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Clinical chemistry

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https://www.readbyqxmd.com/read/29149720/a-robust-strategy-for-preparation-of-sequential-stimuli-responsive-block-copolymer-prodrugs-via-thiolactone-chemistry-to-overcome-multiple-anticancer-drug-delivery-barriers
#1
Wendong Ke, Wei Yin, Zengshi Zha, Jean Felix Mukerabigwi, Weijian Chen, Yuheng Wang, Chuanxin He, Zhishen Ge
Block copolymer prodrugs (BCPs) have attracted considerable attentions in clinical translation of nanomedicine owing to their self-assembly into well-defined core-shell nanoparticles for improved pharmacokinetics, stability in blood circulation without drug leakage, and optimized biodistribution. However, a cascade of physiological barriers against specific delivery of drugs into tumor cells limit the final therapeutic efficacy. Herein, we report a robust and facile strategy based on thiolactone chemistry to fabricate well-defined BCPs with sequential tumor pH-promoted cellular internalization and intracellular stimuli-responsive drug release...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29147558/discovery-and-design-of-self-assembling-peptides
#2
REVIEW
Shuguang Zhang
Peptides are ubiquitous in nature and useful in many fields, from agriculture as pesticides, in medicine as antibacterial and antifungal drugs founded in the innate immune systems, to medicinal chemistry as hormones. However, the concept of peptides as materials was not recognized until 1990 when a self-assembling peptide as a repeating segment in a yeast protein was serendipitously discovered. Peptide materials are so called because they have bona fide materials property and are made from simple amino acids with well-ordered nanostructures under physiological conditions...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29146704/prospective-evaluation-of-kidney-disease-in-joubert-syndrome
#3
Leah R Fleming, Daniel A Doherty, Melissa A Parisi, Ian A Glass, Joy Bryant, Roxanne Fischer, Baris Turkbey, Peter Choyke, Kailash Daryanani, Meghana Vemulapalli, James C Mullikin, May Christine Malicdan, Thierry Vilboux, John A Sayer, William A Gahl, Meral Gunay-Aygun
BACKGROUND AND OBJECTIVES: Joubert syndrome is a genetically heterogeneous ciliopathy associated with >30 genes. The characteristics of kidney disease and genotype-phenotype correlations have not been evaluated in a large cohort at a single center. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated 97 individuals with Joubert syndrome at the National Institutes of Health Clinical Center using abdominal ultrasonography, blood and urine chemistries, and DNA sequencing...
November 16, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29146569/found-in-translation-how-preclinical-research-is-guiding-the-clinical-development-of-the-bcl2-selective-inhibitor-venetoclax
#4
REVIEW
Joel D Leverson, Deepak Sampath, Andrew J Souers, Saul H Rosenberg, Wayne J Fairbrother, Martine Amiot, Marina Konopleva, Anthony Letai
Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax...
November 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29145735/evaluation-of-performance-of-laboratories-and-manufacturers-within-the-framework-of-the-ifcc-model-for-quality-targets-of-hba1c
#5
Cas Weykamp, Carla Siebelder
HbA1c is a key parameter in diabetes management. For years the test has been used exclusively for monitoring of long-term diabetic control. However, due to improvement of the performance, HbA1c is considered more and more for diagnosis and screening. With this new application, quality demands further increase. A task force of the International Federation of Clinical Chemistry and Laboratory Medicine developed a model to set and evaluate quality targets for HbA1c. The model is based on the concept of total error and takes into account the major sources of analytical errors in the medical laboratory: bias and imprecision...
November 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/29142168/background-data-on-nod-shi-scid-il-2r%C3%AE-null-mice-nog-mice
#6
Kenichiro Kasahara, Yachiyo Fukunaga, Saori Igura, Rie Andoh, Tsubasa Saito, Isamu Suzuki, Hiroyuki Kanemitsu, Daisuke Suzuki, Ken Goto, Daichi Nakamura, Masahiro Mochizuki, Masahiko Yasuda, Ryo Inoue, Kazutoshi Tamura, Mariko Nagatani
To obtain background data of NOD/Shi-scid IL-2Rγ(null) (NOG) mice, severely immunedeficient mice, a total of 120 animals were examined at 7, 26 and 52 weeks-old (20 mice/sex/group). The survival rate at 52 weeks-old was 95% (19/20) in both sexes. Clinically, circling behavior in one direction along the cage wall was observed in males after 8 weeks and females after 47 weeks-old, and hunchback position was found in males after 32 weeks-old. Hematologically, lymphocyte count markedly decreased at all ages, while white blood cell count increased in several mice at 52 weeks-old...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29141148/plasmonically-enhanced-galactoxyloglucan-endowed-gold-nanoparticles-exposed-tumor-targeting-biodistribution-envisaged-in-a-surface-enhanced-raman-scattering-platform
#7
Manu M Joseph, Jyothi B Nair, Kaustabh Kumar Maiti, Sreelekha Therakathinal T
Biopolymer capped gold nanoparticles (AuNPs) were perceived for tracing biodistribution in a solid tumor mice through surface-enhanced Raman scattering (SERS) fingerprinting. In this strategy, a robust and ecofriendly green chemistry approach was adopted to construct galactoxyloglucan (PST001) endowed AuNPs (PST-GNPs) with cancer-cell-selective toxic nature and excellent biocompatibility. Plasmonically enhanced light scattering properties facilitated PST-GNPs to be a superior SERS substrate with high Raman signal enhancement...
November 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29140435/hmdb-4-0-the-human-metabolome-database-for-2018
#8
David S Wishart, Yannick Djoumbou Feunang, Ana Marcu, An Chi Guo, Kevin Liang, Rosa Vázquez-Fresno, Tanvir Sajed, Daniel Johnson, Carin Li, Naama Karu, Zinat Sayeeda, Elvis Lo, Nazanin Assempour, Mark Berjanskii, Sandeep Singhal, David Arndt, Yonjie Liang, Hasan Badran, Jason Grant, Arnau Serra-Cayuela, Yifeng Liu, Rupa Mandal, Vanessa Neveu, Allison Pon, Craig Knox, Michael Wilson, Claudine Manach, Augustin Scalbert
The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards...
November 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29140081/the-human-milk-glycome-as-a-defense-against-infectious-diseases-rationale-challenges-and-opportunities
#9
Kelly M Craft, Steven D Townsend
Each year over 3 million people die from infectious diseases with most of these deaths being poor and young children who live in low- and middle-income countries. Infectious diseases emerge for a multitude of reasons. On the social front, reasons include a breakdown of public health standards, international travel, and immigration (for financial, civil, and social reasons). At the molecular level, the modern rise of infectious diseases is tied to the juxtaposition of drug-resistant pathogens and a lack of new antimicrobials...
November 15, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29138215/physiology-undergraduate-degree-requirements-in-the-u-s
#10
Valerie S VanRyn, James M Poteracki, Erica A Wehrwein
Course-level learning objectives and core concepts for undergraduate physiology teaching exist. The next step is to consider how these resources fit into generalizable program-level guidelines for Bachelor of Science (BS) degrees in Physiology. In the absence of program-level guidelines for Physiology degree programs, we compiled a selective internal report to review degree requirements from 18 peer BS programs entitled "Physiology" in the United States (U.S.). There was a range of zero to three required semesters of math, physics, physics laboratory, general biology, biology laboratory, general chemistry, chemistry laboratory, organic chemistry, organic chemistry laboratory, biochemistry, biochemistry laboratory, anatomy, anatomy laboratory, core systems physiology, and physiology laboratory...
December 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/29133077/-chronic-kidney-failure-and-biotin-a-combination-inducing-unusual-results-in-thyroid-and-parathyroid-investigations-report-of-2-cases
#11
Miora Koloina Ranaivosoa, Sébastien Ganel, Arnaud Agin, Sarah Romain, Xavier Parent, Nathalie Reix
In clinical chemistry, many immunoassays apply biotin and streptavidin in the assay principle. Presence of high levels of biotin in patient samples can produce negative or positive interference depending on the assay format. In this study, we describe 2 clinical cases with chronic kidney failure and with unusual thyroid and parathyroid function test results due to biotin interference. We studied the impact of biotin levels on thyroid stimulating hormone (TSH), free thyroxine (T4L) and parathormone (PTH) results with a pool of sera loaded with several concentrations of biotin...
November 10, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29132988/safety-and-immunogenicity-of-a-novel-multiple-antigen-pneumococcal-vaccine-in-adults-a-phase-1-randomised-clinical-trial
#12
Claire Entwisle, Sue Hill, Yin Pang, Michael Joachim, Ann McIlgorm, Camilo Colaco, David Goldblatt, Polly De Gorguette D'Argoeuves, Chris Bailey
BACKGROUND: Pneumococcal vaccines, combining multiple protein antigens, provide an alternative approach to currently marketed vaccines and may provide broader protection against pneumococcal disease. This trial evaluated the safety and immunogenicity of a novel vaccine candidate PnuBioVax in healthy young adults. METHODS: In a Phase 1 double-blind study, 36 subjects (18-40 years) were randomised to receive 3 doses of PnuBioVax, 28 days apart, at one of three dose levels (50, 200, 500 µg) or placebo...
November 10, 2017: Vaccine
https://www.readbyqxmd.com/read/29131397/a-double-blind-placebo-controlled-multicenter-prospective-randomized-study-of-beraprost-sodium-treatment-for-cats-with-chronic-kidney-disease
#13
M Takenaka, A Iio, R Sato, T Sakamoto, H Kurumatani
BACKGROUND: Chronic kidney disease (CKD) is a common progressive and irreversible disease in cats. The efficacy and safety of beraprost sodium (BPS) in cats with CKD have not been evaluated. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy and safety of BPS in the treatment of cats with CKD, as compared to placebo. ANIMALS: Seventy-four client-owned cats with naturally occurring CKD. METHODS: Double-blind, placebo-controlled, multicenter, prospective, randomized trial...
November 13, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29130542/safety-evaluation-of-p-synephrine-following-15%C3%A2-days-of-oral-administration-to-healthy-subjects-a-clinical-study
#14
Mohd Shara, Sidney J Stohs, Mahmoud M Smadi
Extracts of bitter orange (BOE, Citrus aurantium L.) and its primary protoalkaloid p-synephrine are extensively consumed as dietary supplements. p-Synephrine is also present in foods and juices prepared from various Citrus species. The safety of p-synephrine has been questioned as a result of structural similarities with ephedrine. This study assessed the cardiovascular (stimulant) and hemodynamic effects of BOE (49 mg p-synephrine) daily given to 16 healthy subjects for 15 days in a placebo-controlled, cross-over, double-blinded study...
November 12, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29125739/yield-improvement-of-the-anti-mrsa-antibiotics-wap-8294a-by-crispr-dcas9-combined-with-refactoring-self-protection-genes-in-lysobacter-enzymogenes-oh11
#15
Lingjun Yu, Wei Su, Paul D Fey, Fengquan Liu, Liangcheng Du
The cyclic lipodepsipeptides WAP-8294A are antibiotics with potent activity against methicillin-resistant Staphylococcus aureus (MRSA). One member of this family, WAP-8294A2 (Lotilibcin), was in clinical trials due to its high activity and distinct chemistry. However, WAP-8294A compounds are produced in a very low yield by Lysobacter and only under very stringent conditions. Improving WAP-8294A yield has become very critical for research and application of these anti-MRSA compounds. Here, we report a strategy to increase WAP-8294A production...
November 10, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29124749/prediction-of-bleeding-and-thrombosis-by-standard-biochemical-coagulation-variables-in-haematological-intensive-care-patients
#16
L Russell, M B Madsen, M Dahl, P Kampmann, A Perner
PURPOSE: We assessed the value of standard biochemical coagulation parameters in predicting bleeding, thrombosis and mortality in adult Intensive Care Unit (ICU) patients with haematological malignancies. METHODS: We screened all patients with acute leukaemia and myelodysplastic syndrome admitted to a university hospital ICU during 2008-2012. Data were obtained from the clinical chemistry laboratory database and patient files. We graded bleeding according to the World Health Organisation (WHO)-system within 24-h, within 5-days and during the whole ICU stay...
November 9, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/29122981/in-situ-imaging-of-mitochondrial-translation-shows-weak-correlation-with-nucleoid-dna-intensity-and-no-suppression-during-mitosis
#17
Christopher Estell, Emmanouela Stamatidou, Sarah El-Messeiry, Andrew Hamilton
Although mitochondrial translation produces only 13 proteins, we show here how this can be labelled and detected in situ by fluorescence microscopy with a simple, rapid and inexpensive procedure using non-canonical amino acid labelling and click chemistry. This allows visualisation of the translational output in different mitochondria within a cell, their position within that cell and a comparison of mitochondrial translation between cells. Most highly translationally active mitochondria were closest to the nucleus but were also found at the distal end of long cellular projections...
November 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29119003/novel-associations-of-bile-acid-diarrhoea-with-fatty-liver-disease-and-gallstones-a-cohort-retrospective-analysis
#18
Richard N Appleby, Jonathan D Nolan, Ian M Johnston, Sanjeev S Pattni, Jessica Fox, Julian Rf Walters
Background: Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD. Methods: A cohort of patients with chronic diarrhoea who underwent (75)selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively...
2017: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/29118676/host-responses-to-concurrent-combined-injuries-in-non-human-primates
#19
Matthew J Bradley, Diego A Vicente, Benjamin A Bograd, Erin M Sanders, Crystal L Leonhardt, Eric A Elster, Thomas A Davis
Background: Multi-organ failure (MOF) following trauma remains a significant cause of morbidity and mortality related to a poorly understood abnormal inflammatory response. We characterized the inflammatory response in a non-human primate soft tissue injury and closed abdomen hemorrhage and sepsis model developed to assess realistic injury patterns and induce MOF. Methods: Adult male Mauritan Cynomolgus Macaques underwent laparoscopy to create a cecal perforation and non-anatomic liver resection along with a full-thickness flank soft tissue injury...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/29116596/antibody-drug-conjugates-for-the-treatment-of-solid-tumors-clinical-experience-and-latest-developments
#20
Aiko Nagayama, Leif W Ellisen, Bruce Chabner, Aditya Bardia
Antibody-drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-positive Hodgkin's lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2 (HER2)-positive breast cancer...
November 8, 2017: Targeted Oncology
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