplementary motor area (SMA) (BA 6), bilateral middle temporal gyrus (BA 21), and bilateral occipital area (BA 17/18). While no distinct region was activated for affirmative sentences, we observed activations in the region of bilateral anterior temporal pole for negative sentence. The behavioral results showed no significant mean difference for reaction times (RT) and accuracy measures between affirmative and negative sentences. However, the imaging results suggest the recruitment of anterior temporal pole in processing of negative sentences. Region of interest (ROI) analysis for selected regions showed higher signal intensity for negative sentences possibly indicating the associated inherent difficulty level of processing, especially when integrating information related to negations.

To address the shortcomings of urine culture for the rapid identification of urinary tract infection (UTI), we applied (1)H-nuclear magnetic resonance (NMR) spectroscopy as a surrogate method for fast screening of microorganisms. Study includes 682 urine samples from suspected UTI patients, 50 healthy volunteers, and commercially available standard strains of gram negative bacilli (GNB) (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Enterobacter, Acinetobacter, Proteus mirabilis, Citrobacter frundii) and gram positive cocci (GPC) (Enterococcus faecalis, Streptococcus group B, Staphylococcus saprophyticus). Acetate, lactate, ethanol, succinate, creatinine, trimethylamine (TMA), citrate, trimethylamin-N-oxide, glycine, urea, and hippurate were measured by (1)H NMR spectroscopy. All urine specimens were evaluated with culture method. Multivariate discriminant function analysis (DFA) reveals that acetate, lactate, succinate, and formate were able to differentiate, with high accuracy (99.5%), healthy controls from UTI patients. This statistical analysis was also able to classify GNB to GPC infected urine samples with high accuracy (96%). This technique appears to be a promising, rapid, and noninvasive approach to probing GNB and GPC infected urine specimens with its distinguishing metabolic profile. The determination of infection will be very important for rapidly and efficiently measuring the efficacy of a tailored treatment, leading to prompt and appropriate care of UTI patients.

Proanthocyanidin is commonly used for inhibiting urinary tract infection (UTI) of sensitive strains of Escherichia coli. The aim of this study was to investigate the effect of proanthocyanidin on adherence of uropathogenic multi-drug resistant E. coli to uroepithelial cells, which has not yet been investigated so far. Extracts of the purified proanthocyanidin were prepared from dried cranberry juice. Purity and structural assignment of proanthocyanidin was assessed using high performance liquid chromatography and (13)C nuclear magnetic resonance spectroscopy, respectively. Subsequently, its affect on multi-drug resistant bacteria as well as quantification of anti-adherence bioactivity on human vaginal and bladder epithelial cells was appraised. Inhibition of adherence to an extent of about 70% with multi-drug resistant E. coli strains was observed on uroepithelial cell. The anti-adherence bioactivity of the proanthocyanidin was detected at concentrations of 10-50 µg/ml with significant bacteriuria. Probable proanthocyanidin through A-type linkages either combines to P-fimbriae of bacterial cells or modifies the structural entity of P-fimbriae and inhibits bacterial adherence to uroepithelial cells. The proanthocyanidin exhibited anti-adherence property with multi-drug resistant strains of uropathogenic P-fimbriated E. coli with in vitro study. Hence proanthocyanidin may be considered as an inhibitory agent for multi-drug resistant strains of E. coli adherence to uroepithelial cells.

Profiling of metabolites is a rapidly expanding area of research for resolving metabolic pathways. Metabolic fingerprinting in medicinally important plants is critical to establishing the quality of herbal medicines. In the present study, metabolic profiling of crude extracts of leaf and root of Withania somnifera (Ashwagandha), an important medicinal plant of Indian system of medicine (ISM) was carried out using NMR and chromatographic (HPLC and GC-MS) techniques. A total of 62 major and minor primary and secondary metabolites from leaves and 48 from roots were unambiguously identified. Twenty-nine of these were common to the two tissues. These included fatty acids, organic acids, amino acids, sugars and sterol based compounds. Eleven bioactive sterol-lactone molecules were also identified. Twenty-seven of the identified metabolites were quantified. Highly significant qualitative and quantitative differences were noticed between the leaf and root tissues, particularly with respect to the secondary metabolites.

Amyotrophic lateral sclerosis (ALS), an invariably fatal neurological disorder shows complicated pathogenesis that poses challenges with respect to diagnosis as well as monitoring of disease progression.We investigated metabolite profiles in the serum of 30 patients with ALS, 10 patients of Hirayama disease, which served as a neurological disease control and 25 healthy controls by using (1) H NMR spectroscopy.Compared to healthy controls, the ALS patients had higher quantities of glutamate (P0.001), beta-hydroxybutyrate (P0.001), acetate (P0.01), acetone (P0.05), and formate (P0.001), and lower concentrations of glutamine (P0.02), histidine (P0.001) and N-acetyl derivatives. On the other hand, Hirayama disease patients had significantly higher median concentrations of pyruvate (P0.05), glutamate (P0.001), formate (P0.05) and lower median concentrations of N-acetyl derivatives. Furthermore, we also found that serum glutamate showed a positive correlation (P0.001, r=0.6487) whereas, histidine showed a negative correlation (P0.001, r=-0.5641) with the duration of the disease in ALS.Such (1) H NMR study of serum may reveal abnormal metabolite patterns, which could have the potential to serve as surrogate markers for monitoring ALS disease progression.

Patients with extrahepatic biliary obstruction present with impairment of the normal bile flow, with jaundice and cholangitis as common complications. 1H and 31P NMR quantitative analysis of bile specimens from patients with extrahepatic biliary obstruction (n = 80) (with/without jaundice and cholangitis separately and together) was carried out for the chief biliary constituents to determine the relationship between biliary constituents and jaundice (serum bilirubin concentration ≥1.0 mg/dL) and cholangitis (total leucocyte count >11 000 cells/mm3 and/or fever >38.5°C with/without bile culture positivity). Compared with controls (patients without jaundice and cholangitis), median indices of the chief biliary constituents (total bile acids, cholesterol, phosphatidylcholine and inorganic phosphate) were significantly suppressed in patients with cholangitis and/or jaundice. Quantities of total bile acids, cholesterol and phosphatidylcholine correlated negatively with the quantity of bilirubin and with cholangitis, i.e. total leucocyte count. Suppression of biliary constituents correlated significantly with the severity of jaundice and cholangitis. The decrease in biliary constituents in the presence of jaundice and cholangitis is possibly the result of downregulation of the function of transporters located at the canalicular side of hepatocytes, leading to their suppressed indices in bile. This information may have implications in the examination of bile for clinical studies. Copyright © 2008 John Wiley & Sons, Ltd.

Tri- n-decylmethylphosphonium chloride and bromide ( 1P10X) salts are not liquid crystalline. However, mesophases are induced by adding very small amounts of an alcohol or water. The temperature ranges of the induced smectic A 2 (SmA 2) liquid-crystalline phases can be very broad and the onset temperatures can be below room temperature depending upon the concentration of the alcohol or water and the structure of the alcohol. At least one molar equivalent of hydroxyl groups is necessary to convert the 1P10X completely into a liquid crystal. Strong association between the hydroxyl groups of an alcohol or water and the head groups of the 1P10X is indicated by spectroscopic, diffraction, and thermochemical data. Unlike many other smectic phases, those of the 1P10X/alcohol complexes are easily aligned in strong magnetic fields and the order parameters of selectively deuterated alcohols as measured by (2)H NMR spectroscopy, approximately 10 (-2), are much lower than the values found when the host is a commonly employed thermotropic liquid crystal. The dependence of the specific values of the order parameters on temperature, the nature of the halide anion, and the structure and concentration of the alcohol are reported. In sum, a detailed picture is presented to explain how and why an alcohol or water induces liquid crystallinity in the 1P10X salts. The data also provide a blueprint for designing media with even lower order parameters that can be hosts to determine the conformations and shapes of guest molecules.

The toxic effects of Al3+ have been studied in 90-days AlCl3 orally treated male albino rats (n = 7) using 1H NMR spectroscopy-based metabolic profile of rat serum and urine, serum enzyme tests, behavioral impairment, and histopathology of kidney and liver. Metabolic profile of 90-days Al3+-treated rat sera showed significantly elevated levels of alanine, glutamine, β-hydroxy-butyrate, and acetoacetate and significantly decreased level of acetone when compared with that of control rats. However, metabolic profile of 90-days Al3+-treated rat urine showed significantly decreased levels of citrate, creatinine, allantoin, trans-aconitate, and succinate and significantly increased level of acetate when compared to control rats. The overall perturbations observed in the metabolic profile of serum and urine demonstrate the impairment in the tricarboxylic acid cycle, liver and kidney metabolism, which was further reinstated by clinical chemistry and histopathological observations. Moreover, “in vivo” behavioral impairment has also been observed as the indication of aluminum neurotoxicity. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:119–127, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20219

Seed development in Jatropha curcas L was studied with respect to phenology, oil content, lipid profile and concentration of sterols. Seeds were collected at various stages of development starting from one week after fertilization and in an interval of five days thereafter till maturity. These were classified as stage I to stage VII. Moisture content of the seeds ranged from 8.8 to 90.3%; the lowest in mature seeds in stage VII and highest in stage 1. The seed area increased as the seed grew from stage I to stage VI (0.2-10.2 mm(2) per seed), however, the seed area shrunk at stage VII. Increase in seed area corresponded to increase in fresh weight of the seeds. H-1 NMR spectroscopy of hexane extracts made at different stages of seed development revealed the presence of free fatty acids (FFA), methyl esters of fatty acids (FAME) and triglycerol esters (TAG), along with small quantity of sterols. The young seeds synthesized predominantly polar lipids. Lipid synthesis was noticed nearly three weeks after fertilization. From the fourth week the seeds actively synthesized TAG. Stage Ill is a turning point in seed development since at this stage, the concentration of sterols decreased to negligible, there was very little FAME formation, accumulation of TAG increased substantially, and there was a Sudden decrease in FFA concentration. The findings can be helpful in understanding the biosynthesis and in efforts to improve biosynthesis of TAG and reduce FFA content in the mature seeds. (C) 2008 Elsevier Ltd. All rights reserved.

1H and 13C NMR spectra of intact human bile were assigned using one-dimensional (1H and 13C) and two-dimensional (1H-1H and 1H-13C) experiments. Individual conjugated bile acids--glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid--were identified. The bile acids were quantified accurately and individually in a single step by using distinct and characteristic amide signals. Making use of 13C NMR, the study also suggests a way to analyze unconjugated bile acids separately, if present. Chemical shift assignments and rapid single-step analysis of individual conjugated bile acids from intact bile presented herein may have immense utility in the study of bile acid metabolism and deeper understanding of hepatobiliary diseases.

Human gallbladder bile dissolved in dimethyl-sulfoxide provides sharp and resolved signals for major bile components in 1H NMR spectra. Characteristic well-resolved marker signals that invariably appear in 1H NMR spectra of bile were identified for cholesterol (H18 methyl signal at 0.643 ppm), lipids (glycerol CH signal at 5.064 ppm), total bile acids (H18 signals in the range 0.520–0.626 ppm), total glycine conjugated bile acids (NH signal at 6.958 ppm), total taurine conjugated bile acids (NH signal at 7.646 ppm), and urea (NH2 signal near 5.48 ppm), which enabled their rapid and accurate analysis. Excellent linearity and precision of quantitative analysis was observed for all the identified bile components (R2>0.99 for all). The method was demonstrated on gallbladder bile from 19 patients with gallbladder diseases. Urea in bile was identified by NMR for the first time and its quantitative analysis, along with several other bile components, is presented. The majority of the bile components could be analyzed in a single step. Accurate and rapid quantification of several bile components noninvasively by using the method presented herein may have far-reaching implications in the study of bile acid metabolism and pathophysiology of various hepatobiliary and gastrointestinal diseases.

Biochemicals in the upper-gut aspirate in 31 patients with malabsorption syndrome (MAS) with and without small intestinal bacterial overgrowth (SIBO), and 10 disease-free controls were analyzed using high-resolution (1)H-NMR spectroscopy, and were correlated with the degree of SIBO and severity of MAS. Compared to controls, the patients had higher quantities (micromol/L: median [range]) of total bile acids/cholesterol (2000 [0-12000] vs. 300 [0-600]), lactate (700 [0-5200] vs. nil [0-30]), acetate (200 [0-6500] vs. 20 [0-200]), and formate (80 [0-900] vs. nil [0-50]) (P < 0.01, Mann-Whitney U-test). However, amino acids and glucose were comparable in both. Quantities (micromol/L: median [range]) of acetate (1330 [220-6500] vs. 100 [0-1430]), lactate (1430 [670-3300] vs. 300 [0-5200]), formate (360 [0-600] vs. 25 [0-800]), and unconjugated bile acids (500 [40-600] vs. 10 [0-300]) were higher in MAS patients with SIBO than those without SIBO (P < 0.01, Mann-Whitney U-test, for all). In patients with MAS the quantity of acetate positively correlated with the degree of SIBO, and unconjugated bile acids correlated with the degree of steatorrhoea (Spearman's rank correlation coefficient, two-tailed, P < 0.05: 0.46 and 0.52, respectively). This study demonstrates the bacterial production of metabolites and deconjugation of bile acids in patients with MAS.

The (1)H NMR spectroscopic method is suggested and its utility is demonstrated for the diagnosis of Klebsiella pneumoniae (K. pneumoniae) in urinary tract infection (UTI). K. pneumoniae have the specific property of metabolizing glycerol to 1,3-propanediol (1,3-PD), acetate, ethanol and succinate. The quantity of 1,3-PD produced correlates well with the viable bacterial count. Other common bacteria causing UTI (except for Citrobacter frundii), such as Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Enterobacter aerogenes, Acinetobacter baumanii, Proteus mirabilis, Enterococcus faecalis, Streptococcus gp B and Staphylococcus aureus do not metabolize glycerol under similar conditions. Citrobacter frundii (C. frundii) also gives the same NMR results but is easily differentiated as being motile on direct microscopic examination of urine and it is not common nosocomial infectious agent in urinary tract infection. The method provides a single-step documentation of K. pneumoniae (and C. frundii) qualitatively as well as quantitatively. Out of the total 614 subjects considered, clinical diagnosis of UTI was obtained in 516 cases (84%). The NMR-based screening had a sensitivity of 90%, a specificity of 100% and a false negativity of 10% relative to the conventional quantitative culture method. In the present authors' experience, the results of NMR spectroscopy based screening show a very good correlation with the diagnosis of urinary tract infected patients.

A protonation and dynamic structural study of doxylamine succinate, a 1:1 salt of succinic acid with dimethyl-[2-(1-phenyl-1-pyridin-2-yl-ethoxy)ethyl]amine, in solution using one- and two-dimensional 1H and 13C NMR experiments at variable temperature and concentration is presented. The two acidic protons of the salt doxylamine succinate are in 'intermediate' exchange at room temperature, as evidenced by the appearance of a broad signal. This signal evolves into two distinct signals below about -30 degrees C. A two-dimensional 1H-1H double quantum filtered correlation experiment carried out at -55 degrees C shows protonation of one of the acidic protons to the dimethylamine nitrogen. A two-dimensional rotating frame 1H-1H NOE experiment at the same temperature reveals that the other proton remains with the succinate moiety. Comparison of the 1H and 13C chemical shifts and the 13C T1 relaxation times of the salt with those of the free base further substantiate the findings.

Despite its well-documented limitations, colorimetry has been commonly used for the d-xylose test in the diagnosis of malabsorption syndrome (MAS). With a possibility of overcoming its limitations, the use of 1H NMR spectroscopy for D-xylose test is explored herein. Urine samples from 35 adults with suspected MAS were obtained before and after oral ingestion of D-xylose. The diagnosis of MAS was based on fecal fat (72 h excretion using Van de Kamer's technique, normal

High-resolution 1H-NMR spectroscopy of serum and urine samples of an 11-year-old male living related orthotopic liver transplant recipient is reported. Serum glutamine increased to abnormal levels along with simultaneous abnormal excretion of urinary glutamine post-transplantation. High levels of glutamine in both blood and urine and concomitant reduced urea levels in urine were found to be evidence of impairment in urea cycle and compatible with persistently abnormal graft function. Thus glutamine levels in serum and urine, and urea in the urine as observed by 1H-NMR spectroscopy highlight their important roles in monitoring liver graft function; increased glutamine levels lead to brain damage, if untreated. Copyright © 2003 John Wiley & Sons, Ltd.

The 1963 observation of Englert and Saupe [1] that the 1HNMR spectrum of benzene in a nematic liquid crystalline phase has a complex appearance compared to a single line in an isotropic medium (Fig. 7.1) has led to the discovery of a new method for the determination of molecular structure. It provides the only direct method for the precise determination of molecular geometries in the liquid phase and is the latest addition to the earlier existing list of methods such as X-ray, neutron and electron diffractions and microwave spectroscopy.

The products of lipid mobilization in groundnut (Arachis hypogaea L.) seeds as a function of time immediately after imbibition are monitored by (13)C NMR. Different parts of the embryonic axis, namely, the radicle, hypocotyl, and plumule, exhibit characteristic time dependent (13)C NMR spectra observed at 24-h intervals after imbibition. The various stages in the transformation of storage lipids present in different parts of the embryonic axis are clearly demonstrated. The transformation of storage lipids is completed first in the radicle followed by the hypocotyl and finally the plumule. A mechanism of the transformation of the storage lipids is discussed.