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https://www.readbyqxmd.com/read/29783755/a-miniaturized-extruder-to-prototype-amorphous-solid-dispersions-selection-of-plasticizers-for-hot-melt-extrusion
#1
Matthias E Lauer, Reto Maurer, Anne T De Paepe, Cordula Stillhart, Laurence Jacob, Rajesh James, Yuki Kojima, Rene Rietmann, Tom Kissling, Joost A van den Ende, Sabine Schwarz, Olaf Grassmann, Susanne Page
Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed...
May 19, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29771981/antimicrobial-activity-of-bovine-nk-lysin-derived-peptides-on-mycoplasma-bovis
#2
Rohana P Dassanayake, Shollie M Falkenberg, Karen B Register, Daniel Samorodnitsky, Eric M Nicholson, Timothy A Reinhardt
Antimicrobial peptides (AMPs) are a diverse group of molecules which play an important role in the innate immune response. Bovine NK-lysins, a type of AMP, have been predominantly found in the granules of cytotoxic T-lymphocytes and NK-cells. Bovine NK-lysin-derived peptides demonstrate antimicrobial activity against various bacterial pathogens, including several involved in bovine respiratory disease complex (BRDC) in cattle; however, such studies are yet to be performed with one important contributor to the BRDC, Mycoplasma bovis...
2018: PloS One
https://www.readbyqxmd.com/read/29767468/central-adenosine-a-1-receptors-inhibit-cough-via-suppression-of-excitatory-glutamatergic-and-tachykininergic-neurotransmission
#3
Ahmed Z El-Hashim, Seena Mathews, Fajer Al-Shamlan
BACKGROUND AND PURPOSE: The A1 adenosine receptor is reported to mediate several excitatory effects in the airways and has inhibitory effects in the central nervous system. In this study, we investigated the role of peripheral and central A1 adenosine receptors in regulating cough and airway obstruction. EXPERIMENTAL APPROACH: Drugs were administered to guinea pigs via the inhaled or intracerebroventricular (i.c.v.) routes. Cough was induced by exposing guinea pigs to aerosolised 0...
May 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29745331/from-the-anti-nociceptive-substance-p-metabolite-substance-p-1-7-to-small-peptidemimetics
#4
Mathias Hallberg, Anja Sandström
Substance P (SP) is associated with pain and inflammatory processes and is released from terminals of specific sensory nerves. This undecapeptide that mediates its effects through the neurokinin type 1 (NK1) receptor, is rapidly degraded in vivo to smaller fragments. The heptapeptide SP(1-7) with a hitherto unknown receptor, is a major bioactive fragment and displays often opposite actions to those induced by SP. Hence, SP(1-7) elicits anti-nociceptive and anti-hyperalgesic effects. These observations have attracted a substantial interest and in this mini-review the efforts to transform the heptapeptide SP(1-7) into more drug-like small-molecule SP(1-7) peptidomimetics as a potential new class of analgesics are summarized...
May 8, 2018: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29730322/salt-formation-improved-the-properties-of-a-candidate-drug-during-early-formulation-development
#5
Kalle Sigfridsson, Matti Ahlqvist, Martin Lindsjö, Stefan Paulsson
The purpose of this study was to investigate if AZD5329, a dual neurokinin NK1/2 receptor antagonist, is a suitable candidate for further development as an oral immediate release (IR) solid dosage form as a final product. The neutral form of AZD5329 has only been isolated as amorphous material. In order to search for a solid material with improved physical and chemical stability and more suitable solid-state properties, a salt screen was performed. Crystalline material of a maleic acid salt and a fumaric acid salt of AZD5329 were obtained...
May 3, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29728445/micturition-and-defecation-elicited-by-lys5-meleu9-nle10-nka-4-10-in-conscious-dogs
#6
Nadia Rupniak, Mary Katofiasc, Alexander Walz, Karl B Thor, Edward C Burgard
Tachykinin NK2 receptor agonists may have potential to alleviate clinical conditions associated with bladder and gastrointestinal under-activity by stimulating contraction of visceral smooth muscle. The ability of [Lys5,MeLeu9,Nle10]-NKA(4-10) (LMN-NKA) to elicit micturition and defecation was examined after repeated administration in groups of 2-10 conscious dogs. Administration of 10-100 μg/kg i.v., 4 times daily for 6 consecutive days, reliably elicited micturition after >90% of doses and defecation after >50% of doses...
May 4, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29718298/genomic-structure-and-tissue-expression-of-the-nk-lysin-gene-family-in-bison
#7
Mi Ok Lee, Lauren Dobson, Brian W Davis, Loren Skow, James Derr, James E Womack
Antimicrobial peptides (AMPs) are a class of natural peptides with varying numbers of amino acids. They are principal components of innate immunity in vertebrates, encoding natural antibiotics and providing a protective response against a broad range of microbes including those responsible for tuberculosis, an important disease in bison. NK-lysins are AMPs that have been described in various organisms and are coded by a single gene in several mammalian species, including human. Recently, we described a family of four NK-lysin genes in cattle...
April 28, 2018: Journal of Heredity
https://www.readbyqxmd.com/read/29702501/the-latest-consensus-on-antiemetics
#8
Jørn Herrstedt
PURPOSE OF REVIEW: The present review summarizes and discuss the most recent updated antiemetic consensus. RECENT FINDINGS: Two new neurokinin (NK)1-receptor antagonists, netupitant and rolapitant, have been approved by the Food and Drug Administration and the European Medicines Agency and incorporated in the latest versions of the MASCC/ESMO, ASCO, and NCCN guidelines. Guidelines all recommend a combination of a serotonin (5-HT)3-receptor antagonist, dexametha-sone, and a NK1-receptor antagonist in patients receiving highly emetogenic chemotherapy (HEC) with the addition of the multireceptor targeting agent, olanzapine, as an option in cisplatin or anthracycline-cyclophosphamide chemotherapy...
April 26, 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29701165/flow-cytometric-analysis-of-pro-inflammatory-cytokine-production-in-hyperglycemic-mouse-model
#9
Muhaimin Rifa I, Mulya Dwi Wahyuningsih, Noviana Dwi Lestari, Aris Soewondo, Mansur Ibrahim, Hideo Tsuboi
OBJECTIVE: The sharp increase of pro-inflammatory cytokine becomes a severe problem in some degenerative diseases. This study aimed to investigate the effect of cherry leaf extract (CLE) on pro-inflammatory cytokine production in a hyperglycaemic mouse model. METHODS: In this study, we induced hyperglycemia with high-fat diet and 20% fructose drink. Hyperglycemic mice were orally administered with CLE with the dose of 420, 700, and 28000 mg/kg BW for two weeks. After treatment, the pro-inflammatory molecule was analyzed by flow cytometry by isolating spleen cells...
April 26, 2018: Recent Patents on Food, Nutrition & Agriculture
https://www.readbyqxmd.com/read/29667586/drug-drug-interactions-with-aprepitant-in-antiemetic-prophylaxis-for-chemotherapy
#10
R Schoffelen, A G Lankheet, C M L van Herpen, J J M van der Hoeven, I M E Desar, C Kramers
In the current guidelines to prevent hemotherapyinduced nausea and vomiting, multiple antiemetic drugs are administered simultaneously. In patients who receive highly emetogenic chemotherapy, aprepitant, an NK1-receptor antagonist, is combined with ondansetron and dexamethasone. Aprepitant can influence the pharmacokinetics of other drugs, as it is an inhibitor and inducer of CYP3A4. Some anticancer drugs and other co-medication frequently used in cancer patients are CYP3A4 or CYP29C substrates. We give an overview of the metabolism and current data on clinically relevant drug-drug interactions with aprepitant during chemotherapy...
April 2018: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/29650945/impact-of-regulatory-t-cells-on-innate-immune-cells-in-a-pre-sensitized-heart-transplant-model
#11
Weihua Gong, Baoqing Liu, Juntao Chen, Chen Liu, Zhonghua Shen
BACKGROUND Although our previous studies revealed the role of Tregs (regulatory T cells) and MDSCs (myeloid-derived suppressor cells) in a pre-sensitized cardiac transplant model, interplay between Tregs and NK cells, neutrophils, and macrophages remain undefined. MATERIAL AND METHODS Mice heart transplantation with skin pre-sensitization was performed, in which prolonged-cold ischemia time (PCI) was used for donor treatment. Syngeneic heterotopic heart transplant recipients with PCI were treated with PC61 (monoclonal anti-CD25 antibodies), adoptive cell transfer with Tregs, and rapamycin...
April 13, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29611298/in-vitro-evaluation-of-225-ac-dota-substance-p-for-targeted-alpha-therapy-of-glioblastoma-multiforme
#12
Agnieszka Majkowska-Pilip, Maria Rius, Frank Bruchertseifer, Christos Apostolidis, Mirjam Weis, Milton Bonelli, Marta Laurenza, Leszek Królicki, Alfred Morgenstern
Glioblastoma multiforme (GBM) is the most malignant form of brain tumors with dismal prognosis despite treatment by surgery combined with radiotherapy and chemotherapy. The neuropeptide Substance P (SP) is the physiological ligand of the neurokinin-1 receptor (NK1-R), which is highly expressed in glioblastoma cells. Thus, SP represents a potential ligand for targeted alpha therapy. In this study, a protocol for the synthesis of SP labelled with the alpha emitter225 Ac was developed and binding affinity properties were determined...
April 2, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29576738/functionalized-tio-2-nanoparticles-labelled-with-225-ac-for-targeted-alpha-radionuclide-therapy
#13
Edyta Cędrowska, Marek Pruszynski, Agnieszka Majkowska-Pilip, Sylwia Męczyńska-Wielgosz, Frank Bruchertseifer, Alfred Morgenstern, Aleksander Bilewicz
The225 Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with225 Ac is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-targeted tissues. In the present work, we propose to apply TiO2 nanoparticles (NPs) as carrier for225 Ac and its decay products. The surface of TiO2 nanoparticles with 25 nm diameter was modified with Substance P (5-11), a peptide fragment which targets NK1 receptors on the glioma cells, through the silan-PEG-NHS linker...
2018: Journal of Nanoparticle Research: An Interdisciplinary Forum for Nanoscale Science and Technology
https://www.readbyqxmd.com/read/29575692/effect-of-the-in-vivo-application-of-granulocyte-colony-stimulating-factor-on-nk-cells-in-bone-marrow-and-peripheral-blood
#14
Xing-Xing Yu, Ting-Ting Han, Ling-Ling Xu, Ying-Jun Chang, Xiao-Jun Huang, Xiang-Yu Zhao
Granulocyte colony-stimulating factor (G-CSF) has been widely used in the field of allogeneic haematopoietic stem cell transplantation (allo-HSCT) for priming donor stem cells from the bone marrow (BM) to peripheral blood (PB) to collect stem cells more conveniently. Donor-derived natural killer (NK) cells have important antitumour functions and immune regulatory roles post-allo-HSCT. The aim of this study was to evaluate the effect of G-CSF on donors' NK cells in BM and PB. The percentage of NK cells among nuclear cells and lymphocyte was significantly decreased and led to increased ratio of T and NK cells in BM and PB post-G-CSF in vivo application...
March 25, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29572051/botulinum-toxin-type-a-and-gabapentin-attenuate-postoperative-pain-and-nk1-receptor-internalization-in-rats
#15
Xueyang Li, Ruijuan Guo, Yuqing Sun, Huili Li, Danxu Ma, Chen Zhang, Yun Guan, Junfa Li, Yun Wang
Treatment of postoperative pain remains a challenge in clinic. Botulinum toxin type A (BoNT/A) and gabapentin regulate the release of neurotransmitters from primary afferent neurons, but their effects of on postoperative pain are not clear. In the current study, using pain behavioral tests, Western blot analysis, and immunocytochemistry, we examined whether BoNT/A, alone or in combination with intrathecal gabapentin, inhibited pain hypersensitivity and attenuated the increase in neurokinin 1 (NK1) receptor internalization in dorsal horn neurons after plantar incision...
March 20, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29570822/type-1-innate-lymphoid-cell-aggravation-of-atherosclerosis-is-mediated-through-tlr4
#16
Chun Wu, Shaolin He, Jie Liu, Boyuan Wang, Jibin Lin, Yanping Duan, Xiaonan Gao, Dazhu Li
ILC populations elaborate a similar cytokine expression pattern with helper T cell subsets Th1, Th2 and Th17. Recent studies indicate that CD25+ILC2 could alleviate atherosclerosis by altering lipid metabolism, whereas the depletion of CD90-expressing ILCs had no influence on atherosclerosis. Thus, these findings raise the question on whether ILC1 cells react on atherosclerosis. Hence, our group attempted to explore the role of ILC1 cells in atherosclerosis. We found that ILC1 cells have a high Th1-like gene expression of T-bet and IFN-γ, which is distinct from ILC2, ILC3, or conventional NK (cNK) cells...
March 23, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29547608/cisplatin-based-therapy-and-cinv-optimal-antiemetics-during-germ-cell-testicular-cancer-treatment
#17
Meghan Mastrangelo
BACKGROUND: Cisplatin-based chemotherapy regimens are the backbone of chemotherapy for germ cell testicular cancer. Cisplatin is administered for five days, causing an overlap of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Although CINV is widely researched, studies involving multiday chemotherapy regimens are limited. OBJECTIVES: This article synthesizes the research in antiemetics used in multiday cisplatin-based chemotherapy regimens and provides recommendations to optimize antiemetic therapy...
April 1, 2018: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29541991/rapid-reconstitution-of-nk1-cells-after-allogeneic-transplantation-is-associated-with-a-reduced-incidence-of-graft-versus-host-disease
#18
Xingxing Yu, Lingling Xu, Yingjun Chang, Xiaojun Huang, Xiangyu Zhao
The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Th1, Th2, Th3 and Tr1 cells. Here, we investigate levels of type 1 (IFN-gamma; NK1), type 2 (IL-13; NK2), type 3 (TGF-beta; NK3) and regulatory (IL-10; NKr) cytokines in peripheral blood to assess the cytokine profiles of natural killer (NK) cells following human allogeneic hematopoietic stem cell transplantation (allo-HSCT). NK2 and NK3 cell expansion was observed after allo-HSCT; levels of NKr cells reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT...
March 9, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29533981/nano-pulse-stimulation-ablates-orthotopic-rat-hepatocellular-carcinoma-and-induces-innate-and-adaptive-memory-immune-mechanisms-that-prevent-recurrence
#19
Brittany P Lassiter, Siqi Guo, Stephen J Beebe
Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver...
March 13, 2018: Cancers
https://www.readbyqxmd.com/read/29533658/interrogation-of-benzomalvin-biosynthesis-using-fungal-artificial-chromosomes-with-metabolomic-scoring-fac-ms-discovery-of-a-benzodiazepine-synthase-activity
#20
Kenneth D Clevenger, Rosa Ye, Jin Woo Bok, Paul M Thomas, Md Nurul Islam, Galen P Miley, Matthew T Robey, Cynthia Chen, KaHoua Yang, Michael Swyers, Edward Wu, Peng Gao, Chengcang C Wu, Nancy P Keller, Neil L Kelleher
The benzodiazepine benzomalvin A/D is a fungally derived specialized metabolite and inhibitor of the substance P receptor NK1, biosynthesized by a three-gene nonribosomal peptide synthetase cluster. Here, we utilize fungal artificial chromosomes with metabolomic scoring (FAC-MS) to perform molecular genetic pathway dissection and targeted metabolomics analysis to assign the in vivo role of each domain in the benzomalvin biosynthetic pathway. The use of FAC-MS identified the terminal cyclizing condensation domain as BenY-CT and the internal C-domains as BenZ-C1 and BenZ-C2 ...
March 20, 2018: Biochemistry
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