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https://www.readbyqxmd.com/read/28636208/a-phase-i-trial-of-prn1008-a-novel-reversible-covalent-inhibitor-of-bruton-s-tyrosine-kinase-in-healthy-volunteers
#1
Patrick F Smith, Janakan Krishnarajah, Philip A Nunn, Ron J Hill, Dane Karr, D Tam, Mohammad Masjedizadeh, Jens O Funk, Steve G Gourlay
AIM: To evaluate the safety, tolerability, and PK/PD of PRN1008, a novel BTK inhibitor, in healthy volunteers, and thus determine the dose range for future clinical studies. METHODS: This was a two-part randomized, placebo controlled study in healthy volunteers using a liquid formulation. Part I was a single ascending dose design with dose levels of 50 to 1200 mg (n=6 active, 2 placebo per cohort); Part II was a multiple ascending dose design, with dose regimens ranging from 300 mg to 900 mg daily, either qd or bd for 10 days...
June 21, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28636113/linking-re-i-and-pt-ii-chromophores-with-aminopyridines-a-simple-route-to-achieve-a-complicated-photophysical-behavior
#2
Igor O Koshevoy, Kristina S Kisel, Alexei S Melnikov, Elena V Grachova, Pipsa Hirva, Sergey P Tunik
The bifunctional aminopyridine ligands H2N-(CH2)n-4-C5H4N (n = 0, L1; 1, L2; 2, L3) have been utilized for the preparation of rhenium complexes [Re(phen)(CO)3(L1-L3)]+ (1-3). 2 and 3 with NH2-coordinated L2/L3 were coupled with cycloplatinated motifs {Pt(ppy)Cl} and {Pt(dpyb)}+ to give the bimetallic species [Re(phen)(CO)3(μ-L2/L3)Pt(ppy)Cl]+ (4, 6) and [Re(phen)(CO)3(μ-L2/L3)Pt(dpyb)]2+ (5, 7). In solution, complexes 4 and 6 show 3MLCT {Re}-based emission at 298 K, which changes the parentage to 3IL(ppy) state at 77 K...
June 21, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28635877/-a-neuropathic-component-of-lumboischialgia-mechanisms-of-development-and-treatment-approaches
#3
M V Churyukanov, G E Shevtsova, O I Zagorulko
Low back pain (LBP) is accompanied by the development of pain syndrome that spreads into the leg in 25-57% of patients. This is an important factor predicting the risk of transition of pain from acute to chronic and is an indirect indicator of disease severity. It is often impossible to specify the primary mechanism facilitated pain irradiation in lumboischialgia because many structures can cause analogous symptoms. Mechanisms of development of LBP are represented by nociceptive, neuropathic and psychogenic components...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28635612/consequences-of-lipopolysaccharide-and-n-3-polyunsaturated-fatty-acid-administration-on-aortic-function-of-spontaneously-hypertensive-rats
#4
Barbara Kaprinay, Ruzena Sotnikova, Karel Frimmel, Jakub Krizak, Iveta Bernatova, Jana Navarova, Ludmila Okruhlicova
The aim of the work was to study the delayed effect of lipopolysaccharide (LPS) administration on endothelial function of the aorta of rats with genetic hypertension. Further, the possibility to ameliorate LPS-induced changes by n-3 polyunsaturated fatty acids (n-3 PUFA) was tested. Rats received a bolus of 1 mg/kg LPS i.p.; n-3 PUFA were administered in the dose of 30 mg/kg daily for 10 days p.o.. Ten days after receiving of LPS, the body weight gain of rats was statistically lower compared to control rats (p < 0...
July 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/28635332/50-ethanol-extract-of-orthosiphon-stamineus-modulates-genotoxicity-and-clastogenicity-induced-by-mitomycin-c
#5
Dhamraa Waleed Al-Dualimi, Aman Shah Abdul Majid, Sarah Furqan Faisal Al-Shimary, Amal Aziz Al-Saadi, Raghdaa Al Zarzour, Muhammad Asif, Chern Ein Oon, Amin Malik Shah Abdul Majid
Herbal products contain a variety of compounds which may be useful in protecting against cellular damage caused by mutagens. Orthosiphon stamineus (O.s) also known as Cat whiskers. The herb has been shown anti-oxidative properties and can modulate key cellular proteins that have cytoprotective effect. The study aimed to evaluate the effects of different doses (250, 500 and 1000 mg kg(-1)) of 50% ethanol extract of O.s (Et. O.s) on micro-nucleated polychromatic erythrocytes (MNPCE), Polychromatic to normachromatic erythrocytes ratio (PCE/NCE), Mitotic index (MI), and Chromosomal aberration (CA) in Bab/c mice...
June 21, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28634647/erratum-to-training-guidelines-for-endovascular-stroke-intervention-an-international-multi-society-consensus-document
#6
S D Lavine, K Cockroft, B Hoh, N Bambakidis, A A Khalessi, H Woo, H Riina, A Siddiqui, J A Hirsch, W Chong, H Rice, J Wenderoth, P Mitchell, A Coulthard, T J Signh, C Phatouros, M Khangure, P Klurfan, K Ter Brugge, D Iancu, T Gunnarsson, O Jansen, M Muto, I Szikora, L Pierot, P Brouwer, J Gralla, S Renowden, T Andersson, J Fiehler, F Turjman, P White, A C Januel, L Spelle, Z Kulcsar, R Chapot, A Biondi, S Dima, C Taschner, M Szajner, A Krajina, N Sakai, Y Matsumaru, S Yoshimura, M Ezura, T Fujinaka, K Iihara, A Ishii, T Higashi, M Hirohata, A Hyodo, Y Ito, M Kawanishi, H Kiyosue, E Kobayashi, S Kobayashi, N Kuwayama, Y Matsumoto, S Miyachi, Y Murayama, I Nagata, I Nakahara, S Nemoto, Y Niimi, H Oishi, J Satomi, T Satow, K Sugiu, M Tanaka, T Terada, H Yamagami, O Diaz, P Lylyk, M V Jayaraman, A Patsalides, C D Gandhi, S K Lee, T Abruzzo, B Albani, S A Ansari, A S Arthur, B W Baxter, K R Bulsara, M Chen, J E Delgado Almandoz, J F Fraser, D V Heck, S W Hetts, M S Hussain, R P Klucznik, T M Leslie-Mawzi, W J Mack, R A McTaggart, P M Meyers, J Mocco, C J Prestigiacomo, G L Pride, P A Rasmussen, R M Starke, P J Sunenshine, R W Tarr, D F Frei, M Ribo, R G Nogueira, O O Zaidat, T Jovin, I Linfante, D Yavagal, D Liebeskind, R Novakovic, S Pongpech, G Rodesch, M Soderman, A Taylor, T Krings, D Orbach, L Picard, D C Suh, H Q Zhang
No abstract text is available yet for this article.
June 20, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28634199/characterising-cis-regulatory-variation-in-the-transcriptome-of-histologically-normal-and-tumour-derived-pancreatic-tissues
#7
Mingfeng Zhang, Soren Lykke-Andersen, Bin Zhu, Wenming Xiao, Jason W Hoskins, Xijun Zhang, Lauren M Rost, Irene Collins, Martijn van de Bunt, Jinping Jia, Hemang Parikh, Tongwu Zhang, Lei Song, Ashley Jermusyk, Charles C Chung, Bin Zhu, Weiyin Zhou, Gail L Matters, Robert C Kurtz, Meredith Yeager, Torben Heick Jensen, Kevin M Brown, Halit Ongen, William R Bamlet, Bradley A Murray, Mark I McCarthy, Stephen J Chanock, Nilanjan Chatterjee, Brian M Wolpin, Jill P Smith, Sara H Olson, Gloria M Petersen, Jianxin Shi, Laufey Amundadottir
OBJECTIVE: To elucidate the genetic architecture of gene expression in pancreatic tissues. DESIGN: We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. RESULTS: We identified 38 615 cis-eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis-eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0...
June 20, 2017: Gut
https://www.readbyqxmd.com/read/28634015/three-dimensional-3d-printed-model-for-deep-infiltrating-endometriosis-die-a-case-report
#8
Mobolaji O Ajao, Nisse V Clark, Tatiana Kelil, Sarah L Cohen, Jon I Einarsson
The combination of a thorough physical exam and imaging with either MRI or pelvic ultrasound are important in pre-operative planning for deep infiltrating endometriosis. Nevertheless, the 2-dimensional rendering of the pathology by imaging does not always accurately represent intra-operative findings. An in-depth topographical relationship and extent of surrounding tissue invasion can be better appreciated from 3-dimensional modeling. A 49 year old patient with history of endometriosis and persistent pain underwent pre-operative imaging with MRI that was consistent with infiltrating endometriosis...
June 17, 2017: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/28633926/synergic-stimulation-of-serotonin-5-ht1a-receptor-and-%C3%AE-2-adrenoceptors-for-neuropathic-pain-relief-preclinical-effects-of-2-substituted-imidazoline-derivatives
#9
Lorenzo Di Cesare Mannelli, Carla Ghelardini, Laura Micheli, Fabio Del Bello, Mario Giannella, Alessandro Piergentili, Wilma Quaglia
Neuropathic pain affects millions of people causing disability and impairing quality of life. Commonly used analgesics are generally characterized by limited therapeutic outcomes. The serotonin 5-HT1A receptor and the α2 adrenergic receptors are involved in central nociceptive mechanisms with a pivotal role in the inhibitory descending pain pathway. Since their stimulation may modulate the nervous signaling altered by neuropathies, the purpose of the present research is the study of the combined activation of 5-HT1A and α2 receptors by rationally designed imidazoline ligands ((S)-1 and 2-5) in a rat model of neuropathic pain (chronic constriction injury - CCI)...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28633825/structural-evolution-growth-mechanism-and-photoluminescence-properties-of-cuwo4-nanocrystals
#10
E L S Souza, J C Sczancoski, I C Nogueira, M A P Almeida, M O Orlandi, M S Li, R A S Luz, M G R Filho, E Longo, L S Cavalcante
Copper tungstate (CuWO4) crystals were synthesized by the sonochemistry (SC) method, and then, heat treated in a conventional furnace at different temperatures for 1h. The structural evolution, growth mechanism and photoluminescence (PL) properties of these crystals were thoroughly investigated. X-ray diffraction patterns, micro-Raman spectra and Fourier transformed infrared spectra indicated that crystals heat treated and 100°C and 200°C have water molecules in their lattice (copper tungstate dihydrate (CuWO4·2H2O) with monoclinic structure), when the crystals are calcinated at 300°C have the presence of two phase (CuWO4·2H2O and CuWO4), while the others heat treated at 400°C and 500°C have a single CuWO4 triclinic structure...
September 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28632254/osteogenic-potential-of-gingival-mesenchymal-stem-cells-over-titanium-machined-surfaces
#11
Julio A Carrion, Junaid Rajani, Mohamed Al Bahrawy, Xiaojun Chan, Tae Jin Kim, Srinivas Myneni, Vincent J Iacono
PURPOSE: To evaluate the biochemical composition of bone nodules deposited by gingival mesenchymal stem cells (GMSCs) over titanium machined surfaces in vitro. MATERIALS AND METHODS: GMSCs were isolated from healthy gingival tissues of patients undergoing crown-lengthening surgical procedures. GMSCs were characterized following the International Society for Cellular Therapy guidelines. After incubation of the GMSCs with titanium discs, osteogenic differentiation was induced for 28 days...
June 20, 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28632202/genome-wide-association-study-of-borderline-personality-disorder-reveals-genetic-overlap-with-bipolar-disorder-major-depression-and-schizophrenia
#12
S H Witt, F Streit, M Jungkunz, J Frank, S Awasthi, C S Reinbold, J Treutlein, F Degenhardt, A J Forstner, S Heilmann-Heimbach, L Dietl, C E Schwarze, D Schendel, J Strohmaier, A Abdellaoui, R Adolfsson, T M Air, H Akil, M Alda, N Alliey-Rodriguez, O A Andreassen, G Babadjanova, N J Bass, M Bauer, B T Baune, F Bellivier, S Bergen, A Bethell, J M Biernacka, D H R Blackwood, M P Boks, D I Boomsma, A D Børglum, M Borrmann-Hassenbach, P Brennan, M Budde, H N Buttenschøn, E M Byrne, P Cervantes, T-K Clarke, N Craddock, C Cruceanu, D Curtis, P M Czerski, U Dannlowski, T Davis, E J C de Geus, A Di Florio, S Djurovic, E Domenici, H J Edenberg, B Etain, S B Fischer, L Forty, C Fraser, M A Frye, J M Fullerton, K Gade, E S Gershon, I Giegling, S D Gordon, K Gordon-Smith, H J Grabe, E K Green, T A Greenwood, M Grigoroiu-Serbanescu, J Guzman-Parra, L S Hall, M Hamshere, J Hauser, M Hautzinger, U Heilbronner, S Herms, S Hitturlingappa, P Hoffmann, P Holmans, J-J Hottenga, S Jamain, I Jones, L A Jones, A Juréus, R S Kahn, J Kammerer-Ciernioch, G Kirov, S Kittel-Schneider, S Kloiber, S V Knott, M Kogevinas, M Landén, M Leber, M Leboyer, Q S Li, J Lissowska, S Lucae, N G Martin, F Mayoral-Cleries, S L McElroy, A M McIntosh, J D McKay, A McQuillin, S E Medland, C M Middeldorp, Y Milaneschi, P B Mitchell, G W Montgomery, G Morken, O Mors, T W Mühleisen, B Müller-Myhsok, R M Myers, C M Nievergelt, J I Nurnberger, M C O'Donovan, L M O Loohuis, R Ophoff, L Oruc, M J Owen, S A Paciga, B W J H Penninx, A Perry, A Pfennig, J B Potash, M Preisig, A Reif, F Rivas, G A Rouleau, P R Schofield, T G Schulze, M Schwarz, L Scott, G C B Sinnamon, E A Stahl, J Strauss, G Turecki, S Van der Auwera, H Vedder, J B Vincent, G Willemsen, C C Witt, N R Wray, H S Xi, A Tadic, N Dahmen, B H Schott, S Cichon, M M Nöthen, S Ripke, A Mobascher, D Rujescu, K Lieb, S Roepke, C Schmahl, M Bohus, M Rietschel
Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP...
June 20, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28632082/the-%C3%AE-helix-alignment-of-proteins-in-water-solution-toward-a-high-frequency-electromagnetic-field-a-ftir-spectroscopy-study
#13
Emanuele Calabrò, Salvatore Magazù
The aim of this article was to study the effects of mobile phone electromagnetic waves at 1750 MHz on the Amide I and Amide II vibration bands of some proteins in bidistilled water solution by means of Fourier transform infrared (FTIR) spectroscopy and Fourier self-deconvolution (FSD) analysis. The proteins that were used for the experiment were hemoglobin, myoglobin, bovine serum albumin and lysozyme. The exposure system consisted of microwaves emitted by an operational mobile phone at the frequency at 1750 MHz at the average power density of 1 W/m(2)...
June 20, 2017: Electromagnetic Biology and Medicine
https://www.readbyqxmd.com/read/28631914/-impact-of-cpap-therapy-on-erectile-function-during-sleep-and-testosterone-level-in-men-with-sleep-apnea-syndrome
#14
I M Madaeva, O N Berdina, N V Semenova, V V Madaev, I N Gutnik, L I Kolesnikova
The article presents the results of a polysomnographic study with simultaneous monitoring spontaneous nocturnal erections - Nocturnal Penile Tumescences (NPT) in 69 men with age-related androgen deficiency (AAD). Of these, 45 patients were diagnosed with obstructive sleep apnea syndrome (OSAS). In 34 of the 45 patients with OSAS, regimens of non-invasive ventilation with positive-positive airway pressure (CPAP) were selected. Titration was carried out using automatic CPAP-devices for 2 months. The control group (n=24) comprised men with AAD, matched by the "copy-pair" type without clinical manifestations of respiratory disturbances during sleep...
June 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28631912/-results-of-urethral-reconstruction-in-adults-after-multiple-hypospadias-repairs
#15
S I Gamidov, M G Shneiderman, D Yu Pushkar, A O Vasil'ev, A V Govorov, R I Ovchinnikov, A Yu Popova, R D Dusmukhamedov
AIM: To improve treatment results in patients after multiple hypospadias repairs by optimizing the postoperative management. MATERIALS AND METHODS: Eighty-two patients (mean age 48.1+/-15.3 years) with urethral strictures secondary to failed hypospadias repairs underwent staged graft urethroplasty using oral mucosa (cheek, lip, tongue) as a grafting material. In 62 patients, at the end of surgery the bladder was drained with a standard Foley catheter. In twenty patients the bladder was drained with a modified silicone urethral catheter, which had an additional channel for delivering drugs and removing the urethral wound effluent, and a second additional channel for inflating a balloon fixed to the catheter tube at different parts of the catheter...
June 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28631900/-experimental-development-and-rationale-for-a-renal-decellularization-protocol-with-subsequent-comprehensive-assessment-of-the-biological-scaffold
#16
P V Glybochko, S N Alekseenko, E A Gubareva, E V Kuevda, A A Basov, A S Sotnichenko, S S Dzhimak, I S Gumenyuk, I Kh Egiev, V N Chechelyan, R Z Nakokhov, O M Lyasota, Yu V Teterin
Chronic renal failure (CRF) is one of the most challenging problems of contemporary medicine. Patients with chronic renal failure usually need renal replacement therapy as either hemodialysis, peritoneal dialysis or a kidney transplant. The latter is the most promising option for end-stage kidney disease. However, the shortage of donor organs, the complexity of their delivery, the difficulty in finding an immunologically compatible donor and the need for lifelong immunosuppression triggered advances in modern tissue engineering...
June 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28631810/flavonoids-of-lotus-nelumbo-nucifera-seed-embryos-and-their-antioxidant-potential
#17
Mingzhi Zhu, Ting Liu, Chunyun Zhang, Mingquan Guo
Flavonoids from lotus (Nelumbo nucifera) seed embryos were fractionated over a macroporous resin chromatography into 2 main fractions (I and II), and subsequently identified by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS(2) ). Sixteen flavonoids were identified in lotus seed embryos, including 8 flavonoid C-glycosides and 8 flavonoid O-glycosides, in which the flavonoid C-glycosides were the main flavonoids. Among them, 2 flavonoid O-glycosides (luteolin 7-O-neohesperidoside and kaempferol 7-O-glucoside) were identified in lotus seed embryos for the 1st time...
June 20, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28631791/room-temperature-sintering-of-polar-zno-nanosheets-ii-mechanism
#18
Amparo Fernández-Pérez, Verónica Rodríguez-Casado, Teresa Valdés-Solís, Gregorio Marbán
In a previous work by the authors (A. Fernández-Pérez el al., Room temperature sintering of polar ZnO nanosheets: I-evidence, 2017, DOI: 10.1039/C7CP02306E), polar ZnO nanosheets were stored at room temperature under different atmospheres and the evolution of their textural and crystal properties during storage was followed. It was found that the specific surface area of the nanosheets drastically decreased during storage, with a loss of up to 75%. The ZnO crystals increased in size mainly through the partial merging of their polar surfaces at the expense of narrow mesoporosity, in a process triggered by the action of moisture, oxygen and, in their absence, by light...
June 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28631776/-panoramica-sui-risultati-degli-studi-pre-clinici-sugli-effetti-dell-epigallocatechina-gallato-la-pi%C3%A3-abbondante-catechina-presente-nel-t%C3%A3-verde-nel-trattamento-del-cancro-al-pancreas
#19
Sabrina Bimonte, Marco Cascella, Maddalena Leongito, Raffaele Palaia, Domenico Caliendo, Francesco Izzo, Arturo Cuomo
Riassunto. Il tumore del pancreas è una delle principali cause di mortalità e morbilità in tutto il mondo. Nonostante la resezione chirurgica rimanga il trattamento elettivo per questa malattia, solo una minoranza dei pazienti è candidata a intervento chirurgico, in quanto la diagnosi è molto spesso tardiva. Recentemente, nuovi schemi di chemioterapia con la combinazione di diversi farmaci, come il FOLFIRINOX (5-FU, leucovorina, irinotecan, and oxaliplatino), hanno mostrato di migliorare la sopravvivenza libera da progressione di malattia...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28631774/-il-ruolo-di-niraparib-nel-trattamento-del-carcinoma-ovarico-attualit%C3%A3-e-prospettive
#20
Ilaria Sabatucci, Domenica Lorusso
Riassunto. I PARP inibitori interferiscono con la riparazione del danno nella singola elica del DNA determinando una progressione del difetto nella doppia elica. In circa il 50% delle pazienti con carcinoma dell'ovaio sieroso di alto grado sono presenti difetti nei meccanismi di ricombinazione omologa, deputati alla riparazione del danno della doppia elica del DNA. L'incapacità di riparare il danno si traduce nella morte cellulare, un processo definito "letalità sintetica". Nella famiglia dei PARP inibitori il niraparib è stato il primo a essere approvato dalla FDA nel trattamento delle pazienti con carcinoma ovarico ricorrente indipendentemente dalla presenza o assenza di mutazioni BRCA...
June 2017: Recenti Progressi in Medicina
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