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https://www.readbyqxmd.com/read/28727763/loss-of-receptor-activity-modifying-protein-2-in-mice-causes-placental-dysfunction-and-alters-pth1r-regulation
#1
Mahita Kadmiel, Brooke C Matson, Scott T Espenschied, Patricia M Lenhart, Kathleen M Caron
Receptor activity-modifying protein 2 (Ramp2) is a single-pass transmembrane protein that heterodimerizes with several family B G-protein coupled receptors to alter their function. Ramp2 has been primarily characterized in association with calcitonin receptor-like receptor (Calcrl, CLR), forming the canonical receptor complex for the endocrine peptide adrenomedullin (Adm, AM). However, we previously demonstrated that Ramp2+/- female mice display a constellation of endocrine-related phenotypes that are distinct from those of Adm+/- and Calcrl+/- mice, implying that RAMP2 has physiological functions beyond its canonical complex...
2017: PloS One
https://www.readbyqxmd.com/read/28727650/acquired-external-auditory-canal-atresia-a-comparison-of-acellular-dermal-matrix-and-split-thickness-skin-grafting-techniques
#2
Michel A Evans, Eric M Sugihara, Eleanor Y Chan
OBJECTIVE: To describe the use of acellular dermal matrix (ADM) in the repair of acquired external auditory canal atresia (AEACA), and compare surgical results to AEACA repair by split-thickness skin grafting (STSG). STUDY DESIGN: Retrospective chart review. SETTING: Neurotology clinical practice. PATIENTS AND INTERVENTION: From 2007 to 2015, 25 AEACA surgeries (8 ADM and 17 STSG) were identified meeting inclusion and exclusion criteria...
July 19, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28725874/metabolites-of-alectinib-in-human-their-identification-and-pharmacological-activity
#3
Mika Sato-Nakai, Kosuke Kawashima, Toshito Nakagawa, Yukako Tachibana, Miyuki Yoshida, Kenji Takanashi, Peter N Morcos, Martin Binder, David J Moore, Li Yu
Two metabolites (M4 and M1b) in plasma and four metabolites (M4, M6, M1a and M1b) in faeces were detected through the human ADME study following a single oral administration of [(14)C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28725506/an-aberrant-abductor-digiti-minimi-muscle-crossing-guyon-s-canal
#4
YongSeok Nam, SeungHwan Hwang, SuRak Eo
Anomalous hypothenar muscles in the wrist are relatively common with 47% prevalence, and their possible consequences associated with Guyon's canal are well known. The accessory of the abductor digiti minimi muscle (ADM) is known to be one of the causes of ulnar tunnel syndrome or ulnar artery thrombosis. A unique ADM was found in the volar wrist region of an 87-year-old male cadaver passing through Guyon's canal.
August 2017: Journal of Wrist Surgery
https://www.readbyqxmd.com/read/28720525/motor-resonance-during-action-observation-is-gaze-contingent-a-tms-study
#5
Giorgia D'Innocenzo, Claudia C Gonzalez, Alexander V Nowicky, A Mark Williams, Daniel T Bishop
When we observe others performing an action, visual input to our mirror neuron system is reflected in the facilitation of primary motor cortex (M1), a phenomenon known as 'motor resonance'. However, it is unclear whether this motor resonance is contingent upon our point-of-gaze. In order to address this issue, we collected gaze data from participants as they viewed an intransitive action - thumb abduction/adduction - under four conditions: with natural gaze behaviour (free viewing) and with their gaze fixated on each of three predetermined loci at various distances from the prime mover...
July 15, 2017: Neuropsychologia
https://www.readbyqxmd.com/read/28708399/development-and-validation-of-a-computational-model-ensemble-for-the-early-detection-of-bcrp-abcg2-substrates-during-the-drug-design-stage
#6
Melisa Edith Gantner, Roxana Noemí Peroni, Juan Francisco Morales, María Luisa Villalba, María Esperanza Ruiz, Alan Talevi
Breast Cancer Resistance Protein (BCRP) is an ATP-dependent efflux transporter linked to the multidrug resistance phenomenon in many diseases such as epilepsy and cancer, and a potential source of drug interactions. For those reasons, the early identification of substrates and non-substrates of this transporter during the drug discovery stage is of great interest. We have developed a computational non-linear model ensemble based on conformational independent molecular descriptors using a combined strategy of genetic algorithms, J48 decision tree classifiers and data fusion...
July 14, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28705694/rotator-cuff-bridging-repair-using-acellular-dermal-matrix-in-large-to-massive-rotator-cuff-tears-histologic-and-clinical-analysis
#7
Jong Ok Kim, Jong-Ho Lee, Kwang-Sup Kim, Jong-Hun Ji, Sung-Jun Koh, Jae-Ho Lee
BACKGROUND: This study investigated the efficacy of the bridging repair using an acellular dermal matrix (ADM) and an ADM with stem cells in rabbits. Also investigated were clinical outcomes of ADM bridging repair for large to massive rotator cuff tears. MATERIALS AND METHODS: ADM, with and without stem cells, was used to cover a 5- × 5-mm-sized cuff defect in 17 rabbits, and biomechanical, histologic, and immunohistochemical analyses were conducted. Also evaluated were 24 patients with large to massive rotator cuff tears after ADM bridging repair...
July 10, 2017: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/28699507/quinolones-and-fluroquinolones-metabolism-and-resistance-in-salmonella-typhimurium-a-mini-review
#8
B Preethi, V Shanthi, K Ramanathan
Salmonella enterica serovars causes substantial morbidity and mortality worldwide. More than 2500 different serotypes of Salmonella were identified to date. In particular, Salmonella enterica serovar typhimurium is the most important serotype of Salmonella transmitted from animals to humans in most parts of the world. They are associated with an estimated 1 million deaths annually. Quinolones are an important class of broad-spectrum antimicrobials has been utilized in the treatment option for over 40 years...
July 10, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28698450/analytical-techniques-and-pharmacokinetics-of-gastrodia-elata-blume-and-its-constituents
#9
REVIEW
Jinyi Wu, Bingchu Wu, Chunlan Tang, Jinshun Zhao
Gastrodia elata Blume (G. elata), commonly called Tianma in Chinese, is an important and notable traditional Chinese medicine (TCM), which has been used in China as an anticonvulsant, analgesic, sedative, anti-asthma, anti-immune drug since ancient times. The aim of this review is to provide an overview of the abundant efforts of scientists in developing analytical techniques and performing pharmacokinetic studies of G. elata and its constituents, including sample pretreatment methods, analytical techniques, absorption, distribution, metabolism, excretion (ADME) and influence factors to its pharmacokinetics...
July 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28697727/intermedin-attenuates-renal-fibrosis-by-induction-of-heme-oxygenase-1-in-rats-with-unilateral-ureteral-obstruction
#10
Xi Qiao, Lihua Wang, Yanhong Wang, Xiaole Su, Yufeng Qiao, Yun Fan, Zhiqiang Peng
BACKGROUND: Intermedin [IMD, adrenomedullin-2 (ADM-2)] attenuates renal fibrosis by inhibition of oxidative stress. However, the precise mechanisms remain unknown. Heme oxygenase-1 (HO-1), an antioxidant agent, is associated with antifibrogenic effects. ADM is known to induce HO-1. Whether IMD has any effect on HO-1 is unclear. Herein, we determined whether the antifibrotic properties of IMD are mediated by induction of HO-1. METHODS: Renal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on male Wistar rats...
July 11, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28694764/2-pyrazoline-derivatives-in-neuropharmacology-synthesis-adme-prediction-molecular-docking-and-in-vivo-biological-evaluation
#11
Savita Upadhyay, Avinash C Tripathi, Sarvesh Paliwal, Shailendra K Saraf
A novel series of 1,3,5-trisubstituted-2-pyrazoline derivatives (PFC-1 to PFC-16) were synthesized in a three step reaction using conventional and microwave assisted green chemistry approach. The synthesized derivatives were characterized and their chemical structures were established by various physicochemical methods such as IR, Mass, (1)H-NMR, (13)C-NMR and elemental analysis. The synthesized compounds were tested for their neuropharmacological potential. The compounds exhibited significant antidepressant and anti-anxiety activities against various behavioral in vivo models...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28693910/antileishmanial-potential-of-fused-5-pyrazin-2-yl-4h-1-2-4-triazole-3-thiols-synthesis-biological-evaluations-and-computational-studies
#12
Sanjeev R Patil, Ashish Asrondkar, Vrushali Patil, Jaiprakash N Sangshetti, Firoz A Kalam Khan, Manoj G Damale, Rajendra H Patil, Anil S Bobade, Devanand B Shinde
A series of newer 1,2,4-triazole-3-thiol derivatives 5(a-m) and 6(a-i) containing a triazole fused with pyrazine moiety of pharmacological significance have been synthesized. All the synthesized compounds were screened for their in vitro antileishmanial and antioxidant activities. Compounds 5f (IC50=79.0µM) and 6f (IC50=79.0µM) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50=490.0µM). Compounds 5b (IC50=13.96µM) and 6b (IC50=13.96µM) showed significant antioxidant activity...
June 22, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28693180/soluble-urokinase-type-plasminogen-activator-receptor-and-urokinase-type-plasminogen-activator-receptor-contribute-to-chemoresistance-in-leukemia
#13
Hong Guo, Lan-Xia Zhou, Haizhen Ma, Bei Liu, Juan Cheng, Yun-Yun Ma, Li Zhao
The soluble urokinase-type plasminogen activator receptor (suPAR) and the urokinase-type plasminogen activator receptor (uPAR) have been proposed as useful biomarkers of tumor progression. Recently, suPAR was associated with chemoresistance in lung cancer. However, its clinical significance in leukemia has not previously been investigated. The present study examined the plasma levels of suPAR and the expression of the uPAR on bone marrow (BM) cells in 86 patients with leukemia at diagnosis prior to chemotherapy and 26 normal subjects (control group)...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691304/pharmacophore-feature-prediction-and-molecular-docking-approach-to-identify-novel-anti-hcv-protease-inhibitors
#14
Arthi V, Rambabu M, Jayanthi S, Febin Prabhu Dass J
Discovering a potential drug for HCV treatment is a challenging task in the field of drug research. This study initiates with computational screening and modeling of promising ligand molecules. The foremost modeling method involves the identification of novel compound and its molecular interaction based on pharmacophore features. A total of 197 HCV compounds for NS3/4A protein target were screened for our study. The pharmacophore models were generated using PHASE module implemented in Schrodinger suite. The pharmacophore features include one hydrogen bond acceptor, one hydrogen bond donor and three hydrophobic sites...
July 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28690172/managing-colonic-inflammation-associated-gut-derangements-by-systematically-optimised-and-targeted-ginger-extract-lactobacillus-acidophilus-loaded-pharmacobiotic-alginate-beads
#15
Parneet Kaur Deol, Pragyanshu Khare, Dhirendra Pratap Singh, Girish Soman, Mahendra Bishnoi, Kanthi Kiran Kondepudi, Indu Pal Kaur
Presently, we explore a cobiotic- ginger extract (GE; antioxidant-antiinflammatory) and Lactobacillus acidophilus (LAB, probiotic), for control of oxidative-stress, inflammation and dysbiosis mediated gut ailments. Since orally administered LAB looses viability while GE is a gastric irritant with poor ADME, we encapsulated them into calcium-alginate beads. Water-loving, viscolysing, and osmotic-building effects of polyethylene glycol were used to address poor probiotic encapsulation (≤10%) by effective sealing of numerous fine voids formed in the alginate gel...
July 6, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28689398/an-electrode-configuration-for-recording-muscle-motor-evoked-potentials-in-the-upper-extremities-during-intraoperative-neurophysiological-monitoring
#16
Young-Doo Choi, Seung-Hyun Jin, Chi-Heon Kim, Gil Ho Kwak, Bo Eun Kim, Chun Kee Chung
OBJECTIVE: The main aim of the present study is to examine the electrode configurations used to record the muscle motor evoked potential (mMEP) in the upper extremities during surgery with the goal of producing a high and stable mMEP signal, in particular among the abductor pollicis brevis (APB), abductor digiti minimi (ADM), and across the APB-ADM muscles, which have been widely used for the mMEP in the upper extremities. METHODS: Thirty right-handed patients were recruited in this prospective study...
July 2017: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/28684727/plasmid-plxsn-mediated-adrenomedullin-gene-therapy-for-cerebral-vasospasm-following-subarachnoid-hemorrhage-in-rats
#17
Xin Li, Xiaoshuang Xia, Xin Li
BACKGROUND The aim of this study was to investigate the protective effect of ADM gene mediated by plasmid pVAX1 on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). MATERIAL AND METHODS The recombinant plasmid pVAX-ADM was successfully established, and 40 SD rats were randomly divided into normal saline, pVAX1, pVAX1-ADM low-dose, pVAX1-ADM mid-dose, and pVAX1-ADM high-dose groups. The circumference and diameter of basilar artery, diameter of middle cerebral artery and internal carotid artery, and thickness of basilar artery wall were observed...
July 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28678597/disposition-profiling-and-identification-of-emixustat-and-its-metabolites-in-humans
#18
Michael E Fitzsimmons, Gang Sun, Vladimir Kuksa, Michael J Reid
Emixustat is a small molecule that potently inhibits retinal pigment epithelium 65 isomerohydrolase. Emixustat is in clinical development for the treatment of various retinopathies (i.e. Stargardt disease and diabetic retinopathy). A human absorption, distribution, metabolism, and excretion (ADME) study was conducted with a single dose of [(14)C]-emixustat in healthy male subjects. Total (14)C content in plasma, urine, and faeces was determined using accelerator mass spectrometry (AMS), and metabolic profiles in pooled plasma and urine were investigated by both HPLC-AMS and 2D LC-MS/MS...
July 5, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28677724/tnfr2-promotes-adriamycin-resistance-in-breast-cancer-cells-by-repairing-dna-damage
#19
Fuqian Yang, Nana Zhao, Nan Wu
In recent years, tumor necrosis factor receptor 2 (TNFR2) has attracted increasing attention for its important roles in promoting proliferation, migration and angiogenesis in several types of cancer. However, its role in drug resistance remain unclear. In the present study, TNFR2 expression levels in MDA‑MB‑231 and MCF‑7 breast cancer cells were demonstrated to be associated with Adriamycin (ADM) resistance. Silencing of TNFR2 in MCF‑7 cells significantly inhibited ADM resistance, while overexpression of TNFR2 in MDA‑MB‑231 cells significantly enhanced ADM resistance...
June 30, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28669907/centre-surround-organization-of-fast-sensorimotor-integration-in-human-motor-hand-area
#20
Raffaele Dubbioso, Estelle Raffin, Anke Karabanov, Axel Thielscher, Hartwig Roman Siebner
Using the short-latency afferent inhibition (SAI) paradigm, transcranial magnetic stimulation (TMS) of the primary motor hand area (M1HAND) can probe how sensory input from limbs modulates corticomotor output in humans. Here we applied a novel TMS mapping approach to chart the spatial representation of SAI in human hand-knob. We hypothesized SAI is somatotopically expressed in M1HAND depending on both the site of peripheral electrical nerve stimulation and the cortical spot targeted by TMS within M1HAND. The left index or little finger was stimulated 23 ms before focal single-pulse TMS of the right M1HAND...
June 29, 2017: NeuroImage
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