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Dosage sensitivity

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https://www.readbyqxmd.com/read/28214913/assessment-of-efficacy-and-safety-of-the-herbal-medicinal-product-bno-1016-in-chronic-rhinosinusitis
#1
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
#2
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
#3
Jozef Al-Gousous, Yasuhiro Tsume, Maoqi Fu, Isam Salem, Peter Langguth
First introduced in the second half of the nineteenth 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 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28196600/genome-editing-in-hpscs-reveals-gata6-haploinsufficiency-and-a-genetic-interaction-with-gata4-in-human-pancreatic-development
#4
Zhong-Dong Shi, Kihyun Lee, Dapeng Yang, Sadaf Amin, Nipun Verma, Qing V Li, Zengrong Zhu, Chew-Li Soh, Ritu Kumar, Todd Evans, Shuibing Chen, Danwei Huangfu
Human disease phenotypes associated with haploinsufficient gene requirements are often not recapitulated well in animal models. Here, we have investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. We found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6...
February 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28192718/quantitative-determination-of-five-metabolites-of-aspirin-by-uhplc-ms-ms-coupled-with-enzymatic-reaction-and-its-application-to-evaluate-the-effects-of-aspirin-dosage-on-the-metabolic-profile
#5
Jian-Ping Li, Jian-Ming Guo, Er-Xin Shang, Zhen-Hua Zhu, Yang Liu, Bu-Chang Zhao, Jing Zhao, Zhi-Shu Tang, Jin-Ao Duan
Acetylsalicylic acid (Aspirin, ASA) is a famous drug for cardiovascular diseases in recent years. Effects of ASA dosage on the metabolic profile have not been fully understood. The purpose of our study is to establish a rapid and reliable method to quantify ASA metabolites in biological matrices, especially for glucuronide metabolites whose standards are not commercially available. Then we applied this method to evaluate the effects of ASA dosage on the metabolic and excretion profile of ASA metabolites in rat urine...
December 29, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28189123/impact-of-various-progestins-with-or-without-transdermal-testosterone-on-gonadotropin-levels-for-non-invasive-hormonal-male-contraception-a-randomized-clinical-trial
#6
M Zitzmann, J Rohayem, J Raidt, S Kliesch, N Kumar, R Sitruk-Ware, E Nieschlag
Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone(®) (NES), all in combination with transdermal testosterone (T)...
February 11, 2017: Andrology
https://www.readbyqxmd.com/read/28186847/cytogenetic-biomonitoring-in-individuals-exposed-to-cone-beam-ct%C3%AF-comparison-among-exfoliated-buccal-mucosa-cells%C3%AF-cells-of-tongue-and-epithelial-gingival-cells
#7
Pan Yang, Shuai Hao, Xu Gong, Gang Li
OBJECTIVES: To evaluate chromosomal damage and cytotoxicity in exfoliated buccal mucosa cells,cells of tongue and epithelial gingival cells from adults following cone beam CT scan, and to compare the sensitivity of the different exfoliated cells to a same dosage of ionizing radiation. METHODS: The study included 46 healthy participants (median age 27 years; age range 23-42 years) who had a cone beam CT scan. Exfoliated mucosa cells were collected immediately before the CBCT scan and 10 days after...
February 10, 2017: Dento Maxillo Facial Radiology
https://www.readbyqxmd.com/read/28182563/a-high-throughput-small-molecule-screen-identifies-synergism-between-dna-methylation-and-aurora-kinase-pathways-for-x-reactivation
#8
Derek Lessing, Thomas O Dial, Chunyao Wei, Bernhard Payer, Lieselot L G Carrette, Barry Kesner, Attila Szanto, Ajit Jadhav, David J Maloney, Anton Simeonov, Jimmy Theriault, Thomas Hasaka, Antonio Bedalov, Marisa S Bartolomei, Jeannie T Lee
X-chromosome inactivation is a mechanism of dosage compensation in which one of the two X chromosomes in female mammals is transcriptionally silenced. Once established, silencing of the inactive X (Xi) is robust and difficult to reverse pharmacologically. However, the Xi is a reservoir of >1,000 functional genes that could be potentially tapped to treat X-linked disease. To identify compounds that could reactivate the Xi, here we screened ∼367,000 small molecules in an automated high-content screen using an Xi-linked GFP reporter in mouse fibroblasts...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28177202/biofluid-triggered-burst-release-from-an-adaptive-covalently-assembled-dipeptide-nanocontainer-for-emergency-treatment
#9
Jinbo Fei, He Zhang, Anhe Wang, Chenchen Qin, Huimin Xue, Junbai Li
The construction of quickly dissociating containers holding bioactive components that meet the extreme requirements of emergency treatment is highly desirable but remains a great challenge. Here the use of small-molecule-induced dynamic covalent assembly is reported for simple and tunable fabrication of a biocompatible diphenylalanine-based nanocontainer toward rapidly responsive cargo delivery. The assembled nanocontainer can adaptively encapsulate various charged or neutral molecules. Upon biofluid trigger, the encapsulated molecules and bioactive proteins are released in a burst (within 5 s) from the nanocontainer due to highly sensitive deprotonation-mediated disruption of hydrogen bonding...
February 8, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28176905/effect-of-roll-compaction-on-granule-size-distribution-of-microcrystalline-cellulose-mannitol-mixtures-computational-intelligence-modeling-and-parametric-analysis
#10
Pezhman Kazemi, Mohammad Hassan Khalid, Ana Pérez Gago, Peter Kleinebudde, Renata Jachowicz, Jakub Szlęk, Aleksander Mendyk
Dry granulation using roll compaction is a typical unit operation for producing solid dosage forms in the pharmaceutical industry. Dry granulation is commonly used if the powder mixture is sensitive to heat and moisture and has poor flow properties. The output of roll compaction is compacted ribbons that exhibit different properties based on the adjusted process parameters. These ribbons are then milled into granules and finally compressed into tablets. The properties of the ribbons directly affect the granule size distribution (GSD) and the quality of final products; thus, it is imperative to study the effect of roll compaction process parameters on GSD...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28176757/dosage-sensitivity-is-a-major-determinant-of-human-copy-number-variant-pathogenicity
#11
Alan M Rice, Aoife McLysaght
Human copy number variants (CNVs) account for genome variation an order of magnitude larger than single-nucleotide polymorphisms. Although much of this variation has no phenotypic consequences, some variants have been associated with disease, in particular neurodevelopmental disorders. Pathogenic CNVs are typically very large and contain multiple genes, and understanding the cause of the pathogenicity remains a major challenge. Here we show that pathogenic CNVs are significantly enriched for genes involved in development and genes that have greater evolutionary copy number conservation across mammals, indicative of functional constraints...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28167244/impact-of-risperidone-on-leptin-and-insulin-in-children-and-adolescents-with-autistic-spectrum-disorders
#12
Pornpen Srisawasdi, Natchaya Vanwong, Yaowaluck Hongkaew, Apichaya Puangpetch, Somlak Vanavanan, Boontarika Intachak, Nattawat Ngamsamut, Penkhae Limsila, Chonlaphat Sukasem, Martin H Kroll
OBJECTIVE: To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs). DESIGN AND METHODS: In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein...
February 3, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28163961/the-adjuvant-use-of-calcium-fructoborate-and-borax-with-etanercept-in-patients-with-rheumatoid-arthritis-pilot-study
#13
Saad Abdulrahman Hussain, Sattar Jabir Abood, Faiq Isho Gorial
OBJECTIVE: This study was designed to evaluate the effects calcium fructoborate (CFB) and sodium tetraborate (NTB) as supplements in Iraqi patients with active rheumatoid arthritis (RA) maintained on etanercept. MATERIALS AND METHODS: A double-blind randomized placebo-controlled clinical trial with 60 days treatment period was carried out at Baghdad Teaching Hospital, Medical city, Baghdad, Iraq. Eighty RA patients were randomized into three groups to receive either 220 mg/day CFB, 55 mg/day NTB in capsule dosage form (equivalent to 6 mg elemental Boron), or placebo formula once daily...
January 2017: Journal of Intercultural Ethnopharmacology
https://www.readbyqxmd.com/read/28158150/electric-stimulation-for-pain-relief-in-patients-with-fibromyalgia-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#14
Ana Paula de Silva Salazar, Cinara Stein, Ritchele Redivo Marchese, Rodrigo Della Mea Plentz, Aline De Souza Pagnussat
BACKGROUND: Fibromyalgia (FM) is a syndrome whose primary symptoms include chronic widespread muscle pain and fatigue. The treatment of patients with FM aims to provide symptomatic relief and improvement in physical capacities to perform daily tasks and quality of life. Invasive or non-invasive electric stimulation (ES) is used for pain relief in patients with FM. OBJECTIVE: This systematic review aimed to assess the effects of treatment with ES, combined or not combined with other types of therapy, for pain relief in patients with FM...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28153763/multiply-repeatable-and-adjustable-on-demand-phototriggered-local-anesthesia
#15
Alina Y Rwei, Changyou Zhan, Bruce Wang, Daniel S Kohane
A phototriggerable system whereby patients could repeatedly and non-invasively control the timing and dosage of local anesthesia according to their needs would be beneficial for perioperative pain and perhaps obviate the need for oral narcotics. However, clinical application of phototriggerable systems have been limited by concerns over phototoxicity of lasers and limited tissue penetration of light. To address these limitations, we increased the devices' effective sensitivity to light by co-delivering a second compound, dexmedetomidine, that potentiates the effect of delivered local anesthetics...
January 31, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28149771/inhibition-of-proliferation-of-retinal-vascular-endothelial-cells-more-effectively-than-choroidal-vascular-endothelial-cell-proliferation-by-bevacizumab
#16
Bharani Krishna Mynampati, Kumar Sambhav, Sandeep Grover, Kakarla V Chalam
AIM: To evaluate the differential inhibitory effects of bevacizumab on cell proliferation of vascular endothelial growth factor (VEGF)-stimulated choroidal vascular endothelial cells (CVECs) and retinal vascular endothelial cells (RVECs) in vitro. METHODS: VEGF (400 ng/mL) enriched CVECs and RVECs were treated with escalating doses of bevacizumab (0.1, 0.5, 1, 1.5 and 2 mg/mL). Cell proliferation changes were analyzed with WST-1 assay and trypan blue exclusion assay at 48, 72h and 1wk...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28145783/the-budget-impact-of-using-enteric-coated-aspirin-325mg-immediate-release-omeprazole-40mg-to-prevent-recurrent-cardiovascular-events
#17
Wenjie Zhang, Yi Han, John G Fort, David Schofield, James P Tursi
OBJECTIVE: Aspirin (acetylsalicylic acid; ASA) is commonly used for secondary prevention of cardiovascular (CV) events but may be associated with gastrointestinal (GI) adverse events, which can reduce adherence. Use of ASA co-therapy with proton pump inhibitors in patients at risk may be suboptimal. PA32540 (Yosprala(TM)) is a coordinated-delivery tablet combining EC-ASA 325 mg and immediate-release omeprazole 40 mg. The objective of this flexible budget impact model was to project the financial consequences of introducing PA32540 325 mg/40 mg to prevent recurrent CV events while reducing ASA-associated GI events in US adults...
February 1, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28139463/microfluidic-chip-based-micro-rna-detection-through-the-combination-of-fluorescence-and-surface-enhanced-raman-scattering-techniques
#18
Zhile Wang, Shenfei Zong, Zhuyuan Wang, Lei Wu, Peng Chen, Binfeng Yun, Yiping Cui
We present a novel microfluidic chip based method for the detection of micro RNA (miRNA) via the combination of fluorescence and surface enhanced Raman scattering (SERS) spectroscopies. First, silver nanoparticles (Ag NPs) are immobilized onto a glass slide, forming a SERS enhancing substrate. Then a specificially designed molecular beacon (MB) is attached to the SERS substrate. The 3' end of the MB is decorated with a thiol group to facilitate the attachment of the MB, while the 5' end of the MB is labeled with an organic dye 6-FAM, which is used both as the fluorophore and SERS reporter...
March 10, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28135246/avian-w-and-mammalian-y-chromosomes-convergently-retained-dosage-sensitive-regulators
#19
Daniel W Bellott, Helen Skaletsky, Ting-Jan Cho, Laura Brown, Devin Locke, Nancy Chen, Svetlana Galkina, Tatyana Pyntikova, Natalia Koutseva, Tina Graves, Colin Kremitzki, Wesley C Warren, Andrew G Clark, Elena Gaginskaya, Richard K Wilson, David C Page
After birds diverged from mammals, different ancestral autosomes evolved into sex chromosomes in each lineage. In birds, females are ZW and males are ZZ, but in mammals females are XX and males are XY. We sequenced the chicken W chromosome, compared its gene content with our reconstruction of the ancestral autosomes, and followed the evolutionary trajectory of ancestral W-linked genes across birds. Avian W chromosomes evolved in parallel with mammalian Y chromosomes, preserving ancestral genes through selection to maintain the dosage of broadly expressed regulators of key cellular processes...
January 30, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28129818/-analysis-of-dalbavancin-in-animal-models
#20
Óscar Murillo, Cristina El-Haj
Multiresistant Gram-positive infections continue to pose a major clinical challenge and the development of new antibiotics is always desirable. Dalbavancin is a lipoglycopeptide with a prolonged half-life that allows long dosing intervals. In experimental models, its activity has been evaluated in distinct models and microorganisms, which limits the conclusions that can be drawn; however, the largest number of studies have been conducted in Staphylococcus aureus infection. Overall, dalbavancin has shown concentration-dependent efficacy and the parameters best explaining its activity are maximal pharmacodynamic concentration/minimal inhibitory concentration and the area under the curve/minimal inhibitory concentration...
January 2017: Enfermedades Infecciosas y Microbiología Clínica
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