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therapeutic relationship

Matthew Collin, Venetia Bigley
The maintenance of monocytes, macrophages, and dendritic cells (DCs) involves manifold pathways of ontogeny and homeostasis that have been the subject of intense study in recent years. The concept of a peripheral mononuclear phagocyte system continually renewed by blood-borne monocytes has been modified to include specialized DC pathways of development that do not involve monocytes, and longevity through self-renewal of tissue macrophages. The study of development remains difficult owing to the plasticity of phenotypes and misconceptions about the fundamental structure of hematopoiesis...
October 2016: Microbiology Spectrum
Teresa T Vo, Sheeba Varghese Gupta
For treatment-naïve patients with human immunodeficiency virus infection, efavirenz (EFV) together with tenofovir and emtricitabine were once widely prescribed given its efficacy and ease of administration in a combination pill. However, the high rate of central nervous system toxicities from EFV prompted the United States Department of Health and Human Services to move the EFV-based regimen from the recommended to the alternative category. For patients who do meet the criteria for newer recommended antiretroviral treatments, EFV is a viable option and is often the mainstay of treatment outside the United States, as newer antiretroviral treatments are more expensive...
October 25, 2016: Pharmacotherapy
Xiaodong Lai, Yanchun Guo, Zhitao Guo, Ruibao Liu, Xunguo Wang, Fang Wang
miR‑574‑5p has been reported involved in the pathogenesis of numerous human malignancies such as colorectal and lung cancer. In this study, we aimed to explore the roles of REL and miR‑574 in the recurrence of prostate cancer (PCa) and to identify the underlying molecular mechanisms. Our literature search found that miR‑574 is regulated in cancer stem cells (CSCs), and next we used the microRNA (miRNA) database ( to find REL as a target of miR‑574. Luciferase assay was performed to verify the miRNA/target relationship...
October 24, 2016: Oncology Reports
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
Jennifer A Ward, Lauren McLellan, Martin Stockley, Karl R Gibson, Gavin A Whitlock, Charlotte Knights, Jeanine A Harrigan, Xavier Jacq, Edward W Tate
Deubiquitinating enzymes play an important role in a plethora of therapeutically relevant processes, and are emerging as pioneering drug targets. Herein, we present a novel probe Ubiquitin Specific Protease (USP) inhibitor, alongside an alkyne-tagged activity-based probe analogue. Activity-based proteome profiling identified 12 USPs, including USP4, USP16, and USP33, as inhibitor targets using sub-micromolar probe concentrations. This represents the first intact cell activity-based profiling of deubiquitinating enzymes...
October 25, 2016: ACS Chemical Biology
S A Harrison, S R Marri, N Chalasani, R Kohli, W Aronstein, G A Thompson, W Irish, M V Miles, S A Xanthakos, E Lawitz, M Noureddin, T D Schiano, M Siddiqui, A Sanyal, B A Neuschwander-Tetri, P G Traber
BACKGROUND: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. AIM: To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis...
October 24, 2016: Alimentary Pharmacology & Therapeutics
Li-Li Ji, Meng-Wei Guo, Xiu-Jun Ren, Dong-Yu Ge, Gen-Mao Li, Ya Tu
OBJECTIVE: To investigate the effect of electroacupuncture (EA) treatment on the expression of cyclooxygenase (COX) 2 and microglia in spinal cord by using rat model of neuropathic pain, and to probe into the relationship between COX 2 and microglia. METHODS: The rats were randomly divided into 6 groups, including normal control group, model group, sham group, EA 1 group (distant acupoints + local acupoints), EA 2 group (local acupoints), and EA 3 group (distant acupoints)...
October 24, 2016: Chinese Journal of Integrative Medicine
F Sörgel, R Höhl, R Glaser, C Stelzer, M Munz, M Vormittag, M Kinzig, J Bulitta, C Landersdorfer, A Junger, M Christ, M Wilhelm, U Holzgrabe
Optimized dosage regimens of antibiotics have remained obscure since their introduction. During the last two decades pharmacokinetic(PK)-pharmacodynamic(PD) relationships, originally established in animal experiments, have been increasingly used in patients. The action of betalactams is believed to be governed by the time the plasma concentration is above the minimum inhibitory concentration (MIC). Aminoglycosides act as planned when the peak concentration is a multiple of the MIC and vancomycin seems to work best when the area under the plasma vs...
October 24, 2016: Medizinische Klinik, Intensivmedizin und Notfallmedizin
M A Sotomayor-Sobrino, A Ochoa-Aguilar, L A Méndez-Cuesta, C Gómez-Acevedo
INTRODUCTION: Stroke is one of the leading causes of death in the world; its incidence is increasing due to increased life expectancy. However, treatment options for these patients are limited since no clinically effective drugs have been developed to date. DEVELOPMENT: According to clinical evidence, a number of neurochemical changes take place after stroke, including energy depletion, increased free radical synthesis, calcium accumulation, neurotransmitter imbalance, excitotoxicity, and, at a later stage, immune system activation leading to inflammation...
October 21, 2016: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Peng Wang, Jianrui Li, Qiang Diao, YuanKai Lin, Jun Zhang, Lin Li, Gang Yang, Xiaokun Fang, Xie Li, YingQi Chen, Ling Zheng, Guangming Lu
BACKGROUND: Gliomas are the most common primary brain tumors in adults, in some cases, radiotherapy may be the preferred treatment option especially for elderly people who cannot endure surgery. Therefore, it is necessary to evaluate the effects of radiotherapy on glioma. Arterial spin labeling (ASL) is an MR imaging technique that allows for a quantitative determination of cerebral blood flow (CBF) noninvasively. Tumor volume is still an important determinant for evaluating treatment response...
November 2016: European Journal of Radiology
Ute Blassmann, Anka C Roehr, Otto R Frey, Cornelia Vetter-Kerkhoff, Niklas Thon, William Hope, Josef Briegel, Volker Huge
BACKGROUND: Ventriculitis is a complication of temporary intraventricular drains. The limited penetration of meropenem into the cerebrospinal fluid (CSF) is well known. However, ventricular CSF pharmacokinetic data in patients with ventriculitis are lacking. The aim of this study was to evaluate meropenem pharmacokinetics in the serum and CSF of neurocritical care patients with proven or suspected ventriculitis. METHODS: We conducted an observational pharmacokinetic study of neurocritical care patients with proven or suspected ventriculitis receiving meropenem...
October 24, 2016: Critical Care: the Official Journal of the Critical Care Forum
Justin Ernat, Christine Ho, Robert L Wimberly, ChanHee Jo, Anthony I Riccio
BACKGROUND: Few studies have prospectively assessed functional outcomes after the surgical management of supracondylar humerus fractures (SCHFXs) and the relationship between fracture pattern and ultimate patient outcome has never been prospectively evaluated. The purpose of this study was to prospectively evaluate fracture classification and functional outcome in children with extension SCHFXs using validated outcome measures. METHODS: An Institutional Review Board-approved prospective enrollment of consecutive patients with operative SCHFX was performed over a 3-year period...
October 21, 2016: Journal of Pediatric Orthopedics
L-Z Qin, W Li, Y Huang, F Lu, S-J Li, H-Q Yang, J-W Zhang
OBJECTIVE: This study aims to investigate the expression of pentraxin3 (PTX3) in elderly patients with acute cerebral infarction (ACI) and to analyze the relationship of PTX3 with the severity and prognosis of ACI. PATIENTS AND METHODS: Between June 2014 and August 2015, 96 elderly patients with first-onset of ACI admitted to our institution were enrolled in the present study. Also, 70 healthy elderly subjects were included as controls in this study. Levels of PTX3, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homocysteine (Hcy), fibrinogen (FIB), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined in all patients both pre-therapeutically and 30 days post-therapeutically...
October 2016: European Review for Medical and Pharmacological Sciences
V N Sukhorukov, V P Karagodin, E R Zakiev, A N Orekhov
This review mainly focuses on the medical and biological role of relatively poor studied enzymes known as sialidases. Structure and function of sialic acid, particularly as a component of gangliosides and plasma lipoproteins is described. Among the whole variety of sialidases, trans-sialidase is of special interest, since it is capable of removing sialic acid from the low density lipoprotein (LDL) particles and transferring it to different acceptors in plasma. Desialylation of LDL in turn endow them the capacity to accumulate in the smooth muscle cells of human aortic intima, highlighting the important role of desialylation in atherogenesis...
October 19, 2016: Current Pharmaceutical Design
Shizhong Ke, Shuzhen Chen, Zihui Dong, Christopher S Hong, Qi Zhang, Liang Tang, Pinghua Yang, Jian Zhai, Hexin Yan, Feng Shen, Zhengping Zhuang, Wen Wen, Hongyang Wang
: Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma (HCC). Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. Here we demonstrated an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas (TCGA). In the subset of HCC patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting impairment of respiratory metabolism, which sequentially led to depletion of α-ketoglutarate, stabilization of hypoxia inducible factor-α and expression of target genes such as EPO...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Li Zhou, Ping Chen, Yating Peng, Ruoyun Ouyang
Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction...
2016: Oxidative Medicine and Cellular Longevity
Ravi B Patel, Muthiah Vaduganathan, Sanjiv J Shah, Javed Butler
Atrial fibrillation (AF) and heart failure (HF) often coexist, and the outcomes of patients who have both AF and HF are considerably worse than those with either condition in isolation. Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical entity and accounts for approximately one-half of current HF. At least one-third of patients with HFpEF are burdened by comorbid AF. The current understanding of the relationship between AF and HFpEF is limited, but the clinical implications are potentially important...
October 20, 2016: Pharmacology & Therapeutics
Stefan M Ivanov, Roland G Huber, Jim Warwicker, Peter J Bond
Critical regulatory pathways are replete with instances of intra- and interfamily protein-protein interactions due to the pervasiveness of gene duplication throughout evolution. Discerning the specificity determinants within these systems has proven a challenging task. Here, we present an energetic analysis of the specificity determinants within the Bcl-2 family of proteins (key regulators of the intrinsic apoptotic pathway) via a total of ∼20 μs of simulation of 60 distinct protein-protein complexes. We demonstrate where affinity and specificity of protein-protein interactions arise across the family, and corroborate our conclusions with extensive experimental evidence...
October 17, 2016: Structure
Bo Zhang, Gui-Zhi Sun, Min-Ling Zhu, Yue Li, Dian-Jun Sun, Bo Zhang, Xiu-Ping Bai
OBJECTIVES: CST has been recently identified as a mediator of various beneficial effects in animal models of sepsis. At present, no data are available concerning the levels of CST in sepsis patients. In sepsis the plasma amino acid pattern is characterized by decreased branced chain amino acids (BCAAs). We investigated the levels of plasma CST or branched-chain α-ketoacid dehydrogenase kinase (BCKDK) and their relationship to component traits in patients with sepsis. DESIGN AND METHODS: We studied 228 patients and divided them into two groups based on severity of infection...
October 20, 2016: Peptides
Anke Maatz, Megan Wainwright, Andrew J Russell, Jane Macnaughton, Yan Yiannakou
BACKGROUND: The term 'difficult' is pervasively used in relation to medically unexplained symptoms (MUS) and patients with MUS. This article scrutinises the use of the term by analysing interview data from a study of secondary care specialists' experiences with and attitudes towards patients suffering from MUS. DESIGN: Qualitative design employing semi-structured open-ended interviews systematically analysed in three stages: first, data were analysed according to the principles of content analysis...
November 2016: Journal of Psychosomatic Research
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