Proton Magnetic Resonance Spectroscopy Study Research Articles

Peripheral inflammation is associated with alterations in brain biochemistry and mood: evidence from in vivo proton magnetic resonance spectroscopy study

Abstract Tumor necrosis factor (TNF)-α is a protein implicated in the prognosis of psoriatic arthritis (PsA), an autoimmune disease associated with episodes of clinical depression (CD). CD has been linked to abnormalities in the forebrain and subcortical structures, which can be probed noninvasively using proton magnetic resonance spectroscopy (1H-MRS). Thus, this 1H-MRS study assessed biochemical differences between healthy subjects and PsA patients in the frontal and bilateral hippocampal brain regions. Biochemical and mood responses in the anterior cingulate cortex and bilateral hippocampi following the administration of anti-TNF-α medication to the PsA patients were also assessed. Fifteen volunteers in each of the PsA and control groups participated in the study. Patients underwent MRS examination before and after 6–8 weeks of anti-TNF-α medication. Mood was assessed at baseline and after medication using the Beck’s Depression Inventory (BDI). Psychiatric symptoms were ruled out in all volunteers using the 12-item General Health Questionnaire. MRS studies were conducted using the PRESS sequence at 3 T. Spectral and statistical analyses were conducted using the LC Model and Minitab software, respectively. Metabolite levels were expressed as ratios, relative to the creatine peak. The PsA patients showed higher left hippocampal baseline Choline/Creatine ratio than controls (p = 0.014). After medication, decrease in frontal brain Choline/Creatine ratio was associated with decrease in BDI scores (r = 0.628; p = 0.025), while frontal brain NAA/Creatine ratio was significantly lower in the PsA patients compared to the controls (p = 0.023). No other significant differences were found in all comparisons, including metabolite ratios between the left and right hippocampi. The results of this study provide some evidence for biochemical alterations in the mood regulating segments of the brain, which has consequences for mood states of the affected patients.

Kinetic and Spectroscopic Studies of Methyl Ester Promoted Methanol Dehydration to Dimethyl Ether on ZSM-5 Zeolite

Methyl carboxylate esters have been shown to be potent promoters of low-temperature methanol dehydration to dimethyl ether (DME) using various zeolite catalysts. In the present work, catalytic kinetic studies, in-situ Fourier-transform infrared spectroscopy (FT-IR) and solid-state nuclear magnetic resonance spectroscopy (NMR) techniques were used to elucidate the promotional mechanism of methyl carboxylate esters on methanol dehydration to DME, using the medium pore zeolite H-ZSM-5 (MFI) as the catalyst. Kinetic studies were performed using the very potent methyl n-hexanoate promoter. The DME yield was dependent on both the methanol and methyl n-hexanoate partial pressures across the temperature ranges used in this study (110 to 130 °C). This is consistent with the promoted reaction being a bimolecular reaction between methanol and ester species adsorbed at the catalyst active sites, via an SN2 type reaction, as previously postulated. The in-situ FT-IR studies reveal that the Brønsted acid (BA) sites on H-ZSM-5 were very rapidly titrated by ester carbonyl group adsorption and bonded more strongly with esters than with methanol. Upon methanol addition, an even lower DME formation temperature (30 °C) was observed with methyl n-hexanoate pretreated H-ZSM-5 samples in the in-situ NMR studies, further confirming the strong promotion of this methyl ester on methanol dehydration to DME. The adsorption and reactivity of different methyl esters on H-ZSM-5 indicates that while methyl formate more easily dissociates into a surface methoxy species, [Si(OMe)Al], and carboxylic acid, it is a less potent promoter than alkyl-chain-containing methyl esters in methanol dehydration to DME, which in turn did not show this dissociative behavior in the low-temperature NMR studies. This indicates that methyl alkyl carboxylates do not need to be dissociated to a surface methoxy species to promote the methanol dehydration reaction and that a bimolecular associative mechanism plays an important role in promoting DME formation.

An insight into lithium-ion transport in germanium-doped lithium titanate anode through NMR spectroscopy and post-carbonization for anode applications in lithium-ion battery

Adapting toward lithium titanate as a negative electrode for lithium-ion batteries led to the safest and long-lasting battery technology, especially for electric vehicle applications. However, the poor conductivity and lithium-ion diffusion of lithium titanate have to be addressed for widespread usage in next-generation E-mobility. The lithium-ion motion inside lithium titanate and germanium-doped lithium titanate was investigated through pulsed-field gradient nuclear magnetic resonance spectroscopy and temperature-dependent ionic conductivity studies. The superior charge carrier mobility of germanium enhanced the lithium-ion diffusion in lithium titanate significantly to 1.48 × 10−8 cm2 s−1 in Li4Ge0.1Ti4.9O12 at 500 °C. While germanium improves the ionic diffusion, an ex situ carbon coating was adapted over the sample for electronic conductivity enhancement. Samples with two different carbon contents (5 and 10 wt. %) were examined for electrochemical analysis. Significant improvements in battery performance were observed on carbon-coated germanium-doped lithium titanate. The carbon-coated sample gave superior initial performance (191 and 178 mAh g−1 for 10 and 5 wt. % carbon at 0.1C) than the pristine lithium titanate and preserved the exceptional capacity retention over a thousand cycles at 1C rate.

Curcumin-Loaded PnBA-b-POEGA Nanoformulations: A Study of Drug-Polymer Interactions and Release Behavior.

The current study focuses on the development of innovative and highly-stable curcumin (CUR)-based therapeutics by encapsulating CUR in biocompatible poly(n-butyl acrylate)-block-poly(oligo(ethylene glycol) methyl ether acrylate) (PnBA-b-POEGA) micelles. State-of-the-art methods were used to investigate the encapsulation of CUR in PnBA-b-POEGA micelles and the potential of ultrasound to enhance the release of encapsulated CUR. Dynamic light scattering (DLS), attenuated total reflection Fourier transform infrared (ATR-FTIR), and ultraviolet-visible (UV-Vis) spectroscopies confirmed the successful encapsulation of CUR within the hydrophobic domains of the copolymers, resulting in the formation of distinct and robust drug/polymer nanostructures. The exceptional stability of the CUR-loaded PnBA-b-POEGA nanocarriers over a period of 210 days was also demonstrated by proton nuclear magnetic resonance (1H-NMR) spectroscopy studies. A comprehensive 2D NMR characterization of the CUR-loaded nanocarriers authenticated the presence of CUR within the micelles, and unveiled the intricate nature of the drug-polymer intermolecular interactions. The UV-Vis results also indicated high encapsulation efficiency values for the CUR-loaded nanocarriers and revealed a significant influence of ultrasound on the release profile of CUR. The present research provides new understanding of the encapsulation and release mechanisms of CUR within biocompatible diblock copolymers and has significant implications for the advancement of safe and effective CUR-based therapeutics.

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan’s unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = −0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = −0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = −0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = −0.02, p < 0.001) and frontal white matter Glx (z = −0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.

LC-HRMS and NMR studies for characterization of forced degradation impurities of ponatinib, a tyrosine kinase inhibitor, insights into in-silico degradation and toxicity profiles

The degradation profile of ponatinib was established during the present study by exposing it to various stress conditions. In-silico degradation pattern of ponatinib was outlined by using Zeneth software. Five degradation impurities were formed during the stress testing of ponatinib. High performance liquid chromatographic method was developed to separate these degradation impurities which includes ammonium acetate of pH 4.75 (A) and methanol (B) as mobile phase in gradient elution mode and Waters Reliant C18 (4.6 × 250 mm, 5 µm) column as stationary phase. Optimised flow rate, injection volume and detection wavelength of the HPLC method were 1.0 mL/min, 10 µL and 254 nm, respectively. Chemical structures of degradation impurities were proposed by high resolution mass spectrometry further, major degradation products were isolated, enriched and investigated thoroughly with the aid of nuclear magnetic resonance spectroscopy studies. The degradation impurities were identified as 4-aminophthalaldehyde (DP 1), 4-((4-methylpiperazin-1-yl)methyl)− 3-(trifluoromethyl) benzenamine (DP 2), 3-(2-(imidazo[1,2-b]pyridazin-3-yl)acetyl)− 4-methylbenzoic acid (DP 3), 3-(2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl)− 4-methylbenzoic acid (DP 4) and N-oxide impurity (DP 5) which are new and were not reported in the literature till date. Additionally, toxicity and mutagenicity profiles of ponatinib and its degradation impurities were predicted in-silico by using DEREK and SARAH software. This whole study gives meaningful insights about chemical stability of ponatinib which is useful in its drug development lifecycle.

What Changes Occur in the Brain of Veteran? A Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy Study

The aims of this study were to assess the common anomalies in the MRI examinations of the heads of soldiers as well as to compare the relative concentration of magnetic resonance spectroscopy (MRS) metabolites in the brains of soldiers with those of healthy age-matched controls. Overall, 54 professional male soldiers were included in the study group and 46 healthy, age-matched males were in the control group. The relative values of N-acetylaspartate (NAA), choline (Cho), and myoinositol (mI) to creatine (Cr) were assessed. The mean relative concentrations of metabolites were compared between the study and the control group, separately for the frontal and occipital lobes, as well as between the right and left hemispheres within the study group only. The most frequent findings in the head MRI of the soldiers were: asymmetric lateral ventricles and dilated perivascular spaces, enlargement of the subarachnoid spaces, and the presence of cavum septum pellucidum and cavum vergae; the high frequency of sinus disease should also be noted. In the frontal lobes, the mI/Cr ratio was significantly higher (p = 0.005), while the NAA/Cr ratio was lower (p = 0.001), in the group of soldiers (vs. the study group). In the occipital lobes, the NAA/Cr ratio was significantly lower (p = 0.005) in the military personnel and there was a tendency to a higher mI/Cr ratio in the soldiers’ occipital lobes (p = 0.056) (vs. the study group). Comparing the metabolites between the left and right hemispheres in soldiers preferring a right shooting position, a significantly higher mI/Cr (p &lt; 0.001) ratio was observed in the right frontal lobe (vs. the left) and a markedly lower NAA/Cr (p = 0.003) in the right occipital lobe (vs. the left). These changes are associated with astrogliosis and neuronal loss, presumably secondary to repetitive mild traumatic brain injury.

Fronto-Cerebellar Neurometabolite Alterations After Methylphenidate in Children and Adolescents With ADHD: A Proton Magnetic Resonance Spectroscopy Study

Objective: The fronto-cerebellar circuit is involved in ADHD pathophysiology. Methylphenidate, as a first-line medication for ADHD, affects different brain regions, however, its effect on the fronto-cerebellar circuit is not investigated sufficiently. We aimed to investigate the effect of 8-week treatment with methylphenidate on neurometabolite ratios in the fronto-cerebellar circuit in ADHD participants using magnetic resonance spectroscopy (MRS). Methods: Fifteen drug-naïve ADHD children and adolescents were enrolled in the present study. Two single-voxel MR spectra were acquired from the right dorsolateral prefrontal cortex (DLPFC) and left Crus 1, before and after the medication. Also, neuropsychological and behavioral assessments were administered. Results: After medication, the glutamate/creatine in the DLPFC and the choline/creatine in the Crus 1 decreased in the ADHD participants. Conclusion: These findings propose that methylphenidate-induced metabolite changes in the fronto-cerebellar circuit could be associated with improvement in cognitive/behavioral characteristics in ADHD. Also, results highlighted cerebellar engagement in ADHD pathophysiology.

A New Non-linear Stilbazolium Derivative Crystal of 4-[2-(3 Methoxy-phenyl)-vinyl]-1-methyl-pyridinium+ Iodide− (MMPI): Analysis of Its Structural, Surface, Optical and NLO Properties

New organic stilbazolium family of 4-[2-(3 methoxy-phenyl)-vinyl]-1-methyl-pyridinium+ iodide− (MMPI) was successfully synthesized using the condensation reaction method. The recrystallization process was carried out to improve the purity of the synthesized material, and MMPI and grown into a single crystal by the solvent evaporation method. The solubility of the (MMPI) material was taken at different temperatures with a mixture of solvent Methanol: Acetonitrile (1:1). The grown MMPI crystal structure and cell parameters were solved via single crystal X-ray diffraction analysis. The structural formation of the title material was also confirmed by Nuclear Magnetic Resonance spectroscopic (NMR) studies. The experimental vibrational bands in the synthesized material have been assigned by Fourier Transform Infrared (FT-IR) spectrum analysis. From the optical analysis, the grown crystal’s lower cut-off wavelength, transmittance range, and optical band gap were calculated. Chemical etching analysis was carried out on the grown crystal surface (MMPI) to study the surface property of the grown MMPI crystal. Along with etching, atomic force microscope (AFM) and scanning electron microscope (SEM) were also used to analyses the grown MMPI crystal surface. Hirshfeld surface analysis was used to analyses the intermolecular interactions. HOMO and LUMO energies were calculated theoretically using the Gaussian View 6 programmer. The chemical activity was evaluated via the molecular electrostatic potential using the density functional theory (DFT) method. The third-order nonlinear optical parameters of the title crystal were evaluated at He-Ne laser (632.8 nm) source with the single beam Z-scan technique. In addition, it shows significant reverse saturable absorption and self-defocusing.

Changes in gamma-aminobutyric acid and glutamate/glutamine levels in the right thalamus of patients with episodic and chronic migraine: A proton magnetic resonance spectroscopy study.

To explore gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine. Migraine affects approximately 1 billion people worldwide, with 2.5%-3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. In this cross-sectional study, patients with EM and CM were recruited. Mescher-Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs). A total of 26 patients (EM, n= 11; CM, n= 15) and 16 age- and sex-matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p= 0.026; mean difference [MD]=-0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p= 0.023, MD < -0.1, and p= 0.034, MD < -0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1) (p= 0.024; MD=-0.1). The area under the curve for GABA+/Water levels in differentiating patients with CM from HCs was 0.83 (95% confidence interval 0.68, 0.98; p= 0.004). Correlation analyses within the migraine group revealed no significant correlation between metabolite concentration levels and headache characteristics after Bonferroni correction. Reduced GABA+/Water levels and imbalance of excitation/inhibition in the right thalamus may contribute to migraine chronification.

Glutathione alterations in depression: a meta-analysis and systematic review of proton magnetic resonance spectroscopy studies

Glutathione alterations in depression: a meta-analysis and systematic review of proton magnetic resonance spectroscopy studies

Normal Appearing White Matter N-Acetylaspartate Changes Impact on Fatigue in Multiple Sclerosis

Background: Fatigue is one of the most frequent complaints presented by multiple sclerosis patients. Fatigue may be multifactorial. Proton magnetic resonance spectroscopy studies have shown significant reductions in N-acetylaspartate/creatine ratios in multiple brain regions among fatigued multiple sclerosis patients in comparison to non-fatigued multiple sclerosis patients, suggesting axonal loss as a contributing factor. Females are twice as likely to develop the disease. Aim: To evaluate gender variability in fatigue scores in relapsing-remitting multiple sclerosis patients. To explore potential gender differences in metabolite profiles of normal appearing white matter. To correlate metabolite changes distribution with fatigue severity and to evaluate the gender impact. Methods: We enrolled 50 relapsing-remitting multiple sclerosis patients on disease modifying treatment and 28 healthy controls. All participants underwent proton magnetic resonance spectroscopy of normal appearing white matter corresponding regions and fatigue severity evaluation. Results: We found higher fatigue scores in the multiple sclerosis group, due to greater severity in female subjects. We found a significant decrease of N-acetylaspartate/creatine ratio with increase in N-acetylaspartate, choline, and creatine levels in multiple sclerosis subjects. N-acetylaspartate and choline levels were significantly higher in the multiple sclerosis males. Female multiple sclerosis patients presented with lower N-acetylaspartate levels than healthy controls and greater increases in Fatigue Severity Scale score. Regression analysis revealed metabolite specific relationships between fatigue against metabolite variables. Conclusion: Proton magnetic resonance spectroscopy registered differences in metabolite profiles in normal appearing white matter male and female multiple sclerosis subjects. We might presume gender dependent specifiers in metabolite profiles in relapsing- remitting multiple sclerosis. They impact fatigue severity. N- acetyaspartate might be crucial contributor in central fatigue in multiple sclerosis. Bioenergetic role of N-acetylaspartate needs further collaborative research on genetics and electrical properties of neurons to reveal the underlying mechanism of fatigue and conductivity deterioration.

Effect of modulator ligands on the growth of Co2(dobdc) nanorods.

Control over the size, shape, uniformity, and external surface chemistry of metal-organic framework nanocrystals is important for a wide range of applications. Here, we investigate how monotopic modulators that mimic the coordination mode of native bridging ligands affect the growth of anisotropic Co2(dobdc) (dobdc4- = 2,5-dihydroxy-1,4-benzenedicarboxylic acid) nanorods. Through a combination of transmission electron microscopy (TEM) and nuclear magnetic resonance spectroscopy (NMR) studies, nanorod diameter was found to be strongly correlated to the acidity of the modulator and to the degree of modulator incorporation into the nanorod structure. Notably, highly acidic modulators allowed for the preparation of sub-10 nm nanorods, a previously elusive size regime for the M2(dobdc) family. More broadly, this study provides new insights into the mechanism of modulated growth of metal-organic framework nanoparticles.

Comprehensive study on degradation profile of firocoxib and structural elucidation of its key degradation products

Firocoxib is widely used in veterinary medicine as a non-steroidal analgesic and anti-inflammatory drug substance. Herein, a comprehensive study on the degradation profile of firocoxib was performed through force degradation studies to understand its degradation profile and characterize its major degradation products (DPs). Firocoxib drug substance was subjected to acidic, alkaline, oxidation (H2O2, KMnO4, and K2Cr2O7), thermal (solid and solution state), and photolytic (solid and solution state) stress degradation, as recommended in the ICH guidelines. Firocoxib and its major DPs were adequately separated by investigational HPLC method, which utilized a HALO C18 (100 × 2.1 mm, 2.0 µm) column. Mobile phase-A for the HPLC method is composed of 0.1% formic acid in water and mobile phase-B acetonitrile. A total of six major DPs were observed for firocoxib drug substance under these stress degradation conditions. Structural elucidation of the DPs performed using liquid chromatography-high resolution mass spectrometry and comparison of their fragmentation profile with that of the parent compound. For further structural confirmation of two major DPs, DP-2 and DP-6 were isolated and purified from the stressed samples using a preparative HPLC and analyzed by comprehensive nuclear magnetic resonance (NMR) spectroscopy studies. Most probable mechanistic pathways for the formation of DPs of firocoxib under various stress degradation conditions were postulated to understand its degradation profile. Based on the results from forced degradation, firocoxib was found to be quite stable under basic and thermal conditions, and somewhat unstable under acidic, oxidative, and photolytic conditions. The results of this study should facilitate quality monitoring and establish a stability profile of firocoxib drug substance and drug products. These results may also assist in the design and development of new formulations made with firocoxib drug substance with desired shelf life.

Mechanistic Insights into IscU Conformation Regulation for Fe-S Cluster Biogenesis Revealed by Variable Temperature Electrospray Ionization Native Ion Mobility Mass Spectrometry.

Iron-sulfur (Fe-S) cluster (ISC) cofactors are required for the function of many critical cellular processes. In the ISC Fe-S cluster biosynthetic pathway, IscU assembles Fe-S cluster intermediates from iron, electrons, and inorganic sulfur, which is provided by the cysteine desulfurase enzyme IscS. IscU also binds to Zn, which mimics and competes for binding with the Fe-S cluster. Crystallographic and nuclear magnetic resonance spectroscopic studies reveal that IscU is a metamorphic protein that exists in multiple conformational states, which include at least a structured form and a disordered form. The structured form of IscU is favored by metal binding and is stable in a narrow temperature range, undergoing both cold and hot denaturation. Interestingly, the form of IscU that binds IscS and functions in Fe-S cluster assembly remains controversial. Here, results from variable temperature electrospray ionization (vT-ESI) native ion mobility mass spectrometry (nIM-MS) establish that IscU exists in structured, intermediate, and disordered forms that rearrange to more extended conformations at higher temperatures. A comparison of Zn-IscU and apo-IscU reveals that Zn(II) binding attenuates the cold/heat denaturation of IscU, promotes refolding of IscU, favors the structured and intermediate conformations, and inhibits the disordered high charge states. Overall, these findings provide a structural rationalization for the role of Zn(II) in stabilizing IscU conformations and IscS in altering the IscU active site to prepare for Zn(II) release and cluster synthesis. This work highlights how vT-ESI-nIM-MS can be applied as a powerful tool in mechanistic enzymology by providing details of relationships among temperature, protein conformations, and ligand/protein binding.

Glutamatergic Neurometabolite Levels in Bipolar Disorder: A Systematic Review and Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies

BackgroundThe glutamatergic system is thought to play an important role in the pathophysiology of bipolar disorder (BD). While there has been an increase in proton magnetic resonance spectroscopy studies examining this neurotransmission system, the results are inconsistent. Possible reasons for the inconsistency, including clinical features such as mood state and childhood versus adulthood age, were not addressed in previous meta-analyses. MethodsThis systematic review and meta-analysis of proton magnetic resonance spectroscopy studies of BD included 40 studies, with 1135 patients with BD and 964 healthy control (HC) subjects. ResultsGlutamate plus glutamine and glutamine levels in the anterior cingulate cortex of patients with BD were significantly elevated compared with those of HC subjects (standardized mean difference = 0.42, 0.48, respectively). Subgroup analyses showed that adult BD patients had significantly higher levels of glutamate plus glutamine than adult HC subjects, but this was not the case in pediatric patients. For mood states, anterior cingulate cortex glutamate plus glutamine levels were higher in patients with bipolar depression than those in HC subjects. ConclusionsOur results imply that glutamatergic dysfunction in the anterior cingulate cortex may be implicated in the pathophysiology of BD, which is most evident in adult BD patients and patients with bipolar depression.

Elevated GABA level in the precuneus and its association with pain intensity in patients with postherpetic neuralgia: An initial proton magnetic resonance spectroscopy study

PurposeThis study aimed to explore the changes in gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, and their correlations with clinical indicators in patients with postherpetic neuralgia (PHN). MethodsA totally of 22 PHN patients and 21 sex-, age-, and education-matched healthy controls (HCs) underwent proton magnetic resonance spectroscopy scanning. The spectral data of GABA in the precuneus was obtained by Mescher-Garwood point-resolved spectroscopy, whereas the spectral data of Glu, total N-acetyl-l-aspartic acid (tNAA) and total choline (tCho) were obtained by point-resolved spectroscopy. The pain intensity of PHN was assessed by numeric rating scales (NRS). The edited GABA signal was displayed as GABA+ due to overlapping macromolecules and homocarnosine signals. Total creatine (tCr) level in individual was used as an endogenous reference. The neurometabolites levels of PHN patients were compared with those of healthy individuals and the correlations with clinical variables (pain duration and intensity) were analyzed. ResultsPHN patients had higher GABA+/tCr levels in the precuneus than HCs (P = 0.009), with no significant differences in the levels of Glu/ tCr, tNAA/ tCr and tCho/ tCr (all P > 0.05). The GABA+/ tCr levels were positively correlated with the NRS scores of the PHN patients (r = 0.473, P = 0.030). ConclusionIncreased GABA+/tCr levels in the precuneus and their association with pain intensity of PHN patients suggested a key role of the abnormalities of regional GABAergic neurons in the pathophysiological mechanisms of pain in PHN.

In Vitro and in Vivo Evaluation of the Antimalarial Activities of Kniphofia reflexa Hutchinson ex Codd

In a phytochemical investigation of the rhizomes of Kniphofia reflexa, an endemic plant used to treat relapsing fevers in Kejom, northwestern Cameroon, 12 known (1-12) compounds were obtained following chromatographic methods and purification, together with 3 new derivatives (13-15) prepared by acetylation. One-dimensional and 2-dimensional nuclear magnetic resonance spectroscopic studies together with infrared and ultraviolet spectral analyses in association with data found in the literature were used to determine the structure of the compounds. In the in vitro evaluation of compounds 1-9, 12-14, and the crude extract against Plasmodium falciparum chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains, cassiamin C (1) [IC50 0.57 ± 0.54 (D6); 0.78 ± 0.08 (W2)], and crude extract [IC50 1.06 ± 0.22 (D6); 1.08 ± 0.12 (W2)] were highly active against the parasites. Kniphofiarexine (12) was inactive. However, its derivative, kniphofiarexine B (14), was moderately active. In the in vivo studies, the extract suppressed Plasmodium berghei growth, but did not clear completely the parasites.

Gamma-aminobutyric acid (GABA) levels in the midcingulate cortex and clozapine response in patients with treatment-resistant schizophrenia: A proton magnetic resonance spectroscopy (1 H-MRS) study.

Gamma-Aminobutyric Acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABAergic dysfunction has been implicated in the pathophysiology of schizophrenia. Clozapine, the only approved drug for treatment-resistant schizophrenia (TRS), involves the GABAergic system as one of its targets. However, no studies have investigated the relationship between brain GABA levels, as measured by proton magnetic resonance spectroscopy (1 H-MRS), and clozapine response in patients with TRS. This study enrolled patients with TRS who did not respond to clozapine (ultra-resistant schizophrenia: URS) and who responded to clozapine (non-URS), patients with schizophrenia who responded to first-line antipsychotics (first-line responders: FLR), and healthy controls (HCs). We measured GABA levels in the midcingulate cortex (MCC) using 3T 1 H-MRS and compared these levels among the groups. The associations between GABA levels and symptom severity were also explored within the patient groups. A total of 98 participants (URS: n=22; non-URS: n=25; FLR: n=16; HCs: n=35) completed the study. We found overall group differences in MCC GABA levels (F(3,86)=3.25, P=0.04). Specifically, patients with URS showed higher GABA levels compared to those with non-URS (F(1,52)=8.40, P=0.03, Cohen's d=0.84). MCC GABA levels showed no associations with any of the symptom severity scores within each group or the entire patient group. Our study is the first to report elevated GABA levels in the MCC in patients with schizophrenia resistant to clozapine treatment compared with those responsive to clozapine. Longitudinal studies are required to evaluate if GABA levels are a suitable biomarker to predict clozapine resistance.

Rapid adsorption of some heavy metals using extracted chitosan anchored with new aldehyde to form a schiff base.

A new aldehyde 2,2’-[propane-1,3-diylbis(oxy)] dibenzaldehyde was synthesized from refluxing 2-hydroxy acetophenone and 2-hydroxy 1,3-dichloropropanean in an alcoholic medium. The compositions and properties of the new aldehyde compound were characterized by elemental analysis, FTIR, and nuclear magnetic resonance spectroscopy studies. The extracted chitosan was made to react with a new aldehyde to form a Schiff base by a suitable method. The effects of initial concentration of metal ions, exposure time, imine weight, and pH on the adsorption of Cu(II), Cr(III), and Zn(II) metal ions were examined. An adsorption batch experiment was conducted. The adsorption process followed a second-order reaction and Langmuir model with qe 25 mg/g, 121 mg/g, and 26.31 mg/g for Cu(II), Zn(II), and Cr(III) respectively. The Gibbs free energy showed a negative value and the adsorption/desorption tests provided a high value 5 times.