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Jennifer L Cohen, Terrence B Crowley, Daniel E McGinn, Carey McDougall, Marta Unolt, Michele P Lambert, Beverly S Emanuel, Elaine H Zackai, Donna M McDonald-McGinn
22q11.2 deletion syndrome (DS) is the most frequent copy number variant (CNV) affecting ~1/1,000 fetuses and ~1/2,000-4,000 children, resulting in recognizable but variable findings across multiple organ systems. Patients with atypical features should prompt consideration of coexisting diagnoses due to additional genome-wide mutations, CNVs, or mutations/CNVs on the other allele, unmasking autosomal recessive conditions. Importantly, a dual diagnosis compounds symptoms and impacts management. We previously reported seven patients with 22q11...
September 23, 2018: American Journal of Medical Genetics. Part A
Ilina Datkhaeva, Valerie A Arboleda, T Niroshi Senaratne, Gelareh Nikpour, Cherise Meyerson, Yipeng Geng, Yalda Afshar, Emily Scibetta, Jeffrey Goldstein, Fabiola Quintero-Rivera, Barbara F Crandall, Wayne W Grody, Joshua Deignan, Carla Janzen
Nonimmune hydrops fetalis (NIHF) is a rare disorder with a high perinatal mortality of at least 50%. One cause of NIHF is generalized lymphatic dysplasia (GLD), a rare form of primary lymphedema of the extremities and systemic involvement including chylothoraces and pericardial effusions. An autosomal recessive form of GLD has been described, caused by variants in the PIEZO1 gene. It has been reported clinically to cause NIHF and childhood onset of facial and limb lymphedema, most of which were diagnosed postnatally...
September 23, 2018: American Journal of Medical Genetics. Part A
Govindaraj Saravanan, Theivendren Panneerselvam, Veerachamy Alagarsamy, Selvaraj Kunjiappan, Pavadai Parasuraman, Indhumathy Murugan, Pandurangan Dinesh Kumar
Hit, Lead & Candidate Discovery A series of 2-(2-substituted benzylidenehydrazinyl-2-oxopropyl)-3-(4-[4-oxo-2-phenylthiazolo din-3-yl]phenyl)quinazolin-4(3H)-one 7a-7l were synthesized and characterized by IR, 1 H-NMR, 13 C-NMR, mass spectroscopy and elemental analyses. In this present study, the density functionality theory was performed to identify drug stability. Further we introduced graph theoretical analysis by utilised Kyoto Encyclopedia of Genes and Genomes (KEGG) database and Cytoscape software to identify drug target...
September 23, 2018: Drug Development Research
Shuifeng Wang, Ye Zhao, Jinghua Guo, Yuan Liu
We have previously reported that Ricinus communis is a good candidate for the phytoremediation of Cd- and Zn-contaminated soil and for fuel production. In this study, changes in the activity of antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and guaiacol peroxidase, POD) and the contents of chlorophyll and malondialdehyde (MDA) in R. communis leaves under Cu, Zn, and Cd stress were examined. Compounds from the exudate of R. communis roots were collected and analyzed using GC-MS chromatograms...
September 22, 2018: Environmental Science and Pollution Research International
Abo El-Khair B El-Sayed, Wael M Aboulthana, Amal M El-Feky, Noha E Ibrahim, Mohamed M Seif
Paracetamol is the most commonly used analgesic-antipyretic drugs. Its excess use causes an acute hepatotoxicity. It is well known that the Bacillariophyta alga Amphora coffeaeformis is rich in many photosynthetic pigments with antioxidant activities as well as a series of biologically active substances. The current work has been designed to study the phytochemical composition of different A. coffeaeformis algal extracts to select the most effective one. It was verified that acetone A. coffeaeformis algal extract is rich in various pigments and polyphenolic compounds (β-carotene (9...
September 22, 2018: Molecular Biology Reports
B A Kume, J A Ayoade, J Oloche
Sixteen red Sokoto (RS) bucks having an average weight of 9.11 kg and aged 5-8 months were used to determine the performance and digestibility of diets containing graded levels of yam peel meal in a completely randomized design. Four diets were compounded to replace maize offal with yam peel meal (YPM) at 0% (T1), 50% (T2), 75% (T2), and 100% (T4) levels and fed to the red Sokoto bucks for 105 days. Results show that there was no effect of treatment on all the performance parameters measured. There was also no effect of treatment on dry matter, organic matter, crude protein, nitrogen free extract, and ether extract digestibility of RS bucks...
September 22, 2018: Tropical Animal Health and Production
Nicolás Vidal, Marcelo Loureiro, Andrea Cecilia Hued, Gabriela Eguren, Franco Teixeira de Mello
Aquatic organisms are exposed to a myriad of chemical compounds, with particular concerns focused on endocrine disruptors. Growing scientific evidence indicates that these compounds interfere with normal endocrine function and could affect the reproductive system of humans and wildlife. We analyzed the proportion of masculinized females, defined by elongation and fusion of the anal fin rays, and the extent of masculinization, masculinization index, defined by anal fin length divided by the standard length, of Cnesterodon decemmaculatus resident to areas of agricultural and urban-industrial activities in the Arroyo Colorado basin...
September 22, 2018: Ecotoxicology
Zhengguang Zhang, Jingjing Xu, Bing Liu, Feiyan Chen, Jiao Li, Yuchen Liu, Jiapeng Zhu, Cunsi Shen
Ponicidin (PON), a natural diterpenoid compound, has been shown to exhibit potent anticancer activities in a wide variety of cancers, including colorectal cancer (CRC). Nevertheless, the precise mechanisms underlying the anti-metastasis effect of PON have not yet been completely defined. The present study was designed to uncover the inhibitory effect of PON on epithelial-mesenchymal transition (EMT), migration and invasion of HCT116 cells induced by pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) in vitro, and liver metastasis in vivo...
September 22, 2018: Inflammopharmacology
V P Chhiba-Govindjee, K Mathiba, C W van der Westhuyzen, P Steenkamp, J K Rashamuse, S Stoychev, M L Bode, D Brady
Nitrilases are of commercial interest in the selective synthesis of carboxylic acids from nitriles. Nitrilase induction was achieved here in three bacterial strains through the incorporation of a previously unrecognised and inexpensive nitrilase inducer, dimethylformamide (DMF), during cultivation of two Rhodococcus rhodochrous strains (ATCC BAA-870 and PPPPB BD-1780), as well as a closely related organism (Pimelobacter simplex PPPPB BD-1781). Benzonitrile, a known nitrilase inducer, was ineffective in these strains...
September 22, 2018: Applied Microbiology and Biotechnology
Ibrahim Sulaiman, Khaishin Tan, Norhafizah Mohtarrudin, Jonathan Chee Woei Lim, Johnson Stanslas
Toluene diisocyanate (TDI) is a major cause of chemical-induced occupational asthma, which contributes about 15% of global asthma burden. Resistance and compounded side effects associated with the use of corticosteroid in asthma necessitate the search for alternative drugs. Andrographolide (AGP), a naturally occurring diterpene lactone is known to exhibit various bioactivities. Its ability to ameliorate cardinal features of allergic asthma was previously suggested in an eosinophilic asthma endotype. However, its potential antiasthma activity and mechanism of action in a neutrophilic occupational asthma model, as well as its effect on epithelial dysfunction remain unknown...
September 20, 2018: Pulmonary Pharmacology & Therapeutics
Joseph R Troisi
Odor cues and interoceptive cues can combine in promoting drug seeking behavior. Drug discrimination methodology was combined with odor-context conditioning in 8 male and 8 female rats. One drug (nicotine or EtOH) plus odorant (peppermint or anise) compound functioned as setting the occasion for sessions of food-reinforced nose poke responses (i.e., the SD ) that were maintained on a variable interval 30 sec schedule (VI-30), whereas the opposite drug (EtOH or nicotine) plus odorant (anise or peppermint) compound predicted intermixed sessions of non-reinforcement of nose poking (i...
September 20, 2018: Behavioural Processes
Rita Sigüeiro, Julian Loureiro, Patricia González-Berdullas, Antonio Mouriño, Miguel A Maestro
As part of our program on synthesis of labeled vitamin D metabolites and analogs, we describe here an efficient and versatile synthetic approach to 28,28,28-trideutero- 25-hydroxydihydrotachysterol2 where isotopic labeling was incorporated stereoselectively in the last step of the synthesis. This deuterated compound will allow the study this analog in vitro or in vivo and to measure AT10-like compounds in serum by LC-MS/MS.
September 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
Adrian Fabisiak, Pawel Brzeminski, Klaudia Berkowska, Ewa Marcinkowska, Rafal R Sicinski
The results presented in this paper constitute an extension of our synthetic efforts focused on 19-norvitamin D compounds possessing elongated 2-alkylidene substituents. Based on our previous results, molecular modeling studies, and docking experiments, we selected a novel 19-norcalcitriol analog with long chain at C-2 containing several ether moieties and terminated by 2-(pyridin-2'-yl)ethylamino fragment. It was expected that such structural modification might allow binding of transition metal by the ligand, increase solubility of the formed complexes as well as improve their affinity to the VDR...
September 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
Kirt R Phipps, Nigel Baldwin, Barry Lynch, Diane R Stannard, Alica Šoltesová, Ben Gilby, Marta H Mikš, Christoph H Röhrig
Lacto-N-tetraose (LNT) is one of the most abundant oligosaccharides that are endogenously present in human breast milk. To simulate the composition of human breast milk more closely, commercial infant formula can be supplemented with human-identical milk oligosaccharides, which are manufactured structurally identical versions of their naturally occurring counterparts. As part of the safety evaluation of LNT, in vitro genotoxicity tests and a subchronic oral gavage toxicity study (in neonatal Sprague-Dawley rats) were conducted...
September 19, 2018: Regulatory Toxicology and Pharmacology: RTP
Javad Akhtari, Roghiyeh Faridnia, Hamed Kalani, Reza Bastani, Amin Kazemi Beydokhti, Hossein Rezvan, Mahdi Fakhar
OBJECTIVES: The aim of this study was to evaluate the cytotoxicity and antileishmanial activities of carbon nanotube-bounded cisplatin (CP-CNTs) against both promastigotes and amastigotes of L. major in vitro. METHODS: Cisplatin bounded to single- (CP-SWCNTs) and multi-walled carbon nanotubes (CP-MWCNTs) were considered as test compounds. In addition, SWCNT, MWCNT, cisplatin, and Glucantime® were considered as controls. The effect of each compound was evaluated on both promastigote and amastigote stages and the results were compared with each other...
September 20, 2018: Journal of Global Antimicrobial Resistance
Zhong-Ping Jiang, Li-Wen Tian, Li Shen, Jun Wu
Nine new ent-abietanes, named decandrols A-I (1-9), which could be categorized into three groups (1, 2-6, 7-9), were isolated from the roots of an Indian mangrove, Ceriops decandra, collected in the swamp of Godavari estuary, Andhra Pradesh, together with six previously reported abietanes (10-15), of which the absolute configurations were first determined. The relative and absolute configurations of these compounds were unambiguously established by HR-ESIMS, extensive 1D and 2D NMR investigations, single-crystal X-ray diffraction analysis with Cu Kα radiation, and quantum-chemical electronic circular dichroism (ECD) calculations...
September 19, 2018: Fitoterapia
Lydia Woelflingseder, Giorgia Del Favero, Tina Blažević, Elke H Heiss, Maximilian Haider, Benedikt Warth, Gerhard Adam, Doris Marko
DON, NX-3 and butenolide (BUT) are secondary metabolites formed by Fusarium graminearum. Evidence for formation of DON-glutathione adducts exists in plants, and also in human liver (HepG2) cells mass spectrometric evidence for GSH-adduct formation was reported. NX-3 is a DON derivative lacking structural features for Thiol-Michael addition, while BUT has the structural requirements (conjugated double bond and keto group). In the present study, we addressed whether these structural differences affect levels of intracellular reactive oxygen species in HepG2 cells, and if intracellular GSH levels influence toxic effects induced by DON; NX-3 and BUT...
September 19, 2018: Toxicology Letters
Hao Helen Hou, Aniruddha Rajesh, Keyur Pandya, Joseph W Lubach, Ariel Muliadi, Edward Yost, Wei Jia, Karthik Nagapudi
Usage of the amorphous phase of compounds has become the method of choice to overcome oral bioavailability problems related to poor solubility. Due to the unstable nature of glasses, it is clear that the method preparation of the amorphous glass will have an impact on physical/chemical stability and in turn in vivo performance. The method of preparation can also have a profound impact on the mechanical properties of the amorphous phase. We have explored the impact of preparation method on the mechanical properties of an amorphous solid dispersion using a development compound, GDC-0810...
September 19, 2018: Journal of Pharmaceutical Sciences
F Ngono, J F Willart, G J Cuello, M Jimenez-Ruiz, F Affouard
In this paper, we show that crystalline lactulose can be amorphized directly in the solid state by mechanical milling. Moreover, compared to similar materials, the amorphization kinetics of lactulose is found to be very rapid and the amorphous state thus obtained appears to be very stable against recrystallization upon heating. These features make lactulose a model compound for this type of solid state transformation. The ease of crystalline lactulose to be amorphized upon milling is explained by comparing elastic constants of lactulose with those of several other disaccharides...
September 19, 2018: Journal of Pharmaceutical Sciences
Gerald B Kasting, Matthew A Miller, Terri D LaCount, Joanna Jaworska
A porous pathway feature has been added to an existing skin diffusion model (Dancik et al. 2013. Adv Drug Deliv Rev 65:221-236) in order to extend the range of applicability to highly polar solutes that do not readily diffuse across the stratum corneum lipid/corneocyte matrix. The porous pathway consists of two components: Pathway A is appendageal and is implemented as an array of aqueous shunts (the macropores) which themselves have microporous walls with transient aqueous pores (the micropores). Two varieties of shunts are discussed, one representing a terminal hair follicle, the other an eccrine sweat duct; however, the focus here is on the hair follicle...
September 19, 2018: Journal of Pharmaceutical Sciences
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