scholarly journals GABA quantification in human anterior cingulate cortex

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0240641
Author(s):  
Jan Weis ◽  
Jonas Persson ◽  
Andreas Frick ◽  
Fredrik Åhs ◽  
Maarten Versluis ◽  
...  
Keyword(s):  
Anterior Cingulate ◽  
Basis Set ◽  
Rf Pulses ◽  
Total N ◽  
Inhibitory Neurotransmitter ◽  
Relaxation Effects ◽  
Internal Concentration ◽  
Good Potential ◽  
Total Creatine

γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B0 drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation.

scholarly journals GABA quantification in human anterior cingulate cortex

2020 ◽  
Author(s):  
Jan Weis ◽  
Jonas Persson ◽  
Andreas Frick ◽  
Fredrik Åhs ◽  
Maarten Versluis ◽  
...  
Keyword(s):  
Anterior Cingulate ◽  
Basis Set ◽  
Rf Pulses ◽  
Total N ◽  
Inhibitory Neurotransmitter ◽  
Relaxation Effects ◽  
Internal Concentration ◽  
Good Potential ◽  
Total Creatine

Abstractγ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B0 drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation.

scholarly journals Purification, structure and anti-oxidation of polysaccharides from the fruit of Nitraria tangutorum Bobr.

RSC Advances ◽  
2018 ◽  
Vol 8 (21) ◽  
pp. 11731-11743 ◽  
Author(s):  
Baotang Zhao ◽  
Jing Liu ◽  
Xin Chen ◽  
Ji Zhang ◽  
Junlong Wang
Keyword(s):  
Antioxidant Activity ◽  
Food Industry ◽  
Natural Antioxidant ◽  
Nitraria Tangutorum ◽  
Good Potential

Antioxidant activity of NTWP-II, evaluated in vitro, indicates that NTWP-II has good potential as a natural antioxidant used in the food industry.

Drug-eluting microneedles for self-administered treatment of keloids

TECHNOLOGY ◽  
2014 ◽  
Vol 02 (02) ◽  
pp. 144-152 ◽  
Author(s):  
Peng Xue ◽  
David Chen Loong Yeo ◽  
Yon Jin Chuah ◽  
Hong Liang Tey ◽  
Yuejun Kang ◽  
...  
Keyword(s):  
Clinical Supervision ◽  
Fibrous Tissue ◽  
Polyethylene Glycol Diacrylate ◽  
Glycol Diacrylate ◽  
Keloid Fibroblast ◽  
Culture Models ◽  
Drug Eluting ◽  
Good Potential ◽  
Microneedle Patch

Keloid is a long-term dermatological scarring disease characterized by disfiguring lesions resulting from overgrowth of dense fibrous tissue. Current therapeutics are ineffective, require clinical supervision and can be costly. This study investigated the use of microneedle technology in the self-management of keloid lesions. Specifically, a microneedle patch comprising of polyethylene glycol diacrylate (PEGDA) and encapsulating 5-fluorouracil (5-FU) has been developed for transdermal delivery. The microneedle patches showed requisite mechanical strength (hardness 45 ± 11 MPa, elastic modulus 0.66 ± 0.16 GPa) and were able to puncture porcine epidermis. The choice of PEGDA substrate enabled conformability to non-planar anatomical regions (e.g. elbow), with about 50% of the loaded 5-FU released during the first 12 hours. Thereafter, the microneedle efficacy was evaluated on in vitro keloid fibroblast culture models, where 5-FU loaded microneedles effectively abolished keloid fibroblast proliferation activity. In summary, we have developed a microneedle device with a good potential as an effective, economical and self-applied therapy for keloid scars.

scholarly journals Perinatal fentanyl exposure leads to long-lasting impairments in somatosensory circuit function and behavior

2020 ◽  
Author(s):  
Jason Alipio ◽  
Catherine Haga ◽  
Megan E Fox ◽  
Keiko Arakawa ◽  
Rakshita Balaji ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Morphological Changes ◽  
Anterior Cingulate ◽  
Preclinical Model ◽  
Sensory Stimuli ◽  
Synaptic Excitation ◽  
Molecular Abnormalities ◽  
Postsynaptic Currents ◽  
And Behavior

One consequence of the opioid epidemic are lasting neurodevelopmental sequelae afflicting adolescents exposed to opioids in the womb. A translationally relevant and developmentally accurate preclinical model is needed to understand the behavioral, circuit, network, and molecular abnormalities resulting from this exposure. By employing a novel preclinical model of perinatal fentanyl exposure, our data reveal that fentanyl has several dose-dependent, developmental consequences to somatosensory function and behavior. Newborn male and female mice exhibit signs of withdrawal and sensory-related deficits that extend at least to adolescence. As fentanyl exposure does not affect dams' health or maternal behavior, these effects result from the direct actions of perinatal fentanyl on the pups' developing brain. At adolescence, exposed mice exhibit reduced adaptation to sensory stimuli, and a corresponding impairment in primary somatosensory (S1) function. In vitro electrophysiology demonstrates a long-lasting reduction in S1 synaptic excitation, evidenced by decreases in release probability, NMDA receptor-mediated postsynaptic currents, and frequency of miniature excitatory postsynaptic currents, as well as increased frequency of miniature inhibitory postsynaptic currents. In contrast, anterior cingulate cortical neurons exhibit an opposite phenotype, with increased synaptic excitation. Consistent with these changes, electrocorticograms reveal suppressed ketamine-evoked γ oscillations. Morphological analysis of S1 pyramidal neurons indicate reduced dendritic complexity, dendritic length, and soma size. Further, exposed mice exhibited abnormal cortical mRNA expression of key receptors and neuronal growth and development, changes that were consistent with the electrophysiological and morphological changes. These findings demonstrate the lasting sequelae of perinatal fentanyl exposure on sensory processing and function.

Analysis of high PSA N-CAM expression during mammalian spinal cord and peripheral nervous system development

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 69-82 ◽  
Author(s):  
S. Boisseau ◽  
J. Nedelec ◽  
V. Poirier ◽  
G. Rougon ◽  
M. Simonneau
Keyword(s):  
Spinal Cord ◽  
Neural Crest ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Developmental Stages ◽  
System Development ◽  
Nervous System Development ◽  
Homogeneous Distribution ◽  
Total N

Using a monoclonal antibody that recognizes specifically a high polysialylated form of N-CAM (high PSA N-CAM), the temporal and spatial expression of this molecule was studied in developing spinal cord and neural crest derivatives of mouse truncal region. Temporal expression was analyzed on immunoblots of spinal cord and dorsal root ganglia (DRGs) extracts microdissected at different developmental stages. Analysis of the ratio of high PSA N-CAM to total N-CAM indicated that sialylation and desialylation are independently regulated from the expression of polypeptide chains of N-CAM. Motoneurons, dorsal root ganglia cells and commissural neurons present a homogeneous distribution of high PSA N-CAMs on both their cell bodies and their neurites. Sialylation of N-CAM can occur in neurons after their aggregation in peripheral ganglia as demonstrated for dorsal root ganglia at E12. Furthermore, peripheral ganglia express different levels of high PSA N-CAM. With in vitro models using mouse neural crest cells, we found that expression of high PSA N-CAM was restricted to cells presenting an early neuronal phenotype, suggesting a common regulation for the expression of high PSA N-CAM molecules, neurofilament proteins and sodium channels. Using perturbation experiments with endoneuraminidase, we confirmed that high PSA N-CAM molecules are involved in fasciculation and neuritic growth when neurons derived from neural crest grow on collagen substrata. However, we demonstrated that these two parameters do not appear to depend on high PSA N-CAM molecules when cells were grown on a fibronectin substratum, indicating the existence of a hierarchy among adhesion molecules.

Rapid Emergence of Daptomycin Resistance in Nonstriatum Corynebacterium Species: A Multicenter Study

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S32-S33
Author(s):  
Kaitlin Mitchell ◽  
Erin McElvania ◽  
Meghan Wallace ◽  
Amy Robertson ◽  
Lars Westblade ◽  
...  
Keyword(s):  
Multicenter Study ◽  
Tertiary Care ◽  
Total N ◽  
Gradient Diffusion ◽  
Corynebacterium Species ◽  
Short Period ◽  
High Level ◽  
Level Resistance

Abstract Members of the genus Corynebacterium are increasingly recognized as causes of opportunistic infection; some species can be multidrug resistant, posing a treatment challenge. Daptomycin is frequently used as therapy of last resort in this setting, but previous work from our group demonstrated the ability of C striatum clinical isolates to rapidly develop high-level resistance to daptomycin, both in vivo and in vitro. Here, our objective was to expand this investigation into a multicenter study evaluating multiple Corynebacterium species. Corynebacterium strains from three tertiary-care academic medical centers (total, n = 76; site 1, n = 44; site 2, n = 15; site 3, n = 17) were evaluated, representing 16 species. Isolates were identified during routine clinical testing and reported to species level in accordance with each laboratory’s standard operating procedures. Identification of each species was confirmed using both VITEK MS and Bruker BioTyper MALDI-TOF MS. MICs to daptomycin (Etest), vancomycin (Etest), and telavancin (Liofilchem) at baseline were determined using gradient diffusion methods on Mueller-Hinton agar with blood (Hardy Diagnostics). Each isolate was then inoculated in duplicate to 5 mL Tryptic Soy Broth. A daptomycin Etest was submerged in one tube from each pair, and growth was observed after 24-hour incubation. If turbidity was observed in the tube with daptomycin, MICs for each of the 3 antimicrobials were reassessed. High-level daptomycin resistance emerged in 24 strains: C aurimucosum (1/1 isolate tested), C bovis (1/2), C jeikeium (2/11), C macginleyi (3/3), C resistens (1/1), C simulans (1/1), C striatum (14/14 isolates), and C ulcerans (1/1). The majority of these isolates had MIC values >256 µg/mL following exposure to daptomycin. Forty-eight other isolates remained susceptible to daptomycin: C afermentans (1/1), C amycolatum (19/20), C diphtheriae (1/1), C jeikeium (7/11), C kroppenstedtii (2/2), C propinquum (3/3), C pseudodiphtheriticum (6/6), C tuberculostearicum (0/6), and C urealyticum (0/3). Many of these isolates did not undergo MIC testing postdaptomycin exposure in broth due to complete lack of growth. Among those that did (n = 19), the median daptomycin MIC was 0.38 µg/mL (mean 0.42 µg/mL; range 0.023-1.0 µg/mL). One isolate of C bovis and two isolates of C jeikeium yielded variable susceptibility to daptomycin; a subset of resistant colonies grew adjacent to the gradient diffusion strip. Upon isolation and further MIC testing, these colonies maintained high-level resistance. In addition, one isolate of C amycolatum exhibited high-level daptomycin resistance (MIC >256 µg/mL) prior to in vitro exposure. All isolates in the cohort were susceptible to vancomycin and telavancin, both before and after daptomycin exposure. Our findings suggest that multiple Corynebacterium species can rapidly develop high-level daptomycin resistance after a short period of exposure to this antimicrobial. This finding has important clinical implications, especially in the treatment of invasive infections or infections of indwelling medical devices.

scholarly journals Design, Synthesis, and In Vitro Evaluation of Hydroxybenzimidazole-Donepezil Analogues as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 985 ◽  
Author(s):  
Sílvia Chaves ◽  
Simonetta Resta ◽  
Federica Rinaldo ◽  
Marina Costa ◽  
Romane Josselin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroblastoma Cells ◽  
Biological Properties ◽  
Design Synthesis ◽  
Aβ Aggregation ◽  
Structural Isomerization ◽  
Good Potential ◽  
Nitro Derivatives

A series of multi-target-directed ligands (MTDLs), obtained by attachment of a hydroxyphenylbenzimidazole (BIM) unit to donepezil (DNP) active mimetic moiety (benzyl-piperidine/-piperazine) was designed, synthesized, and evaluated as potential anti-Alzheimer’s disease (AD) drugs in terms of biological activity (inhibition of acetylcholinesterase (AChE) and β–amyloid (Aβ) aggregation), metal chelation, and neuroprotection capacity. Among the DNP-BIM hybrids studied herein, the structural isomerization did not significantly improve the biological properties, while some substitutions, namely fluorine atom in each moiety or the methoxy group in the benzyl ring, evidenced higher cholinergic AChE activity. All the compounds are able to chelate Cu and Zn metal ions through their bidentate BIM moieties, but compound 5, containing a three-dentate chelating unit, is the strongest Cu(II) chelator. Concerning the viability on neuroblastoma cells, compounds 9 and 10 displayed the highest reduction of Aβ-induced cell toxicity. In silico calculations of some pharmacokinetic descriptors indicate that all the compounds but the nitro derivatives have good potential oral-bioavailability. Overall, it can be concluded that most of the studied DNP-BIM conjugates showed quite good anti-AD properties, therefore deserving to be considered in further studies with the aim of understanding and treating AD.

scholarly journals Potentials and Safety of Date Palm Fruit against Diabetes: A Critical Review

Foods ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1557
Author(s):  
Md Al-Tareq Mia ◽  
Md Golam Mosaib ◽  
Md Ibrahim Khalil ◽  
Md Asiful Islam ◽  
Siew Hua Gan
Keyword(s):  
Date Palm ◽  
Antioxidant Activities ◽  
Human Study ◽  
Insulin Receptors ◽  
Β Cells ◽  
Palm Fruit ◽  
Good Potential ◽  
Palm Fruits

Diabetes is a chronic metabolic disorder triggered by disturbances in carbohydrate, protein, and lipid metabolisms, where either reduced secretion or sensitivity of insulin is observed coupled with poor glucose control. Date palm fruits are one of the fruits reported to have good potential in diabetes treatment due to its presence of polyphenols exerting strong antioxidant activities. Other possible mechanisms of action include the polyphenolic compounds, which can inhibit enzymes like α-amylase and α-glucosidase. Flavonoids in dates can stimulate β-cells by increasing the number of islets and β-cells, recovering endocrine pancreatic tissues, reducing β-cell apoptosis, activating insulin receptors following the increase in insulin secretion, in addition to improving diabetes-induced complications. In this review, the in vitro, in vivo, and human study-based evidence of date palm as an anti-diabetic fruit is summarised.

scholarly journals Experimental and Theoretical Studies of Novel Azo Benzene Functionalized Conjugated Polymers: In-vitro Antileishmanial Activity and Bioimaging

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Neetika Singh ◽  
Mohd. Arish ◽  
Prabhat Kumar ◽  
Abdur Rub ◽  
Ufana Riaz
Keyword(s):  
Atomic Orbital ◽  
Uv Spectra ◽  
Basis Set ◽  
Fluorescence Studies ◽  
H Nmr ◽  
Transmission Electron ◽  
B3lyp Method ◽  
Vis Spectroscopy ◽  
Experimental Findings

AbstractTo study the effect of insertion of azobenzene moiety on the spectral, morphological and fluorescence properties of conventional conducting polymers, the present work reports ultrasound-assisted polymerization of azobenzene with aniline, 1-naphthylamine, luminol and o-phenylenediamine. The chemical structure and polymerization was established via Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (1H-NMR) spectroscopy, while the electronic properties were explored via ultraviolet-visible (UV-vis) spectroscopy. Theoretical IR and UV spectra were computed using DFT/B3LYP method with 6–311G basis set while theoretical 1H-NMR spectra was obtained by gauge independent atomic orbital (GIAO) method. The theoretically computed spectra were found to be in close agreement with the experimental findings confirming the chemical as well as electronic structure of the synthesized polymers. Morphology was investigated by X-ray diffraction and transmission electron microscopy studies. Fluorescence studies revealed emission ranging between 530–570 nm. The polymers also revealed high singlet oxygen (1O2) generation characteristics. In-vitro antileishmanial efficacy as well as live cell imaging investigations reflected the potential application of these polymers in the treatment of leishmaniasis and its diagnosis.

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