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brain chemistry

Decai Tian, Xiaodong Zhu, Rong Xue, Peng Zhao, Yuanrong Yao
History In November 2012, a previously healthy 31-year-old woman was admitted to our hospital with a 2-month history of right-sided numbness, diplopia, and intermittent nausea and dizziness. She did not have a history of fever, weight loss, headache, photophobia, seizure, or extremity weakness. Physical examination revealed left abduction limitation and right-sided hypoesthesia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts, normal serum chemistry, and normal immune function...
November 2018: Radiology
Iwona Grabowska, Neha Sharma, Alina Vasilescu, Madalina Iancu, Gabriela Badea, Rabah Boukherroub, Satishchandra Ogale, Sabine Szunerits
Rapid and accurate diagnostic technologies for early-state identification of cardiovascular abnormalities have become of high importance to prevent and attenuate their progression. The capability of biosensors to determine an increase in the concentration of cardiovascular protein biomarkers in circulating blood immediately after a myocardial infarction makes them ideal point-of-care platforms and alternative approaches to electrocardiograms, chest X-rays, and different laboratory-based immunoassays. We report here a generic approach toward multianalyte sensing platforms for cardiac biomarkers by developing aptamer-based electrochemical sensors for brain natriuretic peptide (BNP-32) and cardiac troponin I (cTnI)...
September 30, 2018: ACS Omega
Gregory C Shearer, Rachel E Walker
Oxylipins are lipid mediators produced from polyunsaturated fatty acid (PUFA) metabolism, and are thought to be a molecular explanation for the diverse biological effects of PUFAs. Like PUFAs, oxylipins are distinguished by their omega-6 (n6) or omega-3 (n3) chemistry. We review the use of n6 oxylipins as biomarkers of disease and their use in diagnosis and risk assessment. We show cases where oxylipins derived from linoleate (LA) or arachidonate (AA) produced by the activities of lipoxygenase, cyclooxygenase, epoxygenase, ω/ω-1 hydroxylase, and autooxidation are useful as biomarkers or risk markers...
October 2018: Prostaglandins, Leukotrienes, and Essential Fatty Acids
C I Edvard Smith, Rula Zain
Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, spliceswitching ONs, and short interfering RNA drugs have been successfully developed. Moreover, antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNAdecoys, DNAzymes, synthetic guide strands for CRISPR/Cas, and innate immunity-stimulating ONs are all in clinical trials. DNAtargeting, triplex-forming ONs and strand-invading ONs have made their mark on drug development research, but not yet as medicines...
October 4, 2018: Annual Review of Pharmacology and Toxicology
Lorenzo Massimi, Inna Bukreeva, Giulia Santamaria, Michela Fratini, Alessandro Corbelli, Francesco Brun, Stefano Fumagalli, Laura Maugeri, Alexandra Pacureanu, Peter Cloetens, Nicola Pieroni, Fabio Fiordaliso, Gianluigi Forloni, Antonio Uccelli, Nicole Kerlero de Rosbo, Claudia Balducci, Alessia Cedola
Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder associated with aberrant production of beta-amyloid (Aβ) peptide depositing in brain as amyloid plaques. While animal models allow investigation of disease progression and therapeutic efficacy, technology to fully dissect the pathological mechanisms of this complex disease at cellular and vascular levels is lacking. X-ray phase contrast tomography (XPCT) is an advanced non-destructive 3D multi-scale direct imaging from the cell through to the whole brain, with exceptional spatial and contrast resolution...
September 18, 2018: NeuroImage
Federico Baruffaldi, April Huseby Kelcher, Megan Laudenbach, Valeria Gradinati, Ajinkya Limkar, Michaela Roslawski, Angela Birnbaum, Andrew Lees, Carla Hassler, Scott P Runyon, Marco Pravetoni
Vaccines may offer a new treatment strategy for opioid use disorders and opioid-related overdoses. To speed translation, this study evaluates opioid conjugate vaccines containing components suitable for pharmaceutical manufacturing and compares analytical assays for conjugate characterization. Three oxycodone-based haptens (OXY) containing either PEGylated or tetraglycine [(Gly)4] linkers were conjugated to keyhole limpet hemocyanin (KLH) carrier protein via carbodiimide (EDAC) or maleimide chemistry. The EDAC-conjugated OXY(Gly)4-KLH was most effective in reducing oxycodone distribution to the brain in mice...
September 21, 2018: Molecular Pharmaceutics
Anika Westphal, Ralf Mrowka
Hormones: They control the human circadian rhythm, cause happiness after physical exercise, cause butterflies in one's stomach and contribute to the chemistry of love, turn a pregnant woman's life upside down and influence the growth of the fetus, in short, they are essential in the human individual development and homeostasis of organs. Hormones are mainly produced in the brain, pancreas, thyroid, kidney and the genital organs and represent the most important chemical messengers in the human organism. Hormone-dependent pathologic conditions are manifold and dysregulations need to be treated in order to warrant a healthy human body...
September 21, 2018: Acta Physiologica
Monika Rana, Anuj Kumar Sharma
The coordination chemistry of transition metal ions (Fe, Cu, Zn) with the amyloid-β (Aβ) peptides has attracted a lot of attention in recent years due to its repercussions in Alzheimer's disease (AD). Aβ peptide undergoes self-aggregation to form amyloid plaques and soluble oligomers, which are believed to play a central role in AD pathology. Metal ions and Aβ-metal adducts can generate toxic radical species capable of modifying biomolecules, ultimately causing death of the neuronal cells. The impact of these metal ions on Aβ aggregation and neurotoxic species formation is still not well understood...
September 20, 2018: Metallomics: Integrated Biometal Science
Sridhar T Narla, Brandon Decker, Pinaki Sarder, Ewa K Stachowiak, Michal K Stachowiak
Schizophrenia is a neurodevelopmental disorder characterized by complex aberrations in the structure, wiring, and chemistry of multiple neuronal systems. The abnormal developmental trajectory of the brain is established during gestation, long before clinical manifestation of the disease. Over 200 genes and even greater numbers of single nucleotide polymorphisms and copy number variations have been linked with schizophrenia. How does altered function of such a variety of genes lead to schizophrenia? We propose that the protein products of these altered genes converge on a common neurodevelopmental pathway responsible for the development of brain neural circuit and neurotransmitter systems...
2018: Results and Problems in Cell Differentiation
Kenneth Blum, Edward J Modestino, Marjorie Gondré-Lewis, B William Downs, David Baron, Bruce Steinberg, David Siwicki, John Giordano, Thomas McLaughlin, Jennifer Neary, Mary Hauser, Lyle Fried, Rajendra D Badgaiyan
The well-researched pro-dopamine regulator KB220 and variants result in increased functional connectivity in both animal and human brains, and prolonged neuroplasticity (brain cell repair) having been observed in rodents. Moreover, in addition to increased functional connectivity, recent studies show that KB220Z increases overall brain connectivity volume, enhances neuronal dopamine firing, and eliminates lucid dreams in humans over a prolonged period. An unprecedented number of clinical studies validating this patented nutrigenomic technology in re-balancing brain chemistry and optimizing dopamine sensitivity and function have been published...
November 2017: Journal of Systems and Integrative Neuroscience
Watshara Shoombuatong, Nalini Schaduangrat, Chanin Nantasenamat
Aromatase is a rate-limiting enzyme for estrogen biosynthesis that is overproduced in breast cancer tissue. To block the growth of breast tumors, aromatase inhibitors (AIs) are employed to bind and inhibit aromatase in order to lower the amount of estrogen produced in the body. Although a number of synthetic aromatase inhibitors have been released for clinical use in the treatment of hormone-receptor positive breast cancer, these inhibitors may lead to undesirable side effects (e.g. increased rash, diarrhea and vomiting; effects on the bone, brain and heart) and therefore, the search for novel AIs continues...
2018: EXCLI Journal
Di Wu, Na Hu, Jichao Liu, Guangsen Fan, Xiuting Li, Jing Sun, Chunji Dai, Yourui Suo, Guoliang Li, Yongning Wu
Recently, exploitation of nanozymes for signal amplification has aroused extensive research interesting in the fields of analytical chemistry and nanoscience. Herein, we introduced a new sensing strategy based on the ascorbic acid (AA) precisely regulated Ag3 PO4 nanozyme for signal amplification. AA can reduce the partial Ag+ on the surface of Ag3 PO4 nano-particles to form Ag° particles and result in the formation of Ag°/Ag3 PO4 heterostructure. Due to surface plasmon resonance (SPR), the Ag° particles in heterostructure can act as the co-catalysts to enhance the electron-hole separation and the interfacial charge transfer, leading to a highly efficient oxidase mimicking activity for catalyzing the oxidation of the substrate of 3,3,5,5-tetramethylbenzidine (TMB) under visible light...
December 1, 2018: Talanta
Tejal Aslesh, Rika Maruyama, Toshifumi Yokota
Spinal muscular atrophy (SMA) is the most common genetic cause of infantile death caused by mutations in the SMN1 gene. Nusinersen (Spinraza), an antisense therapy-based drug with the 2'-methoxyethoxy (2'MOE) chemistry approved by the FDA in 2016, brought antisense drugs into the spotlight. Antisense-mediated exon inclusion targeting SMN2 leads to SMN protein expression. Although effective, 2'MOE has weaknesses such as the inability to cross the blood-brain barrier and the high cost of treatment. To investigate new chemistries of antisense oligonucleotides (ASOs), SMA mouse models can serve as an important source...
2018: Methods in Molecular Biology
Aleksander Touznik, Rika Maruyama, Toshifumi Yokota
Spinal muscular atrophy (SMA), the most common gentic cause of infantile death caused by mutations in the SMN1 gene, presents a unique case in the field of splice modulation therapy, where a gene (or lack of) is responsible for causing the disease phenotype but treatment is not focused around it. Antisense therapy targeting SMN2 which leads to SMN protein expression has been at the forefront of research when it comes to developing a feasible therapy for treating SMA. Recent FDA approval of an antisense-based drug with the 2'-methoxyethoxy (2'MOE) chemistry, called nusinersen (Spinraza), brought antisense drugs into the spotlight...
2018: Methods in Molecular Biology
Shiyang Zhou, Guangying Chen, Gangliang Huang
In the studied a series novel of lazabemide derivatives were designed, synthesized and evaluated as inhibitors of monoamine oxidase (MAO-A or MAO-B). These compounds used lazabemide as the lead compound, and the chemistry structures were modified by used the bioisostere and modification of compound with alkyl principle. The two types of inhibitors (inhibition of MAO-A and inhibition of MAO-B) were screened by inhibition activity of MAO. In vitro experiments showed that compounds 3a, 3d and 3f had intensity inhibition the biological activity of MAO-A, while compounds 3i and 3m had intensity inhibition the biological activity of MAO-B...
August 19, 2018: Bioorganic & Medicinal Chemistry
Feten Najlaoui, Pascal Pigeon, Sonia Aroui, Mylène Pezet, Lucie Sancey, Naziha Marrakchi, Ali Rhouma, Gérard Jaouen, Michel De Waard, Benoit Busser, Stéphane Gibaud
OBJECTIVE: We synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection-enhanced delivery (CED) as a strategy for delivery. METHODS: To overcome the issue of their poor solubility, these ferrocenyl-tamoxifen derivatives were esterified and encapsulated into different nanocarriers, that is lipid (LNC) and polymeric nanocapsules (PNL-NC). We describe the chemistry, the encapsulation and the physicochemical characterization of these formulations...
August 23, 2018: Journal of Pharmacy and Pharmacology
Jin-Seok Lee, Won-Yong Kim, Yoo-Jin Jeon, Sam-Keun Lee, Chang-Gue Son
An imbalance between excitatory and inhibitory neurotransmitters is known to induce neuronal excitotoxicity which is a major cause of neurodegenerative disorders. Excessive glutamate concentration leads to the neuronal death by increasing oxidative stress and affecting the apoptotic signaling pathway. We investigated the anti-excitotoxic effects and associated working mechanisms of 30% ethanol extract of Aquilariae Lignum (ALE) against hippocampal neuronal death by glutamate. HT22 cells were treated with glutamate (20 mM) for 24 h following pretreatment with ALE (5, 10, 25 μg/mL)...
October 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Abhishek Manoj Ranaware, Kishore Banik, Vishwas Deshpande, Ganesan Padmavathi, Nand Kishor Roy, Gautam Sethi, Lu Fan, Alan Prem Kumar, Ajaikumar B Kunnumakkara
The past few decades have witnessed widespread research to challenge carcinogenesis; however, it remains one of the most important health concerns with the worst prognosis and diagnosis. Increasing lines of evidence clearly show that the rate of cancer incidence will increase in future and will create global havoc, designating it as an epidemic. Conventional chemotherapeutics and treatment with synthetic disciplines are often associated with adverse side effects and development of chemoresistance. Thus, discovering novel economic and patient friendly drugs that are safe and efficacious is warranted...
August 10, 2018: International Journal of Molecular Sciences
Matthew G Stovell, Marius O Mada, Adel Helmy, T Adrian Carpenter, Eric P Thelin, Jiun-Lin Yan, Mathew R Guilfoyle, Ibrahim Jalloh, Duncan J Howe, Peter Grice, Andrew Mason, Susan Giorgi-Coll, Clare N Gallagher, Michael P Murphy, David K Menon, Peter J Hutchinson, Keri L H Carpenter
A key pathophysiological process and therapeutic target in the critical early post-injury period of traumatic brain injury (TBI) is cell mitochondrial dysfunction; characterised by elevation of brain lactate/pyruvate (L/P) ratio in the absence of hypoxia. We previously showed that succinate can improve brain extracellular chemistry in acute TBI, but it was not clear if this translates to a change in downstream energy metabolism. We studied the effect of microdialysis-delivered succinate on brain energy state (phosphocreatine/ATP ratio (PCr/ATP)) with 31 P MRS at 3T, and tissue NADH/NAD+ redox state using microdialysis (L/P ratio) in eight patients with acute major TBI (mean 7 days)...
July 24, 2018: Scientific Reports
Niels Hadrup, Katrin Loeschner, Karen Mandrup, Gitte Ravn-Haren, Henrik L Frandsen, Erik H Larsen, Henrik R Lam, Alicja Mortensen
Selenium (Se) nanoparticles have been proposed as food supplements. However, the particle formulation may exert unexpected toxicity. The aim was therefore to compare toxicity of low doses of Se nanoparticles and the dissolved, ionized Se species selenite. Female rats were dosed orally for 28 d with either: 0.05, 0.5, or 4 mg Se/kg body weight (bw)/day as 20 nm Se nanoparticles or 0.05 or 0.5 mg Se/kg bw/day as sodium selenite. Male rats were dosed 4 mg Se/kg bw/day as Se nanoparticles. Body weight and clinical appearance were recorded throughout the experiment...
July 23, 2018: Drug and Chemical Toxicology
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