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Peripherial iv

Bianca N Mason, Eric A Kaiser, Adisa Kuburas, Maria-Cristina M Loomis, John A Latham, Leon F Garcia-Martinez, Andrew F Russo
: The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. While migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the central nervous system, we used CGRP-induced light aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal, IP) injection of CGRP resulted in light aversive behavior in wild-type CD1 mice similar to aversion previously seen following central (intracerebroventricular, ICV) injection...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Raissa Lerner, Julia Post, Sebastian Loch, Beat Lutz, Laura Bindila
Epilepsy is a highly common chronic neurological disorder, manifested in many different types, affecting ~1% of the worldwide human population. The molecular mechanisms of epileptogenesis has not yet been clarified, and pharmacoresistance exhibited by 30-40% of epilepsy patients remains a major obstacle in medical care. Growing evidence indicates a role of lipid signalling pathways in epileptogenesis, thus lipid signals emerge as potential biomarkers for the onset and evolving course of the epileptic disorder, as well as potential therapeutic agents and targets...
November 15, 2016: Biochimica et Biophysica Acta
Harry K W Kim, Jamie Burgess, Alec Thoveson, Paul Gudmundsson, Molly Dempsey, Chan-Hee Jo
BACKGROUND: Legg-Calvé-Perthes disease is a juvenile form of osteonecrosis of the femoral head. The purpose of this study was to use serial perfusion magnetic resonance imaging (MRI) to determine the pattern and rate of revascularization of the femoral heads of patients with the active stage of Legg-Calvé-Perthes disease. METHODS: We performed a prospective study of 29 patients (30 hips) with a mean age (and standard deviation) of 8.4 ± 1.9 years who were diagnosed with Waldenström Stage-1 or 2 Legg-Calvé-Perthes disease...
November 16, 2016: Journal of Bone and Joint Surgery. American Volume
Johannes Karlsson, Ann-Charlotte Dreifaldt, Louise Bohr Mordhorst, Bengt Sorbe
PURPOSE: To compare the clinical outcome of cervical cancer patients treated with primary radiotherapy with and without the addition of brachytherapy. METHODS AND MATERIALS: In all, 220 patients with cervical cancer stage I-IV treated between 1993 and 2009 were included. Three or five 6.0 Gy fractions of brachytherapy were given in addition to the external beam radiotherapy to 134 patients, whereas 86 patients received external beam radiotherapy alone (EBRTA). In the EBRTA group, the patients received external boost instead of brachytherapy with a total dose to the tumor of 64-72 Gy...
November 8, 2016: Brachytherapy
Sung Han Kim
Cytological changes of the epithelial cells according to the developmenatal phases of the seminal vesicle related to the spermatogenic stages in the testicular lobules during spermagenesis in male Neptunea (Barbitonia) cumingii (Gastropoda: Buccinidae) were investigated monthly by electron microscopical and histological observations. N. (B) cumingii is dioecious, and an internal fertilization species. The male genital organ is located near the tentacles. The spermatozoon is approximatley 50 μm in length. The axoneme of the tail flagellum consists of nine pairs of microtubles at the periphery and one pair at the center...
September 2016: Balsaeng'gwa Saengsig
P Holzer
The gut microbiota and the brain interact with each other through multiple bidirectional signaling pathways in which neuropeptides and neuroactive peptide messengers play potentially important mediator roles. Currently, six particular modes of a neuropeptide link are emerging. (i) Neuropeptides and neurotransmitters contribute to the mutual microbiota-host interaction. (ii) The synthesis of neuroactive peptides is influenced by microbial control of the availability of amino acids. (iii) The activity of neuropeptides is tempered by microbiota-dependent autoantibodies...
2016: International Review of Neurobiology
Weihong Pan, Abba J Kastin
Here we summarize three aspects of our understanding of the interactions of cytokines and neurotrophic peptides/proteins with the blood-brain and bloodspinal cord barriers (BBB): (a) pharmacokinetic analysis that has been reported for native cytokines and neurotrophic peptides/proteins; (b) landmark work on conjugated proteins to enhance their delivery across the normal BBB; and (c) regulatory changes under pathophysiological conditions in rodents, particularly after spinal cord injury (SCI). First, though the BBB restricts the permeation of large proteins, some cytokines and neurotrophic peptides/proteins in the periphery can reach the central nervous system (CNS) by specific transport systems...
2016: CNS & Neurological Disorders Drug Targets
Nicole Armbruster, Annalisa Lattanzi, Matthieu Jeavons, Laetitia Van Wittenberghe, Bernard Gjata, Thibaut Marais, Samia Martin, Alban Vignaud, Thomas Voit, Fulvio Mavilio, Martine Barkats, Ana Buj-Bello
Spinal muscular atrophy (SMA) is an autosomal recessive disease of variable severity caused by mutations in the SMN1 gene. Deficiency of the ubiquitous SMN function results in spinal cord α-motor neuron degeneration and proximal muscle weakness. Gene replacement therapy with recombinant adeno-associated viral (AAV) vectors showed therapeutic efficacy in several animal models of SMA. Here, we report a study aimed at analyzing the efficacy and biodistribution of a serotype-9, self-complementary AAV vector expressing a codon-optimized human SMN1 coding sequence (coSMN1) under the control of the constitutive phosphoglycerate kinase (PGK) promoter in neonatal SMNΔ7 mice, a severe animal model of the disease...
2016: Molecular Therapy. Methods & Clinical Development
Theodorus B M Hakvoort, Youji He, Wim Kulik, Jacqueline L M Vermeulen, Suzanne Duijst, Jan M Ruijter, Jurgen H Runge, Nicolaas E P Deutz, S Eleonore Koehler, Wouter H Lamers
: Glutamine synthetase (GS) catalyzes condensation of ammonia with glutamate to glutamine. Glutamine serves, with alanine, as a major nontoxic interorgan ammonia carrier. Elimination of hepatic GS expression in mice causes only mild hyperammonemia and hypoglutaminemia but a pronounced decrease in the whole-body muscle-to-fat ratio with increased myostatin expression in muscle. Using GS-knockout/liver and control mice and stepwise increments of enterally infused ammonia, we show that ∼35% of this ammonia is detoxified by hepatic GS and ∼35% by urea-cycle enzymes, while ∼30% is not cleared by the liver, independent of portal ammonia concentrations ≤2 mmol/L...
September 19, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Julia A G Silveira, Bruna T Silvestre, Camila V Bastos, Múcio F B Ribeiro
The aim of the study was to isolate and establish an Anaplasma marginale strain from Brazilian brown brocket deer, Mazama gouazoubira, in the Ixodes scapularis cell line IDE8. Blood from a free-living adult female M. gouazoubira naturally infected with A. marginale (MGI5) was inoculated intravenously into a splenectomized calf. When A. marginale rickettsemia was 2.5%, blood was collected and cryopreserved in liquid nitrogen with dimethylsulfoxide (DMSO). IDE8 cell cultures were infected with calf blood inoculated with the A...
October 2016: Ticks and Tick-borne Diseases
Maximilian Richter, Kamola Saydaminova, Roma Yumul, Rohini Krishnan, Jing Liu, Eniko-Eva Nagy, Manvendra Singh, Zsuzsanna Izsvák, Roberto Cattaneo, Wolfgang Uckert, Donna Palmer, Philip Ng, Kevin G Haworth, Hans-Peter Kiem, Anja Ehrhardt, Thalia Papayannopoulou, André Lieber
Current protocols for hematopoietic stem/progenitor cell (HSPC) gene therapy, involving the transplantation of ex vivo genetically modified HSPCs are complex and not without risk for the patient. We developed a new approach for in vivo HSPC transduction that does not require myeloablation and transplantation. It involves subcutaneous injections of granulocyte-colony-stimulating factor/AMD3100 to mobilize HSPCs from the bone marrow (BM) into the peripheral blood stream and the IV injection of an integrating, helper-dependent adenovirus (HD-Ad5/35(++)) vector system...
November 3, 2016: Blood
Evan E Joslin, Jan Paulo T Zaragoza, Regina A Baglia, Maxime A Siegler, David P Goldberg
The influence of remote peripheral substitution on the physicochemical properties and reactivity of phosphorus and manganese corrolazine (Cz) complexes was examined. The substitution of p-MeO for p-t-Bu groups on the eight phenyl substituents of the β-carbon atoms of the Cz ring led to changes in UV-vis transitions and redox potentials for each of the complexes. The oxygen atom transfer (OAT) and hydrogen atom transfer (HAT) reactivity of the Mn(V)(O) complexes was also influenced by p-MeO substitution. The OAT reactivity of Mn(V)(O)(MeOP8Cz) (MeOP8Cz = octakis(p-methoxyphenyl)corrolazinato(3-)) with triarylphosphine (PAr3) substrates led to second-order rate constants from 10...
September 6, 2016: Inorganic Chemistry
Brent J Yamamoto, Annette M Shadiack, Sarah Carpenter, Daniel Sanford, Lisa N Henning, Nestor Gonzales, Edward O'Connor, Leslie S Casey, Natalya V Serbina
The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here...
October 2016: Antimicrobial Agents and Chemotherapy
Kirti Gupta, Sahil Mehta, Chirag K Ahuja, Pravin Salunke, Navneet Sharma
Tumefactive demyelinating (TD) lesions are extremely challenging lesions to diagnose during their histopathological examination and are often misdiagnosed as tumors. On the contrary, a glioblastoma multiforme is rarely misdiagnosed as a TD unless the two coexist. We present a case of a 60-year old man who was diagnosed as having tumefactive demyelination on a stereotactic biopsy. At autopsy, however, the lesion revealed a grade IV glioblastoma. The myelin loss along the periphery of the lesion was erroneously interpreted as TD during the histopathological examination...
July 2016: Neurology India
Jun Tanaka, Akira Kitashoji, Yuki Fukunaga, Junichi Kashihara, Atsushi Nakano, Akihito Kamizono
Recurrent pregnancy loss (RPL), which mostly is of unknown etiology (unexplained RPL, uRPL), is defined as three or more consecutive spontaneous abortions. Some women with uRPL display a higher fraction and cytotoxicity of natural killer (NK) cells in the periphery and endometrium. Therefore, some uRPL cases have been explained by autoimmune abnormalities. The efficacy of intravenous immunoglobulin (IVIg) for uRPL has been confirmed in several clinical trials; however, its mechanism remains unknown, mainly because the abortion mechanism remains to be elucidated...
August 2016: Biology of Reproduction
Liang Zhang, Amyn A Habib, Dawen Zhao
Phosphatidylserine (PS), which is normally intracellular, becomes exposed on the outer surface of viable endothelial cells (ECs) of tumor vasculature. Utilizing a PS-targeting antibody, we have recently established a PS-targeted liposomal (PS-L) nanoplatform that has demonstrated to be highly tumor-selective. Because of the vascular lumen-exposed PS that is immediately accessible without a need to penetrate the intact blood brain barrier (BBB), we hypothesize that the systemically administered PS-L binds specifically to tumor vascular ECs, becomes subsequently internalized into the cells and then enables its cargos to be efficiently delivered to glioma parenchyma...
May 25, 2016: Oncotarget
Roger Reidelberger, Alvin Haver, Krista Anders, Bettye Apenteng, Craig Lanio
Glucagon-like peptide-1 (GLP-1), peptide YY (3-36) [PYY(3-36)], amylin, ghrelin, insulin, and leptin are thought to act as hormonal signals from periphery to brain to control food intake. Here, we determined the effects of solid-phase extraction of plasma in measuring these hormones in blood of lean and diet-induced obese rats. Individual enzyme-linked immunoassays and a multiplex assay were used to measure active GLP-1, total PYY, active amylin, active ghrelin, insulin, leptin, and total GIP in response to (1) addition of known amounts of the peptides to lean and obese plasma, (2) a large meal in lean and obese rats, and (3) intravenous infusions of anorexigenic doses of GLP-1, PYY(3-36), amylin, and leptin in lean rats...
May 2016: Physiological Reports
Elisabeth R Mari, Javad Rasouli, Bogoljub Ciric, Jason N Moore, José R Conejo-Garcia, Naveen Rajasagi, Guang-Xian Zhang, Gabriel A Rabinovich, Abdolmohamad Rostami
In experimental autoimmune encephalomyelitis (EAE), intravenous (i.v.) injection of the antigen, myelin oligodendrocyte glycoprotein-derived peptide, MOG35-55 , suppresses disease development, a phenomenon called i.v. tolerance. Galectin-1, an endogenous glycan-binding protein, is upregulated during autoimmune neuroinflammation and plays immunoregulatory roles by inducing tolerogenic dendritic cells (DCs) and IL-10 producing regulatory type 1 T (Tr1) cells. To examine the role of galectin-1 in i.v. tolerance, we administered MOG35-55 -i...
July 2016: European Journal of Immunology
Anton Dvorzhak, Tatyana Vagner, Knut Kirmse, Rosemarie Grantyn
UNLABELLED: This study evaluates single-cell indicators of glutamate transport in sulforhodamine 101-positive astrocytes of Q175 mice, a knock-in model of Huntington's disease (HD). Transport-related fluorescent ratio signals obtained with sodium-binding benzofuran isophtalate (SBFI) AM from unperturbed or voltage-clamped astrocytes and respective glutamate transporter currents (GTCs) were induced by photolytic or synaptic glutamate release and isolated pharmacologically. The HD-induced deficit ranged from -27% (GTC maximum at -100 mV in Ba(2+)) to -41% (sodium transients in astrocytes after loading SBFI-AM)...
May 4, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Theresa M Carbonaro, Michael B Gatch
N,N-dimethyltryptamine (DMT) is an indole alkaloid widely found in plants and animals. It is best known for producing brief and intense psychedelic effects when ingested. Increasing evidence suggests that endogenous DMT plays important roles for a number of processes in the periphery and central nervous system, and may act as a neurotransmitter. This paper reviews the current literature of both the recreational use of DMT and its potential roles as an endogenous neurotransmitter. Pharmacokinetics, mechanisms of action in the periphery and central nervous system, clinical uses and adverse effects are also reviewed...
September 2016: Brain Research Bulletin
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