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https://www.readbyqxmd.com/read/28719906/a-common-ancestral-asn242ser-mutation-in-tmem67-identified-in-multiple-iranian-families-with-joubert-syndrome
#1
MohammadReza Dehghani, Majid Mojarad, Ehsan Ghayoor Karimiani, Mohammad Yahya Vahidi Mehrjardi, Afsaneh Sahebalzamani, Farah Ashrafzadeh, Mehran Beiraghi Toosi, Atiyeh Eslahi, Najmeh Ahangari, Seyed Mojtaba Yassini, Afsaneh Hassanbeigi, Azam Rasti, Seyed Mehdi Kalantar, Reza Maroofian
BACKGROUND: Joubert syndrome (JS) is a clinically and genetically heterogeneous group of rare neurodevelopmental disorder characterised by peculiar midbrain-hindbrain malformation, known as the "molar tooth" sign. JS can manifest a broad range of signs and symptoms. The most common features of JS are hypotonia, ataxia, developmental delay/intellectual disability, abnormal eye movements, and neonatal breathing abnormalities. To date, 29 genes have been shown to cause JS. METHODS: We employed whole-genome single nucleotide polymorphism genotyping in a group of Iranian families with JS and Sanger sequencing of a known mutation associated with JS located in a single homozygous regions shared by affected members of the families...
July 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28719882/antileishmanial-activity-and-tubulin-polymerization-inhibition-of-podophyllotoxin-derivatives-on-leishmania-infantum
#2
José Miguel Escudero-Martínez, Yolanda Pérez-Pertejo, Rosa M Reguera, María Ángeles Castro, María Victoria Rojo, Carolina Santiago, Andrés Abad, Pablo Anselmo García, José Luis López-Pérez, Arturo San Feliciano, Rafael Balaña-Fouce
Leishmania microtubules play an important role not only in cell division, but also in keeping the shape of the parasite and motility of its free-living stages. Microtubules result from the self-assembly of alpha and beta tubulins, two phylogenetically conserved and very abundant eukaryotic proteins in kinetoplastids. The colchicine binding domain has inspired the discovery and development of several drugs currently in clinical use against parasites. However, this domain is less conserved in kinetoplastids and may be selectively targeted by new compounds...
June 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28719293/case-report-clinical-features-of-a-case-of-suspected-borrelia-miyamotoi-disease-in-hokkaido-japan
#3
Kimiaki Yamano, Takuya Ito, Kaori Kiyanagi, Hirotaka Yamazaki, Mutsubu Sugawara, Takashige Saito, Norio Ohashi, Aya Zamoto-Niikura, Kozue Sato, Hiroki Kawabata
We herein report a case of suspected Borrelia miyamotoi disease in Hokkaido, Japan. The patient complained of lassitude, arthralgia, and high fever after a tick bite. Furthermore, at the time of consultation, the patient exhibited momentary loss of consciousness and low blood pressure. Laboratory tests revealed elevation of liver enzymes, thrombocytopenia, and increased C-reactive protein. Seroconversion to B. miyamotoi glycerophosphoryl diester phosphodiesterase antigen suggested the patient was infected with a relapsing fever group Borrelia species...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28719070/sirtuin-1-attenuates-inflammation-and-hepatocellular-damage-in-liver-transplant-ischemia-reperfusion-from-mouse-to-human
#4
Kojiro Nakamura, Shoichi Kageyama, Bibo Ke, Takehiro Fujii, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI), an inevitable antigen-independent inflammation response in cadaveric liver transplantation, correlates with poor early graft function, rejection episodes, and contributes to donor organ shortage. Sirtuin 1 (SIRT1) is a histone deacetylase which may regulate inflammatory cell activity and manage liver function in IRI, though its functional role and clinical relevance remains to be elucidated. We investigated the efficacy of SIRT1 activation in murine liver IRI model and verified the concept of putative SIRT1-mediated hepatoprotection in clinical liver transplantation...
July 18, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28719006/relative-exchangeable-copper-a-valuable-tool-for-the-diagnosis-of-wilson-disease
#5
Olivier Guillaud, Anne-Sophie Brunet, Isabelle Mallet, Jérôme Dumortier, Martine Pelosse, Sophie Heissat, Christine Rivet, Alain Lachaux, Muriel Bost
BACKGROUND & AIMS: Measuring of the relative exchangeable copper seems to be a promising tool for the diagnosis of Wilson disease. The aim of our study is to determine the performance of REC for the diagnosis of Wilson disease in a population of patients with chronic liver diseases. METHODS: Measuring of exchangeable serum copper levels and relative exchangeable copper was performed in a group of Wilson disease patients at diagnosis or at clinical deterioration because of non-compliance (group 1, n=9), a group of stable WD patients (group 2, n=40), and 2 groups of patients (adult and pediatric) followed for non-Wilsonian liver diseases (group 3, n=103 and group 4, n=49, respectively)...
July 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28718980/an-endogenous-dna-adduct-as-a-prognostic-biomarker-for-hepatocarcinogenesis-and-its-prevention-by-theaphenon-e-in-mice
#6
Ying Fu, Shana Silverstein, Justine N McCutcheon, Marcin Dyba, Raghu G Nath, Monika Aggarwal, Heidi Coia, Angela Bai, Jishen Pan, Jiji Jiang, Bhaskar Kallakury, Hongkun Wang, Yu-Wen Zhang, Giuseppe Giaccone, Aiwu Ruth He, Fung-Lung Chung
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, mainly because of its poor prognosis. A valid mechanism-based prognostic biomarker is urgently needed. γ-hydroxy-1,N(2) -propanodeoxyguanosine (γ-OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation (LPO). We examined the relationship of γ-OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in the Xeroderma pigmentosum group A knockout mice (Xpa(-/-) ), and the diethylnitrosamine (DEN)-injected mice, both prone to HCC development...
July 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28718808/beta-palmitate-improves-bone-length-and-quality-during-catch-up-growth-in-young-rats
#7
Meytal Bar-Maisels, Yankel Gabet, Raanan Shamir, Sahar Hiram-Bab, Metsada Pasmanik-Chor, Moshe Phillip, Fabiana Bar-Yoseph, Galia Gat-Yablonski
Palmitic acid (PA) is the most abundant saturated fatty acid in human milk, where it is heavily concentrated in the sn-2-position (termed beta palmitate, BPA) and as such is conserved in all women, regardless of their diet or ethnicity, indicating its physiological and metabolic importance. We hypothesized that BPA improves the efficiency of nutrition-induced catch up growth as compared to sn-1,3 PA, which is present in vegetable oil. Pre-pubertal male rats were subjected to a 17 days food restriction followed by re-feeding for nine days with 1,3 PA or BPA-containing diets...
July 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28718696/tumor-induced-disorder-of-iron-metabolism-in-major-organs-a-new-insight-from-chemical-speciation-of-iron
#8
Rujie Chen, Guangcun Chen
Objective To investigate the evolution of iron speciation in major organs of tumor-bearing mice and its role in cancer formation and cancer-associated complications. Methods The concentration and chemical speciation of iron in the spleen, liver, lung, kidney, heart, blood, muscle, and tumor tissue of healthy mice and tumor-bearing mice were studied by synchrotron radiation-based total reflection X-ray fluorescence spectrometry (SR-TXRF) coupled with X-ray absorption spectroscopy (XAS). Results The TXRF and XAS results showed that the iron content, especially the ferritin content, significantly decreased in the blood and spleen but significantly increased in the liver, lung, and muscle of mice after tumor implantation...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28718084/pancreatic-neuroendocrine-tumor-producing-insulin-and-vasopressin
#9
Omalkhaire M Alshaikh, Ju-Yoon Yoon, Bryan A Chan, Monika K Krzyzanowska, Jagdish Butany, Sylvia L Asa, Shereen Ezzat
The objective of the study is to report a rare case of pancreatic neuroendocrine tumor (pNET) producing insulin and vasopressin. We describe the clinical presentation and management of a metastatic pNET with refractory hypoglycemia and progressive severe hyponatremia. A 52-year-old patient had abdominal pain leading to the diagnosis of a tumor that was initially presumed to be splenic in origin. Investigations ultimately identified a pancreatic mass that on biopsy proved to be a pNET. Eventually, he developed extensive liver metastases, and with tumor progression, he manifested hypoglycemia and severe hyponatremia...
July 17, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28718042/contrast-enhanced-ultrasound-for-focal-liver-lesions-how-accurate-is-it
#10
Richard G Barr
With the recent FDA approval for characterization of focal liver lesions (FLL) in both pediatric and adult patients using Lumason (sulfur hexafluoride microbubbles), increased use of ultrasound contrast for routine clinical use is expected. This agent has been available for many years in Europe and Asia, and a large body of literature is available regarding the sensitivity and specificity of this agent. In addition, a few studies have directly compared CEUS to CECT and CEMRI for the characterization of focal liver lesions...
July 17, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28717664/genetic-variation-spectrum-in-atp7b-gene-identified-in-latvian-patients-with-wilson-disease
#11
Agnese Zarina, Ieva Tolmane, Madara Kreile, Aleksandrs Chernushenko, Gunta Cernevska, Ieva Pukite, Ieva Micule, Zita Krumina, Astrida Krumina, Baiba Rozentale, Linda Piekuse
BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by allelic variants in ATP7B gene. More than 500 distinct variants have been reported, the most common WD causing allelic variant in the patients from Central, Eastern, and Northern Europe is H1069Q. METHODS: All Latvian patients with clinically confirmed WD were screened for the most common mutation p.H1069Q by PCR Bi-PASA method. Direct DNA sequencing of gene ATP7B (all 21 exons) was performed for the patients with WD symptoms, being either heterozygous for H1069Q or without it on any allele...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28717121/impact-of-doppler-ultrasound-on-diagnosis-and-therapy-control-of-lienalis-steal-syndrome-after-liver-transplantation
#12
Eva M Teegen, Timm Denecke, Rosa B Schmuck, Robert Öllinger, Dominik Geisel, Johann Pratschke, Sascha S Chopra
BACKGROUND Lienalis steal syndrome is a rare complication after orthotopic liver transplantation leading to severe complications. Routine duplex sonography allows early and safe detection of lienalis steal syndrome and secondarily helps to monitor the outcome by evaluating the hemodynamics. MATERIAL AND METHODS This analysis included eight patients who after orthotopic liver transplantation needed splenic artery embolization due to lienalis steal syndrome. Lienalis steal syndrome was assumed in case of elevated transaminases, bilirubinemia or persistent ascites, and the absence of further pathologies...
July 18, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28717109/utility-of-human-hepatocyte-spheroids-without-feeder-cells-for-evaluation-of-hepatotoxicity
#13
Takuo Ogihara, Hiroshi Arakawa, Tomoko Jomura, Yoko Idota, Satoshi Koyama, Kentaro Yano, Hajime Kojima
We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717107/human-plasma-and-urinary-metabolic-profiles-of-trimethylamine-and-trimethylamine-n-oxide-extrapolated-using-a-simple-physiologically-based-pharmacokinetic-model
#14
Makiko Shimizu, Hiroshi Yamazaki
Trimethylamine, a dietary- and medicinal carnitine-derived amine, is extensively metabolized by liver to non-malodorous trimethylamine N-oxide. Although trimethylamine and trimethylamine N-oxide under daily dietary consumption or carnitine treatment are generally regarded as nontoxic, they have been, and remain, of toxicological and clinical interest because of their potential association with atherosclerosis. The aim of the current study was to model the pharmacokinetics of trimethylamine after oral administration of trimethylamine in humans and compare the results with reported measured values...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717105/ephedrine-induced-mitophagy-via-oxidative-stress-in-human-hepatic-stellate-cells
#15
Ah Young Lee, Yoonjeong Jang, Seong-Ho Hong, Seung-Hee Chang, Sungjin Park, Sanghwa Kim, Kyung-Sun Kang, Ji-Eun Kim, Myung-Haing Cho
The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717038/a-human-biofilm-disrupting-monoclonal-antibody-potentiates-antibiotic-efficacy-in-rodent-models-of-both-staphylococcus-aureus-and-acinetobacter-baumannii-infections
#16
Yan Q Xiong, Angeles Estellés, L Li, W Abdelhady, R Gonzales, Arnold S Bayer, Edgar Tenorio, Anton Leighton, Stefan Ryser, Lawrence M Kauvar
Many serious bacterial infections are antibiotic-refractory due to biofilm formation. A key structural component of biofilm is extracellular DNA which is stabilized by bacterial proteins, including those from the DNABII family. TRL1068 is a high affinity human monoclonal antibody against a DNABII epitope conserved across both gram-positive and gram-negative bacterial species. In the current study, the efficacy of TRL1068 for disruption of biofilm was demonstrated in vitro in the absence of antibiotics by scanning electron microscopy...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28716728/cytochrome-p450-3a-selectively-affects-the-pharmacokinetic-interaction-between-erlotinib-and-docetaxel-in-rats
#17
Xuan Qin, Jian Lu, Peili Wang, Peipei Xu, Mingyao Liu, Xin Wang
Erlotinib as a first-line drug is used in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations, while resistance to this drug will occur after several years of treatment. Therefore, the microtubule disturber docetaxel is introduced as combined regimen in clinical trials. This report investigated the potentials and mechanisms of drug-drug interaction (DDI) between erlotinib and docetaxel using wild type (WT) and Cyp3a1/2 knockout (KO) rats. The erlotinib O-demethylation and docetaxel hydroxylation reactions in the absence or the presence of another drug were analyzed in vitro via the assay of rat liver microsomes...
July 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28716239/acquired-transthyretin-amyloidosis-after-domino-liver-transplant-phenotypic-correlation-implication-of-liver-retransplantation
#18
Eli Muchtar, Martha Grogan, Surendra Dasari, Paul J Kurtin, Morie A Gertz
Reports of acquired ATTRm in domino liver transplant (DLT) recipients are infrequent and the approach to management is unknown. We describe two patients, an inherited ATTRm patient who underwent liver transplant and his liver recipient who developed acquired ATTRm 8years following transplantation. The clinical manifestations of amyloidosis were similar between patients and consisted of peripheral neuropathy, diarrhea and weight loss. Following liver transplantation, the DLT donor went into remission for 4years, but eventually progressed and died...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28716104/evaluating-the-potential-of-gold-silver-and-silica-nanoparticles-to-saturate-mononuclear-phagocytic-system-tissues-under-repeat-dosing-conditions
#19
James L Weaver, Grainne A Tobin, Taylor Ingle, Simona Bancos, David Stevens, Rodney Rouse, Kristina E Howard, David Goodwin, Alan Knapton, Xiaohong Li, Katherine Shea, Sharron Stewart, Lin Xu, Peter L Goering, Qin Zhang, Paul C Howard, Jessie Collins, Saeed Khan, Kidon Sung, Katherine M Tyner
BACKGROUND: As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. This study was designed to evaluate whether gold (10 nm), silver (50 nm), or silica (10 nm) nanoparticles administered intravenously to mice for up to 8 weeks at doses known to be sub-toxic (non-toxic at single acute or repeat dosing levels) and clinically relevant could produce significant bioaccumulation in liver and spleen macrophages...
July 17, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28716095/development-of-real-time-and-lateral-flow-dipstick-recombinase-polymerase-amplification-assays-for-rapid-detection-of-goatpox-virus-and-sheeppox-virus
#20
Yang Yang, Xiaodong Qin, Xiangle Zhang, Zhixun Zhao, Wei Zhang, Xueliang Zhu, Guozheng Cong, Yanmin Li, Zhidong Zhang
BACKGROUND: Goatpox virus (GTPV) and sheeppox virus (SPPV), which belong to the Capripoxvirus (CaPV), are economically important pathogens of small ruminants. Therefore, a sensitive, specific and rapid diagnostic assay for detection of GTPV and SPPV is necessary to accurately and promptly control these diseases. METHODS: Recombinase polymerase amplification (RPA) assays combined with a real-time fluorescent detection (real-time RPA assay) and lateral flow dipstick (RPA LFD assay) were developed targeting the CaPV G-protein-coupled chemokine receptor (GPCR) gene, respectively...
July 17, 2017: Virology Journal
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