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https://www.readbyqxmd.com/read/28430398/impact-of-acid-reducing-agents-on-the-pharmacokinetics-of-palbociclib-a-weak-base-with-ph-dependent-solubility-with-different-food-intake-conditions
#1
Wan Sun, Karen J Klamerus, Lisa M Yuhas, Sylvester Pawlak, Anna Plotka, Melissa O'Gorman, Leonid Kirkovsky, Maha Kosa, Diane Wang
Palbociclib free base capsule is a weak base drug with highly pH-dependent solubility. In vitro and in vivo studies evaluated the impact of acid-reducing agents on exposure of palbociclib and determined whether the impact, if any, can be mitigated by food. A drug-drug interaction study (study 1) was conducted first under fasted conditions and showed that coadministration of multiple doses of the proton-pump inhibitor rabeprazole substantially reduced palbociclib mean area under the concentration-time curve from time 0 to infinity and maximum observed plasma concentration by 62% and 80%, respectively...
April 21, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28425419/a-rare-bsep-mutation-associated-with-a-mild-form-of-progressive-familial-intrahepatic-cholestasis-type-2
#2
Orith Waisbourd-Zinman, Lea F Surrey, Anna E Schwartz, Pierre A Russo, Jessica Wen
Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2) is a rare cholestatic disorder diagnosed in infancy or childhood that can lead to severe hepatic fibrosis and liver failure. Mutations in the ABCB11 gene result in a deficiency of the bile salt export protein (BSEP) and accumulation of bile inside the hepatocytes. Hepatocellular carcinoma is another condition associated with severe forms of deletion mutations in the ABCB11 gene. Treatment options including ursodeoxycholic acid biliary diversion have mixed outcomes and some patients require liver transplantation...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28404070/pathophysiology-of-irritable-bowel-syndrome
#3
REVIEW
Gerald J Holtmann, Alexander C Ford, Nicholas J Talley
Traditionally, irritable bowel syndrome has been considered to be a disorder with no known underlying structural or biochemical explanation, but this concept is likely to be outdated. In this Review we challenge the widely accepted view that irritable bowel syndrome is an unexplained brain-gut disorder. There is epidemiological evidence that, in a major subset of patients, gastrointestinal symptoms arise first and only later do incident mood disorders occur. Additionally, possible mechanisms for gut-brain dysfunction have been identified, suggesting primary gut disturbances might be the underlying cause in a subgroup...
October 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28392238/organochloride-pesticides-modulated-gut-microbiota-and-influenced-bile-acid-metabolism-in-mice
#4
Qian Liu, Wentao Shao, Chunlan Zhang, Cheng Xu, Qihan Wang, Hui Liu, Haidong Sun, Zhaoyan Jiang, Aihua Gu
Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing...
April 6, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28385542/model-systems-for-studying-the-role-of-canalicular-efflux-transporters-in-drug-induced-cholestatic-liver-disease
#5
REVIEW
Bruno Stieger, Zainab M Mahdi
Bile formation is a key function of the liver. Disturbance of bile flow may lead to liver disease and is called cholestasis. Cholestasis may be inherited such as for example in progressive familial intrahepatic cholestasis or acquired, such as for example by drug-mediated inhibition of bile salt export from hepatocytes into the canaliculi. The key transport system for exporting bile salts into the canaliculi is the bile salt export pump. Inhibition of the bile salt export pump by drugs is a well-established cause of drug-induced cholestasis...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28385289/use-of-a-novel-docosahexaenoic-acid-formulation-vs-control-in-a-neonatal-porcine-model-of-short-bowel-syndrome-leads-to-greater-intestinal-absorption-and-higher-systemic-levels-of-dha
#6
Camilia R Martin, Barbara Stoll, Joanne Cluette-Brown, Adesola C Akinkuotu, Oluyinka O Olutoye, Kathleen M Gura, Pratibha Singh, Munir M Zaman, Michael C Perillo, Mark Puder, Steven D Freedman, Doug Burrin
Infants with short bowel syndrome (SBS) are at high risk for malabsorption, malnutrition, and failure to thrive. The objective of this study was to evaluate in a porcine model of SBS, the systemic absorption of a novel enteral Docosahexaenoic acid (DHA) formulation that forms micelles independent of bile salts (DHA-ALT®). We hypothesized that enteral delivery of DHA-ALT® would result in higher blood levels of DHA compared to a control DHA preparation due to improved intestinal absorption. SBS was induced in term piglets through a 75% mid-jejunoileal resection and the piglets randomized to either DHA-ALT® or control DHA formulation (N=5 per group) for 4 postoperative days...
March 2017: Nutrition Research
https://www.readbyqxmd.com/read/28384537/characterization-of-colloidal-structures-during-intestinal-lipolysis-using-small-angle-neutron-scattering
#7
Oljora Rezhdo, Selena Di Maio, Peisi Le, Kenneth C Littrell, Rebecca L Carrier, Sow-Hsin Chen
HYPOTHESIS: Bile micelles are thought to mediate intestinal absorption, in part by providing a phase into which compounds can partition. Solubilizing capacity of bile micelles is enhanced during the digestion of fat rich food. We hypothesized that the intestinal digestion of triglycerides causes an increase in volume of micelles that can be quantitatively monitored over the course of digestion using small-angle neutron scattering (SANS), and that SANS can enable evaluation of the contribution of each of the components present during digestion to the size of micelles...
August 1, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28384222/functional-studies-of-e-faecalis-rnase-j2-and-its-role-in-virulence-and-fitness
#8
Peng Gao, Kenneth L Pinkston, Agathe Bourgogne, Barbara E Murray, Ambro van Hoof, Barrett R Harvey
Post-transcriptional control provides bacterial pathogens a method by which they can rapidly adapt to environmental change. Dual exo- and endonucleolytic activities of RNase J enzymes contribute to Gram-positive RNA processing and decay. First discovered in Bacillus subtilis, RNase J1 plays a key role in mRNA maturation and degradation, while the function of the paralogue RNase J2 is largely unknown. Previously, we discovered that deletion of the Enterococcus faecalis rnjB gene significantly attenuates expression of a major virulence factor involved in enterococcal pathogenesis, the Ebp pili...
2017: PloS One
https://www.readbyqxmd.com/read/28384209/analyses-of-the-probiotic-property-and-stress-resistance-related-genes-of-lactococcus-lactis-subsp-lactis-ncdo-2118-through-comparative-genomics-and-in-vitro-assays
#9
Letícia C Oliveira, Tessália D L Saraiva, Wanderson M Silva, Ulisses P Pereira, Bruno C Campos, Leandro J Benevides, Flávia S Rocha, Henrique C P Figueiredo, Vasco Azevedo, Siomar C Soares
Lactococcus lactis subsp. lactis NCDO 2118 was recently reported to alleviate colitis symptoms via its anti-inflammatory and immunomodulatory activities, which are exerted by exported proteins that are not produced by L. lactis subsp. lactis IL1403. Here, we used in vitro and in silico approaches to characterize the genomic structure, the safety aspects, and the immunomodulatory activity of this strain. Through comparative genomics, we identified genomic islands, phage regions, bile salt and acid stress resistance genes, bacteriocins, adhesion-related and antibiotic resistance genes, and genes encoding proteins that are putatively secreted, expressed in vitro and absent from IL1403...
2017: PloS One
https://www.readbyqxmd.com/read/28378299/activity-guided-separation-and-characterization-of-new-halocin-ha3-from-fermented-broth-of-haloferax-larsenii-ha3
#10
Vijay Kumar, Santosh Kumar Tiwari
Haloferax larsenii HA3 was able to grow optimally in HS medium containing 15% NaCl, at pH 7.2 and 42 °C in aerobic conditions. Strain HA3 was found to be round shape, Gram-negative, catalase-positive, sensitive to bile acid, and resistant to chloramphenicol, and could not utilize arginine. The lipid profile revealed the presence of glycerol diether moiety (GDEM) suggesting Haloarchaea characteristics. Phylogenetic analysis based on 16S rRNA gene sequence similarities showed that it was closely related to H...
April 4, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/28378090/solute-carrier-organic-anion-transporter-family-member-4a1-slco4a1-as-a-prognosis-marker-of-colorectal-cancer
#11
Myung Jin Ban, Sang Hee Ji, Chi-Kyu Lee, Sang Byung Bae, Han Jo Kim, Tae Sung Ahn, Moon Soo Lee, Moo-Jun Baek, Dongjun Jeong
PURPOSE: Solute carrier organic anion transporter family member 4A1 (SLCO4A1) is involved in the transport of various compounds, including sugars, bile salts, organic acids, metal ions, amine compounds, and estrogen. SLCO4A1 is highly expressed in several cancers and a gender bias has been observed in colorectal cancer (CRC). We investigated SLCO4A1 expression, its prognostic value in patients with CRC, and its role in CRC cell proliferation and metastasis. METHODS: SLCO4A1 expression was assessed by immunohistochemistry (IHC) on specimens from 84 patients with CRC...
April 4, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28369588/in-vitro-drug-induced-liver-injury-prediction-criteria-optimization-of-efflux-transporter-ic50-and-physicochemical-properties
#12
Robert W Yucha, Kan He, Qin Shi, Lining Cai, Yukie Nakashita, Cindy Q Xia, Mingxiang Liao
Drug-induced liver injury (DILI) is a severe drug adverse response, which cannot always be reliably predicted in preclinical or clinical studies. Lack of observation of DILI during preclinical and clinical drug development has led to DILI being a leading cause of drug withdrawal from the market. As DILI is potentially fatal, pharmaceutical companies have been developing in vitro tools to screen for potential liver injury. Screens for physicochemical properties, mitochondrial function, and transport protein inhibition have all been employed to varying degrees of success...
March 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28368001/genetic-and-proteomic-characterization-of-bile-salt-export-pump-bsep-in-snake-liver
#13
Xinle Tan, Fei Gao, Hexiu Su, Yajun Gong, Jie Zhang, Mitchell A Sullivan, Jiachun Chen
Snake gallbladder, a traditional Chinese medicine, has been believed in various Asian countries to improve visual acuity and alleviate rheumatism. Bile acids, a major component of the gallbladder, are toxic to the liver and kidney in humans and animals due to its detergent effects, while also exhibiting therapeutic effects due to an increase in the gallbladder contractions of muscle strips in patients with cholesterol gallstones. Secretion of bile acids in human and mammals depends on the bile salt export pump (BSEP), a liver-specific adenosine triphosphate (ATP)-binding cassette transporter encoded by ABCB11...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365295/in-vitro-and-in-vivo-performance-of-monoacyl-phospholipid-based-self-emulsifying-drug-delivery-systems
#14
Thuy Tran, Scheyla D V S Siqueira, Heinz Amenitsch, Anette Müllertz, Thomas Rades
This study investigates the effect of monoacyl phospholipid incorporation on the in vitro and in vivo performance of self-emulsifying drug delivery systems (SEDDS). Monoacyl phosphatidylcholine (Lipoid S LPC 80 (LPC)) was incorporated into four different fenofibrate (FF)-loaded long-chain SEDDS to investigate the impact of LPC on the emulsion droplet size, extent of digestion, colloidal structure evolution and drug precipitation during in vitro lipolysis simulating human conditions and drug bioavailability in a rat model...
March 30, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28363127/tissue-uptake-distribution-and-excretion-of-brevetoxin-3-after-oral-and-intratracheal-exposure-in-the-freshwater-turtle-trachemys-scripta-and-the-diamondback-terrapin-malaclemys-terrapin
#15
Courtney C Cocilova, Leanne J Flewelling, Gregory D Bossart, April A Granholm, Sarah L Milton
Harmful algal blooms (HABs) occur nearly annually off the west coast of Florida and can impact both humans and wildlife, resulting in morbidity and increased mortality of marine animals including sea turtles. The key organism in Florida red tides is the dinoflagellate Karenia brevis that produces a suite of potent neurotoxins referred to as the brevetoxins (PbTx). Despite recent mortality events and rehabilitation efforts, still little is known about how the toxin directly impacts sea turtles, as they are not amenable to experimentation and what is known about toxin levels and distribution comes primarily from post-mortem data...
March 7, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28348056/analysis-of-shigella-flexneri-resistance-biofilm-formation-and-transcriptional-profile-in-response-to-bile-salts
#16
Kourtney P Nickerson, Rachael B Chanin, Jeticia R Sistrunk, David A Rasko, Peter J Fink, Eileen M Barry, James P Nataro, Christina S Faherty
The Shigella species cause millions of cases of watery or bloody diarrhea each year, mostly in children in developing countries. While many aspects of Shigella colonic cell invasion are known, crucial gaps in knowledge remain regarding how the bacteria survive, transit, and regulate gene expression prior to infection. In this study, we define mechanisms of bile salts resistance and build on previous research highlighting induced virulence in S. flexneri strain 2457T following bile salts exposure. Typical growth patterns were observed within the physiological range of bile salts; however, growth was inhibited at higher concentrations...
March 27, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28341748/drug-induced-liver-injury-recent-advances-in-diagnosis-and-risk-assessment
#17
REVIEW
Gerd A Kullak-Ublick, Raul J Andrade, Michael Merz, Peter End, Andreas Benesic, Alexander L Gerbes, Guruprasad P Aithal
Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. Although currently used liver parameters are sensitive in detecting DILI, they are neither specific nor able to predict the patient's subsequent clinical course. Genetic risk assessment is useful mainly due to its high negative predictive value, with several human leucocyte antigen alleles being associated with DILI...
March 23, 2017: Gut
https://www.readbyqxmd.com/read/28331225/cholesterol-attenuates-cytoprotective-effects-of-phosphatidylcholine-against-bile-salts
#18
Yoshito Ikeda, Shin-Ya Morita, Tomohiro Terada
Bile salts have potent detergent properties and damaging effects on cell membranes, leading to liver injury. However, the molecular mechanisms for the protection of hepatocytes against bile salts are not fully understood. In this study, we demonstrated that the cytotoxicity of nine human major bile salts to HepG2 cells and primary human hepatocytes was prevented by phosphatidylcholine (PC). In contrast, cholesterol had no direct cytotoxic effects but suppressed the cytoprotective effects of PC. PC reduced the cell-association of bile salt, which was reversed by cholesterol...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331163/in-vitro-evaluation-of-candidate-bacillus-spp-for-animal-feed
#19
Sirima Mingmongkolchai, Watanalai Panbangred
The aim of this study was to select aerobic spore-formers for animal feed based on their in vitro probiotic potential, including their enzyme-producing ability and safety assessment. Seven isolates out of 187 spore-forming bacteria were selected for their ability to produce cellulase (89.21-1668.32 U/ml), xylanase (1399.68-4351.10 U/ml), and phytase (2.72-28.70 U/ml). Among seven isolates, five had activities towards a broad range of p-nitrophenyl esters with acyl chain lengths from C2 to C12. The probiotic properties of all selected isolates varied with respect to their acid and bile salt tolerance under simulated gastrointestinal tract (GIT) conditions, and their adherence ability to human intestinal cell lines (Caco-2 and HT-29)...
March 22, 2017: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/28324838/influence-of-multi-walled-carbon-nanotubes-on-the-effects-of-roxithromycin-in-crucian-carp-carassius-auratus-in-the-presence-of-natural-organic-matter
#20
Zhenhua Yan, Guanghua Lu, Hongwei Sun, Binni Ma
Carbon nanotubes are increasingly entering the aquatic environment and may interact with other co-existing contaminants, such as antibiotics. However, whether these interactions may affect their bioavailability in aquatic organisms is the subject of considerable debate. The primary objective of this study was to assess the risks arising from the coexistence of roxithromycin (ROX) and multi-walled carbon nanotubes (MWCNTs) in waters containing natural organic matter (NOM), focusing on the distribution and bioaccumulation of ROX in crucian carp (Carassius auratus), and the related biochemical status...
March 11, 2017: Chemosphere
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