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https://read.qxmd.com/read/30744104/neurodegeneration-with-brain-iron-accumulation-disorders-valuable-models-aimed-at-understanding-the-pathogenesis-of-iron-deposition
#1
REVIEW
Sonia Levi, Valeria Tiranti
Neurodegeneration with brain iron accumulation (NBIA) is a set of neurodegenerative disorders, which includes very rare monogenetic diseases. They are heterogeneous in regard to the onset and the clinical symptoms, while the have in common a specific brain iron deposition in the region of the basal ganglia that can be visualized by radiological and histopathological examinations. Nowadays, 15 genes have been identified as causative for NBIA, of which only two code for iron-proteins, while all the other causative genes codify for proteins not involved in iron management...
February 9, 2019: Pharmaceuticals
https://read.qxmd.com/read/30736288/curcumin-and-epigallocatechin-3-gallate-protect-murine-min6-pancreatic-beta-cells-against-iron-toxicity-and-erastin-induced-ferroptosis
#2
Tugba Kose, Mayra Vera-Aviles, Paul A Sharp, Gladys O Latunde-Dada
Ferroptosis is a form of programmed cell death that is characterized by lipid peroxidation and is inducible by iron and the accumulation of reactive oxygen species (ROS). It is triggered by erastin but inhibited by antioxidants such as -tocopherol, -carotene, polyphenols, and iron chelators such as deferoxamine (DFO), nitrilotriacetic acid (NTA), and ethylenediaminetetraacetic acid (EDTA). This study investigated the protective effects of two polyphenols, curcumin and (-)- epigallocatechin-3-gallate (EGCG), against iron loading and erastin-mediated ferroptosis in MIN6 cells...
February 6, 2019: Pharmaceuticals
https://read.qxmd.com/read/30717379/camphor-applied-epidermally-to-the-back-causes-snout-and-chest-grooming-in-rats-a-response-mediated-by-cutaneous-trp-channels
#3
Débora T Ishikawa, Robson Cristiano Lillo Vizin, Cristiane Oliveira de Souza, Daniel Carneiro Carrettiero, Andrej A Romanovsky, Maria Camila Almeida
Thermoregulatory grooming, a behavioral defense against heat, is known to be driven by skin-temperature signals. Because at least some thermal cutaneous signals that drive heat defenses are likely to be generated by transient receptor potential (TRP) channels, we hypothesized that warmth-sensitive TRPs drive thermoregulatory grooming. Adult male Wistar rats were used. We showed that camphor, a nonselective agonist of several TRP channels, including vanilloid (V) 3, when applied epidermally to the back (500 mg/kg), caused a pronounced self-grooming response, including paw-licking and snout- and chest-"washing"...
February 2, 2019: Pharmaceuticals
https://read.qxmd.com/read/30717260/modulators-of-transient-receptor-potential-trp-channels-as-therapeutic-options-in-lung-disease
#4
REVIEW
Alexander Dietrich
The lungs are essential for gas exchange and serve as the gateways of our body to the external environment. They are easily accessible for drugs from both sides, the airways and the vasculature. Recent literature provides evidence for a role of Transient Receptor Potential (TRP) channels as chemosensors and essential members of signal transduction cascades in stress-induced cellular responses. This review will focus on TRP channels (TRPA1, TRPC6, TRPV1, and TRPV4), predominantly expressed in non-neuronal lung tissues and their involvement in pathways associated with diseases like asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), lung fibrosis, and edema formation...
February 1, 2019: Pharmaceuticals
https://read.qxmd.com/read/30699979/correction-mateusz-s-et-al-iron-supplementation-in-suckling-piglets-an-ostensibly-easy-therapy-of-neonatal-iron-deficiency-anemia-pharmaceuticals-2018-11-128
#5
Mateusz Szudzik, Rafał R Starzyński, Aneta Jończy, Rafał Mazgaj, Małgorzata Lenartowicz, Paweł Lipiński
The authors wish to make the following corrections to this paper [¹]: the term "liposomal" should be replaced with the term "sucrosomial" in the following places [...].
January 29, 2019: Pharmaceuticals
https://read.qxmd.com/read/30691175/on-the-absolute-stereochemistry-of-tolterodine-a-circular-dichroism-study
#6
Marcin Górecki, Valerio Zullo, Anna Iuliano, Gennaro Pescitelli
Tolterodine ( 1 ) is a potent muscarinic receptor antagonist used in the treatment of overactive urinary bladder (OAB) syndrome. Tolterodine is chiral and it was patented, and is currently marketed, as the l-tartrate salt of the ( R )-enantiomer. However, the existing literature does not offer an ultimate proof of a stereoselective mode of action of 1 . A second open stereochemical issue concerns the absolute configuration (AC) of 1 . Neither the original patents nor subsequent studies have established the AC of 1 in an unambiguous way, although the AC of the l-tartrate salt of 1 was assigned by X-ray diffractometry...
January 26, 2019: Pharmaceuticals
https://read.qxmd.com/read/30691028/identification-of-potential-inhibitors-from-pyriproxyfen-with-insecticidal-activity-by-virtual-screening
#7
Ryan da Silva Ramos, Josivan da Silva Costa, Rai Campos Silva, Glauber Vilhena da Costa, Alex Bruno Lobato Rodrigues, Érica de Menezes Rabelo, Raimundo Nonato Picanço Souto, Carlton Anthony Taft, Carlos Henrique Tomich de Paula da Silva, Joaquín Maria Campos Rosa, Cleydson Breno Rodrigues Dos Santos, Williams Jorge da Cruz Macêdo
Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected...
January 25, 2019: Pharmaceuticals
https://read.qxmd.com/read/30682830/trpv1-inhibits-the-ventilatory-response-to-hypoxia-in-adult-rats-but-not-the-co%C3%A2-drive-to-breathe
#8
Luis Gustavo A Patrone, Jaime B Duarte, Kênia Cardoso Bícego, Alexandre A Steiner, Andrej A Romanovsky, Luciane H Gargaglioni
Receptors of the transient receptor potential (TRP) channels superfamily are expressed in many tissues and have different physiological functions. However, there are few studies investigating the role of these channels in cardiorespiratory control in mammals. We assessed the role of central and peripheral TRPV1 receptors in the cardiorespiratory responses to hypoxia (10% O₂) and hypercapnia (7% CO₂) by measuring pulmonary ventilation ( V ˙ E ), heart rate (HR), mean arterial pressure (MAP) and body temperature (Tb) of male Wistar rats before and after intraperitoneal (AMG9810 [2...
January 24, 2019: Pharmaceuticals
https://read.qxmd.com/read/30678341/-177-lu-lu-psma-617-salivary-gland-uptake-characterized-by-quantitative-in-vitro-autoradiography
#9
Roswitha Tönnesmann, Philipp T Meyer, Matthias Eder, Ann-Christin Baranski
Irradiation of salivary glands remains the main dose-limiting side effect of therapeutic PSMA-inhibitors, especially when using alpha emitters. Thus, further advances in radiopharmaceutical design and therapy strategies are needed to reduce salivary gland uptake, thereby allowing the administration of higher doses and potentially resulting in improved response rates and better tumor control. As the uptake mechanism remains unknown, this work investigates the salivary gland uptake of [177 Lu]Lu-PSMA-617 by autoradiography studies on pig salivary gland tissue and on PSMA-overexpressing LNCaP cell membrane pellets...
January 24, 2019: Pharmaceuticals
https://read.qxmd.com/read/30678075/l-ferritin-one-gene-five-diseases-from-hereditary-hyperferritinemia-to-hypoferritinemia-report-of-new-cases
#10
Beatriz Cadenas, Josep Fita-Torró, Mar Bermúdez-Cortés, Inés Hernandez-Rodriguez, José Luis Fuster, María Esther Llinares, Ana María Galera, Julia Lee Romero, Santiago Pérez-Montero, Cristian Tornador, Mayka Sanchez
Ferritin is a multimeric protein composed of light (L-ferritin) and heavy (H-ferritin) subunits that binds and stores iron inside the cell. A variety of mutations have been reported in the L-ferritin subunit gene ( FTL gene) that cause the following five diseases: (1) hereditary hyperferritinemia with cataract syndrome (HHCS), (2) neuroferritinopathy, a subtype of neurodegeneration with brain iron accumulation (NBIA), (3) benign hyperferritinemia, (4) L-ferritin deficiency with autosomal dominant inheritance, and (5) L-ferritin deficiency with autosomal recessive inheritance...
January 23, 2019: Pharmaceuticals
https://read.qxmd.com/read/30678034/can-the-efficacy-of-18-f-fdg-pet-ct-in-clinical-oncology-be-enhanced-by-screening-biomolecular-profiles
#11
REVIEW
Hazel O'Neill, Vinod Malik, Ciaran Johnston, John V Reynolds, Jacintha O'Sullivan
Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncology. Over the years the sensitivity and specificity of PET has improved with the advent of specific radiotracers, increased technical accuracy of PET scanners and incremental experience of Radiologists. However, significant limitations exist-most notably false positives and false negatives. Additionally, the accuracy of PET varies between cancer types and in some cancers, is no longer considered a standard imaging modality...
January 23, 2019: Pharmaceuticals
https://read.qxmd.com/read/30669484/micellisation-mechanism-and-behaviour-of-soluplus%C3%A2-%C3%A2-furosemide-micelles-preformulation-studies-of-an-oral-nanocarrier-based-system
#12
Julia F Alopaeus, Ellen Hagesæther, Ingunn Tho
: In this study, self-assembling Soluplus® micelles were examined for inherent properties. Through calorimetric analysis, the critical micelle concentration (CMC) could be determined at 25 and 37 °C, and the influence of three media (Milli-Q water, phosphate-buffered saline (PBS) with a pH of 7.4 and 0.1 M HCl) on the lower critical solution temperature (LCST) was detected. Furthermore, the solubilisation of a poorly soluble drug, furosemide, into the Soluplus® micelles was studied. The concentration-dependent properties of the micellar system were assessed through an examination of the micellar size, polydispersity, morphology, viscosity and solubilising properties, which were all found to be affected by the concentration, but temperature, pH and the composition of the test medium were also found to have an effect...
January 19, 2019: Pharmaceuticals
https://read.qxmd.com/read/30658444/structural-and-in-vitro-functional-comparability-analysis-of-altebrel%C3%A2-a-proposed-etanercept-biosimilar-focus-on-primary-sequence-and-glycosylation
#13
Ramin Fazel, Yudong Guan, Behrouz Vaziri, Christoph Krisp, Laura Heikaus, Amirhossein Saadati, Siti Nurul Hidayah, Manasi Gaikwad, Hartmut Schlüter
The demand for reliable comparability studies of biosimilars grows with their increased market share. These studies focus on physicochemical, structural, functional and clinical properties to ensure that a biosimilar has no significant differences to the originator product and can be released into the market without extensive clinical trials. In the current study, Enbrel® (etanercept, the originator) and Altebrel™ (the proposed biosimilar) underwent direct comparison. "Bottom-up" mass spectrometric analysis was used for primary sequence analysis, evaluation of N/O-glycosylation sites and quantification of methionine oxidation...
January 17, 2019: Pharmaceuticals
https://read.qxmd.com/read/30650563/cholecystokinin-2-receptor-targeting-with-novel-c-terminally-stabilized-hynic-minigastrin-analogs-radiolabeled-with-technetium-99m
#14
Maximilian Klingler, Christine Rangger, Dominik Summer, Piriya Kaeopookum, Clemens Decristoforo, Elisabeth von Guggenberg
The high overexpression of cholecystokinin-2 receptors (CCK2R) in tumors, such as medullary thyroid carcinoma, allows for highly specific diagnostic and therapeutic targeting with radiolabeled peptide probes derived from natural ligands for the receptor. Based on the ideal imaging characteristics, high availability and low cost of technetium-99m (99m Tc)-labeled radiopharmaceuticals we have developed two hydrazinonicotinic acid (HYNIC) conjugated minigastrin analogs allowing labeling at high specific activity...
January 15, 2019: Pharmaceuticals
https://read.qxmd.com/read/30646635/optimization-of-the-automated-synthesis-of-11c-mhed-administered-and-apparent-molar-activities
#15
Chrysoula Vraka, Verena Pichler, Neydher Berroterán-Infante, Tim Wollenweber, Anna Pillinger, Maximilian Hohensinner, Lukas Fetty, Dietrich Beitzke, Xiang Li, Cecile Philippe, Katharina Pallitsch, Markus Mitterhauser, Marcus Hacker, Wolfgang Wadsak
The tracer [[11C] meta -Hydroxyephedrine ([[11C] m HED) is one of the most applied PET tracers for cardiac imaging, whose radiosynthesis was already reported in 1990. While not stated in the literature, separation difficulties and an adequate formulation of the product are well known challenges in its production. Furthermore, the precursor (metaraminol) is also a substrate for the norepinephrine transporter, and can therefore affect the image quality. This study aims at optimizing the synthetic process of [[11C] m HED and investigating the effect of the apparent molar activity (sum of m HED and metaraminol) in patients and animals...
January 14, 2019: Pharmaceuticals
https://read.qxmd.com/read/30634637/the-therapeutic-potential-of-naringenin-a-review-of-clinical-trials
#16
REVIEW
Bahare Salehi, Patrick Valere Tsouh Fokou, Mehdi Sharifi-Rad, Paolo Zucca, Raffaele Pezzani, Natália Martins, Javad Sharifi-Rad
Naringenin is a flavonoid belonging to flavanones subclass. It is widely distributed in several Citrus fruits, bergamot, tomatoes and other fruits, being also found in its glycosides form (mainly naringin). Several biological activities have been ascribed to this phytochemical, among them antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic and cardioprotective effects. Nonetheless, most of the data reported have been obtained from in vitro or in vivo studies. Although some clinical studies have also been performed, the main focus is on naringenin bioavailability and cardioprotective action...
January 10, 2019: Pharmaceuticals
https://read.qxmd.com/read/30625990/juvenile-arthritis-patients-suffering-from-chronic-inflammation-have-increased-activity-of-both-ido-and-gtp-ch1-pathways-but-decreased-bh4-efficacy-implications-for-well-being-including-fatigue-cognitive-impairment-anxiety-and-depression
#17
Gerdien A H Korte-Bouws, Eline Albers, Marije Voskamp, Hendrikus Hendriksen, Lidewij R de Leeuw, Onur Güntürkün, Sytze de Roock, Sebastiaan J Vastert, S Mechiel Korte
Juvenile idiopathic arthritis (JIA) represents joint inflammation with an unknown cause that starts before the age of 16, resulting in stiff and painful joints. In addition, JIA patients often report symptoms of sickness behavior. Recent animal studies suggest that proinflammatory cytokines produce sickness behavior by increasing the activity of indoleamine-2,3-dioxygenase (IDO) and guanosinetriphosphate⁻cyclohydrolase-1 (GTP⁻CH1). Here, it is hypothesized that inflammation in JIA patients enhances the enzymatic activity of IDO and GTP-CH1 and decreases the co-factor tetrahydrobiopterin (BH4)...
January 8, 2019: Pharmaceuticals
https://read.qxmd.com/read/30621060/the-multi-functional-calcium-calmodulin-stimulated-protein-kinase-camk-family-emerging-targets-for-anti-cancer-therapeutic-intervention
#18
REVIEW
Joshua S Brzozowski, Kathryn A Skelding
The importance of Ca2+ signalling in key events of cancer cell function and tumour progression, such as proliferation, migration, invasion and survival, has recently begun to be appreciated. Many cellular Ca2+ -stimulated signalling cascades utilise the intermediate, calmodulin (CaM). The Ca2+ /CaM complex binds and activates a variety of enzymes, including members of the multifunctional Ca2+ /calmodulin-stimulated protein kinase (CaMK) family. These enzymes control a broad range of cancer-related functions in a multitude of tumour types...
January 7, 2019: Pharmaceuticals
https://read.qxmd.com/read/30609832/radioligands-for-tropomyosin-receptor-kinase-trk-positron-emission-tomography-imaging
#19
REVIEW
Ralf Schirrmacher, Justin J Bailey, Andrew V Mossine, Peter J H Scott, Lena Kaiser, Peter Bartenstein, Simon Lindner, David R Kaplan, Alexey Kostikov, Gert Fricker, Anne Mahringer, Pedro Rosa-Neto, Esther Schirrmacher, Carmen Wängler, Björn Wängler, Alexander Thiel, Jean-Paul Soucy, Vadim Bernard-Gauthier
The tropomyosin receptor kinases family (TrkA, TrkB, and TrkC) supports neuronal growth, survival, and differentiation during development, adult life, and aging. TrkA/B/C downregulation is a prominent hallmark of various neurological disorders including Alzheimer's disease (AD). Abnormally expressed or overexpressed full-length or oncogenic fusion TrkA/B/C proteins were shown to drive tumorigenesis in a variety of neurogenic and non-neurogenic human cancers and are currently the focus of intensive clinical research...
January 3, 2019: Pharmaceuticals
https://read.qxmd.com/read/30609700/aptamer-based-diagnostics-and-therapeutics
#20
EDITORIAL
Sarah Shigdar
Aptamers were first described almost 30 years ago, with the publication of three separate research papers describing how a randomized library of RNA sequences could be incubated with a target to find a sequence that specifically binds via van der Waals forces, covalent and hydrogen bonding, and not Watson Crick base pairing [...].
January 2, 2019: Pharmaceuticals
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