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https://www.readbyqxmd.com/read/29346445/transcriptome-analysis-of-skin-fibroblasts-with-dominant-negative-col3a1-mutations-provides-molecular-insights-into-the-etiopathology-of-vascular-ehlers-danlos-syndrome
#1
Nicola Chiarelli, Giulia Carini, Nicoletta Zoppi, Marco Ritelli, Marina Colombi
Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures...
2018: PloS One
https://www.readbyqxmd.com/read/29345446/the-first-south-american-case-of-pre-implantation-genetic-diagnosis-to-select-compatible-embryo-for-cord-blood-transplantation-as-treatment-for-sickle-cell-anemia
#2
Ciro D Martinhago, Kalina Rn Endo, Mariana A Oliveira, Alex Mm Dias, Gislaine S Pereira, Augusto M Azzolini, Paula Rq Estrada, Caio G Bruzaca, Ana Carolina N Martinhago
Sickle cell anemia is an inherited systemic hemoglobinopathy that affects hemoglobin production in red blood cells, leading to early morbidity and mortality. It is caused by a homozygous nucleotide substitution (c.20A>T) in the β-globin gene (HBB) that changes a glutamic acid to a valine in the protein. We present a case report of a fertile couple, both carriers of the sickle cell anemia mutation, with one affected daughter. Six cycles of assisted reproductive techniques were performed, resulting in 53 embryos in cleavage stage...
January 18, 2018: JBRA Assisted Reproduction
https://www.readbyqxmd.com/read/29345044/preclinical-characterisation-of-absorption-distribution-metabolism-and-excretion-properties-of-tak-063
#3
Kimio Tohyama, Miyako Sudo, Akio Morohashi, Suguru Kato, Junzo Takahashi, Yoshihiko Tagawa
TAK-063 is currently being developed to treat schizophrenia. In this study, we investigated the absorption, distribution, metabolism and excretion (ADME) properties of TAK-063 using several paradigms. Following oral administration of TAK-063 at 0.3 mg/kg, bioavailability of TAK-063 was 27.4% in rats and 49.5% in dogs with elimination half-lives of 3.1 hr in rats and 3.7 hr in dogs. TAK-063 is a highly permeable compound without P-glycoprotein (P-gp) or breast cancer resistance protein substrate liability and can be readily absorbed into systemic circulation via the intestine...
January 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29336266/design-synthesis-evaluation-and-computational-studies-of-nipecotic-acid-acetonaphthone-hybrids-as-potential-antiepileptic-agents
#4
Ankit Seth, Piyoosh A Sharma, Avanish Tripathi, Priyanka K Choubey, Pavan Srivastava, Prabhash N Tripathi, Sushant Kumar Shrivastava
BACKGROUND: Nipecotic acid is considered to be one of the most potent inhibitors of neuronal and glial γ- aminobutyric acid (GABA) uptake in vitro. However nipecotic acid does not readily cross the blood-brain barrier (BBB) following peripheral administration, owing to its hydrophilic nature. OBJECTIVE: A series of substituted acetonaphthones tethered nipecotic acid derivatives were designed and synthesized with an aim to improve the lipophilicity and the blood-brain barrier (BBB) permeation...
January 15, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29334207/screening-for-causative-mutations-of-major-prolificacy-genes-in-iranian-fat-tailed-sheep
#5
Ramin Abdoli, Seyed Ziaeddin Mirhoseini, Navid Ghavi Hossein-Zadeh, Pouya Zamani
Background: The presence of different missense mutations in sheep breeds have shown that the bone morphogenetic protein receptor 1B (BMPR1B), bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes play a vital role in ovulation rate and prolificacy in ewes. Therefore, the present study aims to investigate BMPR1B, BMP15 and GDF9 gene mutations in prolific ewes of Iranian fat-tailed Lori-Bakhtiari sheep. MATERIALS AND METHODS: In the present experimental study, genomic DNA was extracted from whole blood of 10 prolific Lori-Bakhtiari ewes with at least two twinning records in the first four parities to identify point mutations of the BMPR1B, BMP15 and GDF9 genes, using DNA sequencing...
April 2018: International Journal of Fertility & Sterility
https://www.readbyqxmd.com/read/29333722/cardiovascular-adjustments-during-anticipated-postural-changes
#6
Neesirg M Patel, Ethan A G Baker, Samuel R Wittman, Isaiah C Engstrom, George H Bourdages, Andrew A McCall, Derek M Miller, Bill J Yates
It is well-documented that feedforward cardiovascular responses occur at the onset of exercise, but it is unclear if such responses are associated with other types of movements. In this study, we tested the hypothesis that feedforward cardiovascular responses occur when a passive (imposed) 60° head-up tilt is anticipated, such that changes in heart rate and carotid artery blood flow (CBF) commence prior to the onset of the rotation. A light cue preceded head-up tilts by 10 sec, and heart rate and CBF were determined for 5-sec time periods prior to and during tilts...
January 2018: Physiological Reports
https://www.readbyqxmd.com/read/29327677/autologous-smooth-muscle-progenitor-cells-enhance-regeneration-of-tissue-engineered-bladder
#7
Liuhua Zhou, Jiadong Xia, Pengji Wang, Ruipeng Jia, Jun Hua Zheng, Xudong Yao, Yun Chen, Yutian Dai, Bin Yang
Tissue engineering techniques provide a great potential to de novo construct a histological bladder. Smooth muscle regeneration is extremely important for the functional recovery of engineered neo-bladder. However, many challenges remain for the use of bladder smooth muscle cells (SMCs) as the cell sources. Recent evidences showed that smooth muscle progenitor cells (SPCs) in the peripheral blood have the capacity of differentiating into SMCs, while their use for bladder regeneration hasn't yet been reported...
January 12, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29313031/direct-comparison-of-oligochaete-erythrocruorins-as-potential-blood-substitutes
#8
Devon Zimmerman, Matthew DiIusto, Jack Dienes, Osheiza Abdulmalik, Jacob J Elmer
While many blood substitutes are based on mammalian hemoglobins (e.g., human hemoglobin, HbA), the naturally extracellular hemoglobins of invertebrates (a.k.a. erythrocruorins, Ecs) are intriguing alternative oxygen carriers. Specifically, the erythrocruorin of Lumbricus terrestris has been shown to effectively deliver oxygen in mice and rats without the negative side effects observed with HbA. In this study, the properties of six oligochaete Ecs (Lumbricus terrestris, Eisenia hortensis, Eisenia fetida, Eisenia veneta, Eudrilus eugeniae, and Amynthas gracilis) were compared in vitro to identify the most promising blood substitute candidate(s)...
June 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/29310686/comparison-of-two-different-coagulation-algorithms-on-the-use-of-allogenic-blood-products-and-coagulation-factors-in-severely-injured-trauma-patients-a-retrospective-multicentre-observational-study
#9
Alexander Kaserer, Mattias Casutt, Kai Sprengel, Burkhardt Seifert, Donat R Spahn, Philipp Stein
BACKGROUND: At the University Hospital Zurich (USZ) and the Cantonal Hospital of Lucerne (LUKS) an individualized goal-directed coagulation and transfusion algorithm was introduced and implemented before 2012 (Coagulation algorithm of the USZ: USZ-Alg; of the LUKS: LUKS-Alg). Main differences between both algorithms are: 1) A target haematocrit-range of 0.21-0.24 (USZ-Alg) vs. a lower haematocrit limit only (LUKS-Alg). 2) Blind coagulation-package in selected cases (LUKS-Alg only). 3) Factor XIII substitution is considered earlier according to the USZ-Alg...
January 8, 2018: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
https://www.readbyqxmd.com/read/29298994/cost-effectiveness-of-hla-dqb1-hla-b-pharmacogenetic-guided-treatment-and-blood-monitoring-in-us-patients-taking-clozapine
#10
François R Girardin, Antoine Poncet, Arnaud Perrier, Nathalie Vernaz, Mark Pletscher, Caroline F Samer, Jeffrey A Lieberman, Jean Villard
Less than 1% of adult patients with schizophrenia taking clozapine develop agranulocytosis, and most of these cases occur within the first weeks of treatment. The human leukocyte antigen (HLA) region has been associated with genetic susceptibility to clozapine-induced agranulocytosis (single amino acid changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate the cost-effectiveness, from a healthcare provider's perspective, of an HLA genotype-guided approach in patients with treatment-resistant schizophrenia who were taking clozapine and to compare the results with the current absolute neutrophil count monitoring (ANCM) schemes used in the USA...
January 3, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29296927/abo-blood-group-a-transferases-catalyze-the-biosynthesis-of-fors-blood-group-fors1-antigen-upon-deletion-of-exon-3-or-4
#11
Miyako Yamamoto, Emili Cid, Fumiichiro Yamamoto
Evolutionarily related ABO and GBGT1 genes encode, respectively, A and B glycosyltransferases (AT and BT) and Forssman glycolipid synthase (FS), which catalyze the biosynthesis of A and B, and Forssman (FORS1) oligosaccharide antigens responsible for the ABO and FORS blood group systems. Humans are a Forssman antigen-negative species; however, rare individuals with Apae phenotype express FORS1 on their red blood cells. We previously demonstrated that the replacement of the LeuGlyGly tripeptide sequence at codons 266 to 268 of human AT with GBGT1-encoded FS-specific GlyGlyAla enabled the enzyme to produce FORS1 antigen, although the FS activity was weak...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296825/disease-severity-and-slower-psychomotor-speed-in-adults-with-sickle-cell-disease
#12
Dana R Jorgensen, Andrea Metti, Meryl A Butters, Joseph M Mettenburg, Caterina Rosano, Enrico M Novelli
Psychomotor slowing is common in children with sickle cell disease (SCD), but little is known about its severity in adults. We conducted a cross-sectional study to quantify psychomotor speed, measured with the digit symbol substitution test (DSST), in relationship with disease severity in adults with SCD attending an outpatient clinic (n = 88, age 36.3 years). Genotype was used to group patients in "severe" (homozygous for hemoglobin S or compound heterozygous with β0 thalassemia) or "moderate" groups (compound heterozygous for HbS, with either HbC or β+ thalassemia)...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296174/a-novel-thiazolidinediones-atzd2-rescues-memory-deficits-in-a-rat-model-of-type-2-diabetes-through-antioxidant-and-antiinflammation
#13
Xuan-Kang Wang, Ting Sun, Yu-Jiao Li, Yu-Hong Wang, Yan-Jiao Li, Liu-Di Yang, Dan Feng, Ming-Gao Zhao, Yu-Mei Wu
Type 2 diabetes (T2DM) has been associated with learning and memory impairment; however, drugs for diabetes could not prevent the development of cognitive decline in T2DM patients. In the present study, compounds derived from thiazolidinediones (TZD), a PPAR-γ agonist, were synthesized by conjuncting the alkyl-substituted benzimidazole group to TZD group (ATZDs). Based on the in vitro evaluation, the neuroprotection of ATZD2 was further investigated using a streptozotocin-induced T2DM rat model. Pharmacokinetic study showed that ATZD2 could pass the blood-brain barrier (BBB) while the rosiglitazone (RSG, the precursor compound of ATZD2) not...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288828/the-effects-of-strawberry-tree-water-leaf-extract-arbutin-and-hydroquinone-on-haematological-parameters-and-levels-of-primary-dna-damage-in-white-blood-cells-of-rats
#14
Karlo Jurica, Irena Brčić Karačonji, Nevenka Kopjar, Ana Shek-Vugrovečki, Tihana Cikač, Vesna Benković
ETHNOPHARMACOLOGICAL RELEVANCE: Strawberry tree (Arbutus unedo L., Ericaceae) leaves represent a potent source of biologically active compounds and have been used for a long to relieve symptoms of various health impairments and diseases. Two major compounds related to their beneficial activities in animals and humans are arbutin and hydroquinone. AIM OF THE STUDY: To establish potential benefit/risk ratio associated with daily oral administration of strawberry tree water leaf extract, arbutin and hydroquinone in doses expected to be non-toxic...
December 27, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29283210/ube2a-deficiency-in-two-siblings-a-novel-splicing-variant-inherited-from-a-maternal-germline-mosaicism
#15
Teresa Giugliano, Claudia Santoro, Annalaura Torella, Francesca Del Vecchio Blanco, Pia Bernardo, Vincenzo Nigro, Giulio Piluso
UBE2A deficiency is a syndromic condition of X-linked intellectual disability (ID) characterized by typical dysmorphic features that include synophrys, prominent supraorbital ridges, almond-shaped, and deep-set eyes, large ears, wide mouth, myxedematous appearance, hirsutism, micropenis, and onychodystrophy. To date, only seven familial UBE2A intragenic mutations and nine larger microdeletions encompassing UBE2A have been reported. Here, we describe two siblings with X-linked ID and typical clinical features of UBE2A deficiency caused by a novel hemizygous variant, identified by massively parallel sequencing of X-exome...
December 28, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29282103/within-host-evolution-of-enterococcus-faecium-during-longitudinal-carriage-and-transition-to-bloodstream-infection-in-immunocompromised-patients
#16
Danesh Moradigaravand, Theodore Gouliouris, Beth Blane, Plamena Naydenova, Catherine Ludden, Charles Crawley, Nicholas M Brown, M Estée Török, Julian Parkhill, Sharon J Peacock
BACKGROUND: Enterococcus faecium is a leading cause of hospital-acquired infection, particularly in the immunocompromised. Here, we use whole genome sequencing of E. faecium to study within-host evolution and the transition from gut carriage to invasive disease. METHODS: We isolated and sequenced 180 E. faecium from four immunocompromised patients who developed bloodstream infection during longitudinal surveillance of E. faecium in stool and their immediate environment...
December 27, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29250141/gynostemma-pentaphyllum-is-neuroprotective-in-a-rat-model-of-cardiopulmonary-resuscitation
#17
Gerburg Keilhoff, Torben Esser, Maximilian Titze, Uwe Ebmeyer, Lorenz Schild
Asphyxial cardiac arrest (ACA)-induced ischemia results in acute and delayed neuronal cell death. The early reperfusion phase is critical for the outcome. Intervention strategies directed to this period are promising to reduce ACA/resuscitation-dependent impairments. This study focused on the evaluation of the protective potential of an extract from Gynostemma pentaphyllum (GP), a plant used in traditional medicine with antioxidative, glucose lowering and neuroprotective activities, in an ACA rat model. We tested the following parameters: i) Basic systemic parameters such as pCO2 and blood glucose value within the first 30 min post-ACA; ii) mitochondrial response by determining activities of citrate synthase, respiratory chain complexes I + III and II + III, and the composition of cardiolipin 6 and 24 h post-ACA; iii) neuronal vitality of the CA1 hippocampal region by immunohistochemistry 24 h and 7 days post-ACA; and iv) cognitive function by a novel object recognition test 7 days post-ACA...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29249319/innate-immune-responses-of-equine-monocytes-cultured-in-equine-platelet-lysate
#18
Maria C Naskou, Natalie A Norton, Ian B Copland, Jacques Galipeau, John F Peroni
Platelet lysate (PL) has been extensively used for the laboratory expansion of human mesenchymal stem cells (MSC) in order to avoid fetal bovine serum (FBS) which has been associated with immune-mediated host reactions and transmission of bovine-origin microbial contaminants. Before suggesting the routine use of PL for MSC culture, we wanted to further investigate whether PL alone might trigger inflammatory responses when exposed to reactive white blood cells such as monocytes. Our objectives were to evaluate the inflammatory profile of equine monocytes cultured with equine PL (ePL) and to determine if ePL can modulate the expression of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated monocytes...
January 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29248465/disposition-of-%C3%AE-n-methylamino-l-alanine-l-bmaa-a-neurotoxin-in-rodents-following-a-single-or-repeated-oral-exposure
#19
Suramya Waidyanatha, Kristen Ryan, J Michael Sanders, Jacob D McDonald, Christopher J Wegerski, Melanie Doyle-Eisle, C Edwin Garner
β-N-methylamino-l-alanine (L-BMAA) is produced by cyanobacteria (blue-green algae). Human exposure to L-BMAA occurs via consumption of L-BMAA-contaminated water and food. It is speculated that exposure to L-BMAA, and subsequent brain accumulation, may contribute to an increased incidence of neurodegenerative diseases indicating the need to evaluate risk of L-BMAA exposure to humans. As an initial step in this process, we have evaluated disposition following a single or repeated gavage administration of 1, 10 or 100mg/kg [14C]L-BMAA in rats and mice...
December 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29248244/patency-and-in%C3%A2-vivo-compatibility-of-bacterial-nanocellulose-grafts-as-small-diameter-vascular-substitute
#20
Carolyn Weber, Stefanie Reinhardt, Kaveh Eghbalzadeh, Max Wacker, Maria Guschlbauer, Alexandra Maul, Anja Sterner-Kock, Thorsten Wahlers, Jens Wippermann, Max Scherner
OBJECTIVE: Despite the clinical success of large-diameter vascular grafts, synthetic grafts in small-diameter vessels are of limited use because of their poor patency rates. Previous experiments of our group provided evidence for good biocompatibility of bacterial nanocellulose (BNC) as a small-vessel graft in the carotid artery in sheep. However, the patency rate of our first-generation tubes after 3 months was only 50%. To advance our concept, we now used modified second-generation tubes with diminished wall thickness and a smoother inner surface to reduce the thrombogenic potential...
December 13, 2017: Journal of Vascular Surgery
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