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Ekkehard Grünig, Nicola Benjamin, Tobias J Lange, Ulrich Krueger, Hans Klose, Claus Neurohr, Heinrike Wilkens, Michael Halank, Hans-Jürgen Seyfarth, Matthias Held, Andrew Traube, Michelle Pernow, E Robert Grover, Benjamin Egenlauf, Felix Gerhardt, Thomas Viethen, Stephan Rosenkranz
BACKGROUND: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. OBJECTIVES: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. METHODS: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study...
October 27, 2016: Respiration; International Review of Thoracic Diseases
Chunxiang Feng, Jinqian Hu, Chang Liu, Shiliang Liu, Guiying Liao, Linjie Song, Xiaoyong Zeng
The increased incidence of stress urinary incontinence (SUI) in postmenopausal women has been proposed to be associated with a reduction in the level of 17-β estradiol (E2). E2 has also been shown to enhance the multi-differentiation ability of adipose-derived stem cells (ASCs) in vitro. However, studies on the potential value of E2 for tissue engineering in SUI treatment are rare. In the present study, we successfully fabricated myogenically differentiated ASCs (MD-ASCs), which were seeded onto a Poly(l-lactide)/Poly(e-caprolactone) electrospinning nano-scaffold, and incorporated E2 into the system, with the aim of improving the proliferation and myogenic differentiation of ASCs...
2016: PloS One
Aurelie Thomas, Amy Miller, Johnny Roughan, Aneesa Malik, Katherine Haylor, Charlotte Sandersen, Paul Flecknell, Matthew Leach
Concerns over interactions between analgesics and experimental outcomes are a major reason for withholding opioids from rats undergoing surgical procedures. Only a fraction of morphine injected intravenously reaches receptors responsible for analgesia in the central nervous system. Intrathecal administration of morphine may represent a way to provide rats with analgesia while minimizing the amount of morphine injected. This study aimed to assess whether morphine injected intrathecally via direct lumbar puncture provides sufficient analgesia to rats exposed to acute surgical pain (caudal laparotomy)...
2016: PloS One
Xin Chen, Zelan Ma, Yanqi Huang, Lan He, Cuishan Liang, Changzheng Shi, Zhongping Zhang, Changhong Liang, Zaiyi Liu
PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) for monitoring the ultra-early (within 24 hours) treatment effect of sorafenib in human hepatocellular carcinoma (HCC) xenografts. MATERIALS AND METHODS: With institutional Animal Care and Use Committee approval, 16 BALB/c nude mice bearing subcutaneous HCC xenografts underwent serial Gaussian and non-Gaussian DWI at baseline and 1, 3, 6, 12, and 24 hours posttreatment using a 1...
October 26, 2016: Journal of Magnetic Resonance Imaging: JMRI
Jun Watanabe, Mitsuyoshi Ota, Makoto Kawamoto, Yago Akikazu, Yusuke Suwa, Hirokazu Suwa, Masashi Momiyama, Atsushi Ishibe, Kazuteru Watanabe, Hidenobu Masui, Kaoru Nagahori
BACKGROUND: The effects of subcutaneous closed-suction Blake drain for preventing incisional surgical site infections (SSIs) after colorectal surgery have never been evaluated in a randomized controlled trial (RCT). Thus, we performed a RCT to evaluate the clinical benefits of using a subcutaneous closed-suction Blake drain in patients undergoing colorectal surgery. METHOD: Consecutive patients who underwent colorectal surgery were enrolled in this study. Patients were randomly assigned to the subcutaneous closed-suction drainage arm or the control (no subcutaneous drainage) arm...
October 25, 2016: International Journal of Colorectal Disease
Paolo Lissoni
Despite its apparent failure in cancer therapy, IL-2 still remains fundamental in the activation of antitumor immunity. Areas covered: The aim of this review is the reinterpretation of the role of IL-2 in anticancer immunity, according to knowledge gained of the cytokine network, by highlighting its importance in inducing T helper-1 (TH1) cell proliferation, natural killer (NK) actHivation and IL-12 secretion. However, its main negative effect is the stimulation of regulatory T cells (Tregs), which in contrast suppresses anticancer immunity...
October 26, 2016: Expert Review of Clinical Immunology
Gabriela Berg, Verónica Miksztowicz, Celina Morales, Magalí Barchuk, Graciela López, Ricardo Póveda, Ricardo Gelpi, Laura Schreier, Miguel Rubio
BACKGROUND: Epicardial adipose tissue (EAT) is a visceral adipose tissue (AT) surrounding and infiltrating myocardium and coronary arteries. Increased EAT may represent a chronic inflammatory injury and represent a link with coronary artery disease (CAD). Metalloproteinases (MMPs) are involved in expansion of AT. OBJECTIVE: to evaluate MMP-2 and -9 behavior in EAT from coronary artery disease patients. METHODS: In EAT and subcutaneous AT (SAT) from patients undergoing coronary artery bypass graft (CABG, n=30) or valve replacement (No CABG, n=18), MMP-2 and -9 activity and localization, inflammatory cells and vascular endothelial growth factor (VEGF) levels were determined...
October 24, 2016: Current Vascular Pharmacology
Srinivas M Naren Satya, Kamala Retnam Mayilvaganan, V N Amogh, B V Balakrishna, Munnangi Satya Gautam, Ivvala Sai Prathyusha
BACKGROUND: Cysticercosis is a parasitic infection caused by the larval stages of the pork tapeworm, Taenia solium. The subcutaneous form of the disease is a relatively rare clinical entity. Despite its rarity, it is imperative for a radiologist to be aware of this subcutaneous form of the disease and its various radiological patterns while evaluating any subcutaneous swelling. In this paper, we aimed to describe a typical case of 'subcutaneous cysticercosis involving the left anterior chest wall' with high resolution ultrasound findings...
2016: Polish Journal of Radiology
John Garcia, Claire Mennan, Helen S McCarthy, Sally Roberts, James B Richardson, Karina T Wright
Autologous chondrocyte implantation (ACI) is a cell-based therapy that has been used clinically for over 20 years to treat cartilage injuries more efficiently in order to negate or delay the need for joint replacement surgery. In this time, very little has changed in the ACI procedure, but now many centres are considering or using alternative cell sources for cartilage repair, in particular mesenchymal stem cells (MSCs). In this study, we have tested the chondrogenic potential of donor-matched MSCs derived from bone marrow (BM), infrapatellar fat pad (FP), and subcutaneous fat (SCF), compared to chondrocytes...
2016: Stem Cells International
Annalisa Ciabattini, Elena Pettini, Fabio Fiorino, Gabiria Pastore, Peter Andersen, Gianni Pozzi, Donata Medaglini
Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Here early biomarkers of adjuvanticity after primary immunization were investigated using four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4(+) T cell and B cell responses was assessed within draining lymph nodes, blood, and spleen, 7 and 12 days after priming...
2016: Frontiers in Immunology
J Chen, Y Liu, S Lu, L Yin, C Zong, S Cui, D Qin, Y Yang, Q Guan, X Li, X Wang
BACKGROUND: Obesity is a risk factor for metabolic diseases, while preadipocyte differentiation or adipogenesis is closely related to obesity occurrence. Long noncoding RNAs (lncRNAs) are a unique class of transcripts in regulation of a variety of biological processes. Using cDNA microarray, we found lncRNA U90926 is negatively correlated with 3T3-L1 preadipocyte differentiation. OBJECTIVE: The aim of this study was to explore the role of lncRNA U90926 (lnc-U90926) in adipogenesis and the underlying mechanisms...
October 26, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
István Kenessey, Krisztina Kói, Orsolya Horváth, Mihály Cserepes, Dávid Molnár, Vera Izsák, Judit Dobos, Balázs HegedÅ S, József Tóvári, József Tímár
BACKGROUND: In non-small cell lung cancer (NSCLC) KRAS-mutant status is a negative prognostic and predictive factor. Nitrogen-containing bisphosphonates inhibit prenylation of small G-proteins (e.g. Ras, Rac, Rho) and thus may affect proliferation and migration. In our preclinical work, we investigated the effect of an aminobisphosphonate compound (zoledronic acid) on mutant and wild type KRAS-expressing human NSCLC cell lines. RESULTS: We confirmed that zoledronic acid was unable to inhibit the prenylation of mutant K-Ras unlike in the case of wild type K-Ras...
October 21, 2016: Oncotarget
Kavin Fatehchand, Elizabeth L McMichael, Brenda F Reader, Huiqing Fang, Ramasamy Santhanam, Shalini Gautam, Saranya Elavazhagan, Payal Mehta, Nathaniel J Buteyn, Giovanna Merchand-Reyes, Sumithira Vasu, Xiaokui Mo, Don M Benson, James S Blachly, William E Carson, John C Byrd, Jonathan P Butchar, Susheela Tridandapani
Acute Myeloid Leukemia (AML) is characterized by the proliferation of immature myeloid-lineage blasts. Due to its heterogeneity and to the high rate of acquired drug resistance and relapse, new treatment strategies are needed. Here, we demonstrate that IFNγ promotes AML blasts to act as effector cells within the context of antibody therapy. Treatment with IFNγ drove AML blasts toward a more differentiated state, wherein they showed increased expression of the M1-related markers HLA-DR and CD86, as well as of FcγRI, which mediates effector responses to therapeutic antibodies...
October 25, 2016: Journal of Biological Chemistry
Sen Zhang, Rana Anjum, Rachel Squillace, Sara Nadworny, Tianjun Zhou, Jeff Keats, Yaoyu Ning, Scott D Wardwell, David Miller, Youngchul Song, Lindsey Eichinger, Lauren Moran, Wei-Sheng Huang, Shuangying Liu, Dong Zou, Yihan Wang, Qurish Mohemmad, Hyun Gyung Jang, Emily Ye, Narayana Narasimhan, Frank Wang, Juan Miret, Xiaotian Zhu, Tim Clackson, David Dalgarno, William C Shakespeare, Victor M Rivera
PURPOSE: Non-small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK(+)) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain. Mutations that confer resistance to second-generation ALK TKIs ceritinib and alectinib have also been identified. Here, we report the structure and first comprehensive preclinical evaluation of the next-generation ALK TKI brigatinib...
October 25, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
A Ghassemi, S S Ahmed, H Ghanepur, A Modabber
The reconstruction of a full-thickness defect of the distal third of the nose requires the restoration of all three anatomical layers. A practical method for three-layer reconstruction of the lower third of the nose and the long-term results of this technique are presented herein. A combined reconstruction technique was utilized, including a reverse subcutaneous pedicled nasolabial flap to restore the nasal mucosa, an auricular cartilage graft for structural support, and a forehead flap for cutaneous coverage of the defect...
October 22, 2016: International Journal of Oral and Maxillofacial Surgery
Brianna L Skinner, Crystal H Johnson, Shannon H Lacy
A 10-y-old pigtail macaque presented with a subcutaneous, soft-tissue mass overlying the right stifle joint. Here we describe the clinical case and histopathologic and immunohistochemical analysis of this lesion. This case represents the first published report of juxtaarticular myxoma in a pigtail macaque.
2016: Comparative Medicine
Chun-Hao Li, Sa-Hoe Lim, Hyang-Hwa Ryu, Kyung-Sub Moon, Tae-Young Jung, Shin Jung
Stereotactic radiosurgery has been recognized as an effective treatment approach for metastatic brain tumors. By increasing the sensitivity of the tumor to radiation and decreasing the marginal dose, it is possible to improve therapeutic efficacy and decrease side-effects. In radiation-induced cells, c-Jun N-terminal kinase (JNK) signaling mediates the phosphorylation of H2AX, which indicates DNA damage sensitivity and modulates the effect of radiation. Lewis lung cancer (LLC) and breast cancer (4T1) cells were irradiated with a Gamma Knife in cell culture tubes...
October 25, 2016: Oncology Reports
E Ilett, T Kottke, J Thompson, K Rajani, S Zaidi, L Evgin, M Coffey, C Ralph, R Diaz, H Pandha, K Harrington, P Selby, R Bram, A Melcher, R Vile
The anti-tumor effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms which depends both on the type of virus and the route of delivery. Here, we show that intra-tumoral (i.t.) oncolysis by Reovirus induced the priming of a CD8+, Th1-type anti-tumor response. In contrast, systemically delivered VSV expressing a cDNA library of melanoma antigens (VSV-ASMEL) promoted a potent anti-tumor CD4+ Th17 response. Therefore, we hypothesised that combining the Reovirus-induced CD8+ T cell response, with the VSV-ASMEL CD4+ Th17 helper response, would produce enhanced anti-tumor activity...
October 25, 2016: Gene Therapy
Kyung Chul Oh, Woojin Hwang, Young Bum Park, Jae Hoon Lee, Hong Seok Moon, Jee Hwan Kim
OBJECTIVE: To determine the effects of alendronate on bone remodeling around osseointegrated implants in rats. MATERIALS AND METHODS: The maxillary first molars were extracted from 36 male Sprague-Dawley rats, and replaced with customized implants. They were then administered twice-weekly subcutaneous injections of either alendronate (alendronate group) or saline (control group) after allowing a 4-week period for osseointegration. They were killed at 4, 8, or 12 weeks after the commencement of the injection protocol, and the implant sites were evaluated comprehensively by microcomputed tomographic, histologic, and biochemical assessments...
October 20, 2016: Implant Dentistry
L Balazova, K Krskova, M Suski, V Sisovsky, N Hlavacova, R Olszanecki, D Jezova, S Zorad
Increasing evidence indicates a role of oxytocin in controlling energy metabolism. The aim of his study was to investigate oxytocin effects on obese phenotype in leptin-resistant Zucker fatty rats, focusing on glucose and lipid metabolism. Zucker fatty rats and their lean controls were treated with oxytocin (3.6 μg/100g body weight/day) by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hours intraperitoneal glucose tolerance test was performed in fasting rats. Oxytocin decreased food intake in both phenotypes while body weight gain reduced only in obese animals...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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