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Dosage sensitivity

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https://www.readbyqxmd.com/read/28334874/efficient-cnv-breakpoint-analysis-reveals-unexpected-structural-complexity-and-correlation-of-dosage-sensitive-genes-with-clinical-severity-in-genomic-disorders
#1
Ling Zhang, Jingmin Wang, Cheng Zhang, Dongxiao Li, Claudia M B Carvalho, Haoran Ji, Jianqiu Xiao, Ye Wu, Weichen Zhou, Hongyan Wang, Li Jin, Yang Luo, Xiru Wu, James R Lupski, Feng Zhang, Yuwu Jiang
Genomic disorders are the clinical conditions manifested by submicroscopic genomic rearrangements including copy number variants (CNVs). The CNVs can be identified by array-based comparative genomic hybridization (aCGH), the most commonly used technology for molecular diagnostics of genomic disorders. However, clinical aCGH only informs CNVs in the probe interrogated regions. Neither orientational information nor the resulting genomic rearrangement structure is provided, which is a key to uncovering mutational and pathogenic mechanisms underlying genomic disorders...
March 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28330530/spectrophotometric-methods-for-simultaneous-determination-of-sofosbuvir-and-ledipasvir-harvoni-tablet-comparative-study-with-two-generic-products
#2
Nisreen F Abo-Talib, Mohamed R El-Ghobashy, Marwa H Tammam
Sofosbuvir and ledipasvir are the first drugs in a combination pill to treat chronic hepatitis C virus. Simple, sensitive, and rapid spectrophotometric methods are presented for the determination of sofosbuvir and ledipasvir in their combined dosage form. These methods were based on direct measurement of ledipasvir at 333 nm (due to the lack of interference of sofosbuvir) over a concentration range of 4.0–14.0 μg/mL, with a mean recovery of 100.78 ± 0.64%. Sofosbuvir was determined, without prior separation, by third-derivative values at 281 nm; derivative ratio values at 265...
February 10, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28323493/microparticles-containing-erlotinib-loaded-solid-lipid-nanoparticles-for-treatment-of-non-small-cell-lung-cancer
#3
Zahra Bakhtiary, Jaleh Barar, Ayuob Aghanejad, Amir Ata Saei, Elhameh Nemati, Jafar Ezzati Nazhad Dolatabadi, Yadollah Omidi
Non-small cell lung cancer (NSCLC) patients with sensitizing mutations in the exons 18-21 of the epithelial growth factor receptor (EGFR) geneshowincreased kinase activity of EGFR. Hence, tyrosine kinase inhibitors (TKIs) such as erlotinib (ETB) havecommonly been used as the second line therapeutic option in metastatic NSCLC. While the ETB is available as an oral dosage form, the local delivery of this TKI to the diseased cells of the lung may ameliorate its therapeutic impacts. In the current study, we report on the development of ETB-loaded solid lipid nanoparticle (SLN) based formulation of dry powder inhaler (ETB-SLN DPI)...
March 21, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28317873/a-new-method-to-evaluate-the-dose-effect-relationship-of-a-tcm-formula-gegen-qinlian-decoction-focus-mode-of-integrated-biomarkers
#4
Zhi-Qiang Huang, Xue-Mei Fan, Yi-Ming Wang, Qiong-Lin Liang, Xiao-Lin Tong, Yu Bai, Ying-Meng Li, Guo-An Luo, Chao Chen
It is difficult to accurately evaluate the efficacy of traditional Chinese medicine (TCM), which leads to the uncertainty and complexity of dose-effect analysis. In this study we established the "Focus" mode of biomarkers to characterize the dose-effect relationship of Gegen Qinlian Decoction (GQD), a TCM formula for treating type 2 diabetes mellitus (2-DM). A rat model of 2-DM was established through high fat diet feeding combined with low-dose STZ injection. Rats with 2-DM were administered high, middle or low doses (6...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28314286/safety-and-tolerance-of-d-l-methadone-in-combination-with-chemotherapy-in-patients-with-glioma
#5
Julia Onken, Claudia Friesen, Peter Vajkoczy, Martin Misch
BACKGROUND/AIM: D,L-Methadone increases sensitivity toward chemotherapy of different tumor cell populations. We evaluated the safety and tolerance of additional use of D,L-methadone in patients with glioma in combination with chemotherapy. PATIENTS AND METHODS: The dosage, duration of therapy and side-effects related to D,L-methadone were recorded in 27 patients. Toxicity was assessed accordingly to the Common Toxicity Criteria (CTC) of the National Cancer Institute...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303653/utility-of-hantzsch-reaction-for-development-of-highly-sensitive-spectrofluorimetric-method-for-determination-of-alfuzosin-and-terazosin-in-bulk-dosage-forms-and-human-plasma
#6
Mohamed A Hammad, Mahmoud A Omar, Baher I Salman
A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm...
March 17, 2017: Luminescence: the Journal of Biological and Chemical Luminescence
https://www.readbyqxmd.com/read/28303329/diagnostic-performance-of-transient-elastography-for-detection-of-methotrexate-induced-liver-injury-using-roenigk-classification-in-asian-patients-with-psoriasis-a-retrospective-study
#7
Pasinee Rongngern, Leena Chularojanamontri, Chanisada Wongpraparut, Narumol Silpa-Archa, Watcharasak Chotiyaputta, Ananya Pongpaibul, Phunchai Charatcharoenwitthaya
Liver biopsy, the gold standard for monitoring methotrexate-induced liver fibrosis in psoriasis patients, has potential morbidity and mortality. Transient elastography (TE) has been widely used as an alternative non-invasive method. Currently, psoriasis-specific data of TE comparing to Roenigk histopathology is lacking. This retrospective study assessed the diagnostic performance of TE in the detection of methotrexate-induced liver injury and liver fibrosis in Asian psoriasis patients. Risk factors that associated with liver injury by TE and histopathology were also determined...
March 16, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28303322/super-sensitive-time-resolved-fluoroimmunoassay-for-thyroid-stimulating-hormone-utilizing-europium-iii-nanoparticle-labels-achieved-by-protein-corona-stabilization-short-binding-time-and-serum-preprocessing
#8
Tuomas Näreoja, Jessica M Rosenholm, Urpo Lamminmäki, Pekka E Hänninen
Thyrotropin or thyroid-stimulating hormone (TSH) is used as a marker for thyroid function. More precise and more sensitive immunoassays are needed to facilitate continuous monitoring of thyroid dysfunctions and to assess the efficacy of the selected therapy and dosage of medication. Moreover, most thyroid diseases are autoimmune diseases making TSH assays very prone to immunoassay interferences due to autoantibodies in the sample matrix. We have developed a super-sensitive TSH immunoassay utilizing nanoparticle labels with a detection limit of 60 nU L(-1) in preprocessed serum samples by reducing nonspecific binding...
March 16, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28296816/low-dose-radiation-3d-intraoperative-imaging-how-low-can-we-go-an-o-arm-%C3%A2-ct-scan-cadaveric-study
#9
Vishal Sarwahi, Monica Payares, Stephen Wendolowski, Beverly Thornhill, Yungtai Lo, Terry D Amaral
STUDY DESIGN: Cadaveric study OBJECTIVE.: The objective was to evaluate O-Arm®'s ability at low dose settings to assess intraoperative screw placement. SUMMARY OF BACKGROUND DATA: Accurate placement of pedicle screws is crucial because of proximity to vital structures. Malposition of screws may result in significant morbidity and potential mortality. O-arm® provides real-time, intra-op imaging of patient's anatomy and provides higher accuracy in scoliosis surgeries, avoiding risk to vital structures...
March 14, 2017: Spine
https://www.readbyqxmd.com/read/28296084/de-novo-loss-of-function-variants-in-stag2-are-associated-with-developmental-delay-microcephaly-and-congenital-anomalies
#10
Sureni V Mullegama, Steven D Klein, Milene V Mulatinho, Tharanga Niroshini Senaratne, Kathryn Singh, Dzung C Nguyen, Natalie M Gallant, Samuel P Strom, Shahnaz Ghahremani, Nagesh P Rao, Julian A Martinez-Agosto
The cohesin complex is an evolutionarily conserved multi-subunit protein complex which regulates sister chromatid cohesion during mitosis and meiosis. Additionally, the cohesin complex regulates DNA replication, DNA repair, and transcription. The core of the complex consists of four subunits: SMC1A, SMC3, RAD21, and STAG1/2. Loss-of-function mutations in many of these proteins have been implicated in human developmental disorders collectively termed "cohesinopathies." Through clinical exome sequencing (CES) of an 8-year-old girl with a clinical history of global developmental delay, microcephaly, microtia with hearing loss, language delay, ADHD, and dysmorphic features, we describe a heterozygous de novo variant (c...
March 11, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28288842/thermo-sensitive-isopentane-aerification-for-mucosal-lift-during-endoscopic-resection-in-animal-models-with-video
#11
Wenjie Liu, Min Wang, Lili Zhao, Min Wang, Xiang Wang, Zhining Fan, Li Liu
BACKGROUND AND AIMS: Mucosal lift is critical for successful endoscopic treatment. Normal saline solution (NS) is widely used as the submucosal filler, but its short persistency restricts clinical endoscopic submucosal dissection (ESD) procedure. In this study, thermo-sensitive isopentane was introduced for submucosal injection. With a 27.8°C boiling point, liquid isopentane could be easily applied, whereas gasification inflation could provide great support for submucosal lifting at body temperature...
March 10, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28287001/transplacental-passage-of-vancomycin
#12
Craig V Towers, Beth Weitz
OBJECTIVE: To evaluate a larger number of patients receiving a vancomycin dosing regimen of 20 mg/kg IV every 8 hours for Group B streptococcus (GBS) chemoprophylaxis and analyze maternal and neonatal cord blood levels at delivery. METHODS: We prospectively enrolled every mother that entered labor with a positive GBS culture and a high-risk penicillin allergy with resistance to clindamycin or unknown sensitivity. Maternal and cord blood vancomycin levels were obtained at delivery...
March 12, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28273668/large-duplications-can-be-benign-copy-number-variants-a-case-of-a-3-6-mb-xq21-33-duplication
#13
Marie-Laure Maurin, Chloé Arfeuille, Pascale Sonigo, Sophie Rondeau, Michel Vekemans, Catherine Turleau, Yves Ville, Valérie Malan
Segmental aneusomies are usually associated with clinical consequences, but an increasing number of nonpathogenic cytogenetically visible as well as large cryptic chromosomal imbalances have been reported. Here, we report a 3.6-Mb Xq21.33 microduplication detected prenatally on a female fetus which was inherited from a phenotypically normal mother and grandfather. It is assumed that male patients harboring Xq or Xp duplication present with syndromic intellectual disability because of functional disomy of the corresponding genes...
March 9, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28270043/roles-of-atp-sensitive-potassium-channel-in-modulating-gastric-tone-and-accommodation-in-dogs
#14
Shiying Li, Yong Lei, Jiande Dz Chen
OBJECTIVE: The ATP sensitive potassium (KATP) channel plays an important role in the regulation of resting membrane potential and membrane excitability. The role of the KATP channel in modulating gastric motility is unclear. The aim of this study was to investigate the role and mechanism of the KATP channel in modulating gastric tone and accommodation in dogs. MATERIALS AND METHODS: Gastric volume under a constant pressure reflecting gastric tone was measured using a barostat device in dogs equipped with a gastric cannula...
May 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28263849/chemical-profiles-and-pharmacological-activities-of-chang-kang-fang-a-multi-herb-chinese-medicinal-formula-for-treating-irritable-bowel-syndrome
#15
Qian Mao, Lei Shi, Zhi-Gang Wang, Yu-Hui Luo, Yin-Yu Wang, Xue Li, Min Lu, Jian-Min Ju, Jin-Di Xu, Ming Kong, Shan-Shan Zhou, Min-Qin Shen, Song-Lin Li
ETHNOPHARMACOLOGICAL RELEVANCE: Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown. AIM OF THE STUDY: To investigate the chemical profiles and effects of CKF on IBS model. MATERIALS AND METHODS: The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS)...
March 2, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28245378/-effects-of-pci-32765-and-dasatinib-on-the-acute-lymphoblastic-leukemic-cells-and-their-mechanisms
#16
Yuan Deng, Shan-Dong Tao, Xin Zhang, Jing-Jing Ma, Zheng-Mei He, Yue Chen, Zhi-Kui Deng, Liang Yu
OBJECTIVE: To investigate the effects of Btk inhibitor (PCI-32765) and BCR-ABL tyrosine kinase inhibitor (Dasatinib) on proliferation and apoptosis of acute lymphoblastic leukemia (ALL) cell lines (Sup-B15, RS4;11) and the possible mechanism. METHODS: RS4;11 and Sup-B15 cells were treated with PCI-32765 and Dasatinib, the cell proliferation and apoptosis were detected by CCK-8, the Btk and other apoptotic proteins were detected by Western blot. RESULTS: PCI-32765 could inhibit the proliferation of RS4;11 and Sup-B15 cells in a dose-dependent manner, Sup-B15 cells were more sensitive to PCI-32765 than RS4;11 cells, their IC50 were 3 µmol/L and 8 µmol/L respectively, the difference between them was statistically significant (P<0...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28243976/inhibition-of-cdk4-sensitizes-multidrug-resistant-ovarian-cancer-cells-to-paclitaxel-by-increasing-apoptosiss
#17
Yan Gao, Jacson Shen, Edwin Choy, Henry Mankin, Francis Hornicek, Zhenfeng Duan
PURPOSE: Overexpression of cyclin-dependent kinase (CDK) 4 has been observed in a variety of cancers and has been found to contribute to tumor cell growth and proliferation. However, the effect of inhibition of CDK4 in ovarian cancer is unknown. We investigated the therapeutic effect of the CDK4 inhibitor palbociclib in combination with paclitaxel in ovarian cancer cells. METHODS: Cell viabilities were determined by MTT assay after exposure to different dosages of palbociclib and/or paclitaxel...
February 27, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28214913/assessment-of-efficacy-and-safety-of-the-herbal-medicinal-product-bno-1016-in-chronic-rhinosinusitis
#18
J Palm, I Steiner, D Abramov-Sommariva, A Ammendola, S Mitzenheim, H Steindl, M Wonnemann, C Bachert
BACKGROUND: The objective of this clinical trial (CRS-02) was to assess the efficacy, safety and tolerability of two dosages of the herbal medicinal product BNO 1016 (Sinupret extract) in patients with chronic rhinosinusitis (CRS). METHODOLOGY: 929 patients suffering from CRS were enrolled in this randomised placebo-controlled trial with a treatment period of 12 weeks. The primary endpoint was the mean Major Symptom Score (MSS) in week 8 and week 12 compared to placebo...
February 19, 2017: Rhinology
https://www.readbyqxmd.com/read/28209329/prognostic-factors-of-hemorrhagic-complications-after-oxaliplatin-based-hyperthermic-intraperitoneal-chemotherapy-toward-routine-preoperative-dosage-of-von-willebrand-factor
#19
J-B Delhorme, L Sattler, F Severac, E Triki, I Gross, B Romain, S Rohr, L Grunebaum, C Brigand
BACKGROUND: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC-ox) induces specific morbidity with hemorrhagic complications (HC). The aim of this study was to identify preoperative, intraoperative and postoperative HC predictive factors after HIPEC-ox. METHODS: A prospective single center study that included all consecutive patients treated with curative-intent HIPEC-ox, whatever the origin of peritoneal disease, was conducted. All patients underwent systematic blood tests exploring primary hemostasis and endothelial activation before surgical incision (D0) and on postoperative days 2 (POD2) and 5 (POD5)...
February 2, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28199791/unpredictable-performance-of-ph-dependent-coatings-accentuates-the-need-for-improved-predictive-in-vitro-test-systems
#20
Jozef Al-Gousous, Yasuhiro Tsume, Maoqi Fu, Isam I Salem, Peter Langguth
First introduced in the second half of the 19th century, enteric coatings are commonly used to protect acid-labile drugs, reduce the risk of gastric side effects due to irritating drugs, or for local drug delivery to the lower gastrointestinal (GI) tract. The currently available enteric-coatings are based on pH-sensitive weakly acidic polymers. Despite the long history of their use, the causes behind their performance often being unpredictable have not been properly investigated with most of the attention being focused only on the gastric emptying...
February 28, 2017: Molecular Pharmaceutics
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