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Peripherial iv

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 blood-spinal 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...
September 20, 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 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-KO/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 G-CSF/AMD3100 to mobilize HSPCs from the bone marrow into the peripheral blood stream and the intravenous injection of an integrating, helper-dependent adenovirus (HD-Ad5/35++) vector system...
August 23, 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
Jung Woo Chang, Jang Hyun Lee, Matthew Seung Suk Choi
Despite numerous therapeutic advances, the treatment of pressure sores remains a challenge. The increased use of perforator flaps enables surgeons to minimize donor-site morbidity by sparing the underlying muscle. In the presence of focal deep spaces, however, the inclusion of muscle would be beneficial. The goal of this study was to introduce a method for including a muscle patch at the periphery of a perforator-based island flap for coverage of sacral pressure sores. Between March 2010 and February 2015, 26 patients with stage IV sacral sores underwent perforator-based island flap reconstruction with a peripheral muscle patch...
June 2016: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
Niamh Conlon, Navid Sadri, Adriana D Corben, Lee K Tan
Acinic cell carcinoma of breast is a rare subtype of triple-negative breast carcinoma and demonstrates extensive morphologic overlap with acinic cell carcinoma of the salivary gland. In this study, we perform a detailed morphologic and immunohistochemical description of 2 cases of this rare entity and undertake a comprehensive review of all reported cases of breast acinic cell carcinoma in the English language literature to date. One-third of reported cases of breast acinic cell carcinoma have been associated with the presence of a ductal carcinoma not otherwise specified component, which is frequently poorly differentiated...
May 2016: Human Pathology
Swapneeta S Date, Cheng-Yen Charles Chen, Yidong Chen, Michaela Jansen
The proton-coupled folate transporter (PCFT, SLC46A1) transports folic acid across the plasma membrane, together with an excess of protons such that the net charge translocation is positive. We developed 3D structural models of PCFT threaded onto the X-ray structures of major facilitator superfamily (MFS) members that were identified as close structural homologues. The model of PCFT threaded onto the glycerol-3-phosphate transporter (GlpT) structure is consistent with detailed accessibility studies in the absence of extracellular substrate and at pH 7...
March 2016: FEBS Open Bio
Laura L Hocum Stone, Feng Xiao, Jessica Rotschafer, Zhenhong Nan, Mario Juliano, Cyndy D Sanberg, Paul R Sanberg, Nicole Kuzmin-Nichols, Andrew Grande, Maxim C-J Cheeran, Walter C Low
Despite the high prevalence and devastating outcome, there remain a few options for treatment of ischemic stroke. Currently available treatments are limited by a short time window for treatment and marginal efficacy when used. We have tested a human umbilical cord blood-derived stem cell line that has been shown to result in a significant reduction in stroke infarct volume as well as improved functional recovery following stroke in the rat. In the present study we address the mechanism of action and compared the therapeutic efficacy of high- versus low-passage nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs)...
2016: Cell Transplantation
Tobias Ruck, Ali Maisam Afzali, Karl-Friedrich Lukat, Maria Eveslage, Catharina C Gross, Steffen Pfeuffer, Stefan Bittner, Luisa Klotz, Nico Melzer, Heinz Wiendl, Sven G Meuth
BACKGROUND: Alemtuzumab (Lemtrada®) is a newly approved therapeutic agent for relapsing-remitting multiple sclerosis (RRMS). In previous phase II and III clinical trials, alemtuzumab has proven superior efficacy to subcutaneous interferon beta-1a concerning relapse rate and disability progression with unprecedented durability and long-lasting freedom of disease activity. The humanized monoclonal antibody targets CD52, leading to a rapid and long-lasting depletion, especially of B and T cells...
2016: BMC Neurology
James A Pearson, Terri C Thayer, James E McLaren, Kristin Ladell, Evy De Leenheer, Amy Phillips, Joanne Davies, Dimitri Kakabadse, Kelly Miners, Peter Morgan, Li Wen, David A Price, F Susan Wong
NOD mice, a model strain for human type 1 diabetes, express proinsulin (PI) in the thymus. However, insulin-reactive T cells escape negative selection, and subsequent activation of the CD8(+) T-cell clonotype G9C8, which recognizes insulin B15-23 via an αβ T-cell receptor (TCR) incorporating TRAV8-1/TRAJ9 and TRBV19/TRBJ2-3 gene rearrangements, contributes to the development of diabetes. In this study, we used fixed TRAV8-1/TRAJ9 TCRα-chain transgenic mice to assess the impact of PI isoform expression on the insulin-reactive CD8(+) T-cell repertoire...
June 2016: Diabetes
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