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https://www.readbyqxmd.com/read/28807919/drug-susceptibility-and-replicative-capacity-of-multi-drug-resistant-recombinant-human-cytomegalovirus-harboring-mutations-in-ul56-and-ul54-genes
#1
Jocelyne Piret, Nathalie Goyette, Guy Boivin
Letermovir is an investigational antiviral agent with a novel mechanism of action involving the viral terminase (pUL56). We evaluated the impact of V236M mutation in UL56 gene alone and combined with E756K mutation in UL54 gene on drug susceptibility and viral replicative capacity of recombinant human cytomegalovirus. The double mutant exhibited at least borderline resistance to all antivirals tested (ganciclovir, foscarnet, cidofovir, brincidofovir and letermovir) and replicated less efficiently than the wild-type virus in vitro...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28783148/clinical-characteristics-and-outcome-of-human-herpesvirus-6-encephalitis-after-allogeneic-hematopoietic-stem-cell-transplantation
#2
M Ogata, K Oshima, T Ikebe, K Takano, H Kanamori, T Kondo, Y Ueda, T Mori, H Hashimoto, H Ogawa, T Eto, T Ueki, T Miyamoto, T Ichinohe, Y Atsuta, T Fukuda
In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11...
August 7, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28768993/molecular-basis-of-nucleobase-transport-systems-in-mammals
#3
Katsuhisa Inoue
Nucleobases are water-soluble compounds that need specific transporters to cross biological membranes. Cumulative evidence based on studies using animal tissues and cells indicates that the carrier-mediated transport systems for purine and pyrimidine nucleobases can be classified into the following two types: concentrative transport systems that mediate nucleobase transport depending on the sodium ion concentration gradient; and other systems that mediate facilitated diffusion depending on the concentration gradient of the substrate...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28763428/cmv-infection-in-pediatric-severe-ulcerative-colitis-a-multicenter-study-from-the-pediatric-ibd-porto-group-of-espghan
#4
Shlomi Cohen, Christine Martinez-Vinson, Marina Aloi, Dan Turner, Amit Assa, Lissy de Ridder, Victorien M Wolters, Tim de Meij, Patrizia Alvisi, Jiri Bronsky, Uri Kopylov
BACKGROUND: Data on the clinical course and outcomes of pediatric patients with cytomegalovirus (CMV) infection complicating acute severe ulcerative colitis (ASC) are very limited. The aim of our study was to compare outcomes of children with ASC who were CMV-positive or CMV-negative. METHODS: This was a multicenter retrospective case-controlled study, from centers affiliated with the Pediatric IBD Porto Group of ESPGHAN. We included CMV -positive children hospitalized for ASC and compared their colectomy rate during hospitalization and up to 1 year thereafter, matched with CMV-negative controls...
July 31, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28760351/therapeutic-strategies-for-locally-recurrent-and-metastatic-de-differentiated-liposarcoma-with-herpes-simplex-virus-thymidine-kinase-expressing-mesenchymal-stromal-cells
#5
Hyunjoo Lee, Eun Byeol Jo, Su Jin Kim, Heung Mo Yang, You Min Kim, Young Chul Sung, Jae Berm Park, Doopyo Hong, Hyojun Park, Yoon-La Choi, Sung Joo Kim
BACKGROUND AIMS: Major challenges in de-differentiated liposarcoma (DDLPS) therapy are the high rate of sequential recurrence (>80%) and metastasis (20-30%) following surgical removal. However, well-defined therapeutic strategies for this rare malignancy are lacking and are critically needed. METHODS: We investigated a new approach to DDLPS therapy with mesenchymal stromal cells expressing herpes simplex virus-thymidine kinase (MSC-TK). In an effort to evaluate this efficacy, in vitro cytotoxicity of MSC-TK against DDLPS cells was analyzed using an apoptosis assay...
July 28, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28756205/melanin-binding-study-of-clinical-drugs-with-cassette-dosing-and-rapid-equilibrium-dialysis-inserts
#6
Laura Pelkonen, Unni Tengvall-Unadike, Marika Ruponen, Heidi Kidron, Eva M Del Amo, Mika Reinisalo, Arto Urtti
Melanin pigment is a negatively charged polymer found in pigmented human tissues. In the eye, iris, ciliary body, choroid and retinal pigment epithelium (RPE) are heavily pigmented. Several drug molecules are known to bind to melanin, but larger sets of drugs have not been compared often in similar test conditions. In this study, we introduce a powerful tool for screening of melanin binding. The binding of a set of 34 compounds to isolated porcine RPE melanin was determined by cassette (n-in-one) dosing in rapid equilibrium dialysis inserts and the binding was quantitated with LC-MS/MS analytics...
July 27, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28748879/early-clinical-manifestations-and-laboratory-findings-before-and-after-treatment-of-cytomegalovirus-infection-in-kidney-transplant-patients
#7
Wasim Ahmed Siddiqui, Issa Al Salmi, Amitabh Jha, Abbas Pakkyara, Mohammad Yasir, Faissal A M Shaheen
Cytomegalovirus (CMV) is one of the most frequently encountered opportunistic viral pathogens in kidney transplant recipients. In this study, we retrospectively reviewed all living related and unrelated kidney transplant recipients on regular follow-up from January 2006 to June 2015, who were suspected to have CMV clinically and confirmed by DNA polymerase chain reaction (PCR). CMV PCR was detected in 102 kidney transplant recipients. The median time of detection after kidney transplant was 21 months, ranging from 15 days to 84 months...
July 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28748212/genetically-engineered-multilineage-differentiating-stress-enduring-cells-as-cellular-vehicles-against-malignant-gliomas
#8
Tomohiro Yamasaki, Shohei Wakao, Hiroshi Kawaji, Shinichiro Koizumi, Tetsuro Sameshima, Mari Dezawa, Hiroki Namba
Malignant glioma, the most common malignant brain tumor in adults, is difficult to treat due to its aggressive invasive nature. Enzyme/prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment with multilineage-differentiating stress-enduring (Muse) cells, which are endogenous non-tumorigenic pluripotent-like stem cells that are easily collectable from the bone marrow as SSEA-3(+) cells, as carriers of the HSVtk gene...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28746781/human-herpesvirus-6-encephalitis-following-chemotherapy-induction-for-acute-myelogenous-leukemia
#9
John W Frey, Joseph N Cherabie, Maha A Assi
We report a case of human herpesvirus-6 (HHV-6) encephalitis in a neutropenic patient who had undergone chemotherapy induction for acute myelogenous leukemia while on broad-spectrum antimicrobial therapy. The patient displayed symptoms of confusion, amnesia, and lethargy. Diagnosis was made via polymerase chain reaction analysis of cerebrospinal fluid. Electroencephalogram and magnetic resonance imaging of the brain were unremarkable. Following diagnosis, the patient was successfully treated with ganciclovir...
July 26, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28738449/pbpk-modeling-of-the-effect-of-reduced-kidney-function-on-the-pharmacokinetics-of-drugs-excreted-renally-by-organic-anion-transporters
#10
C-H Hsueh, V Hsu, P Zhao, L Zhang, K M Giacomini, S-M Huang
Altered pharmacokinetics (PK) in subjects with chronic kidney disease (CKD) may lead to dosing adjustment of certain drugs in subjects with CKD. It can be valuable to quantitatively predict PK in CKD for the management of drug dosing in these subjects. We developed physiologically based pharmacokinetic (PBPK) models of seven renally eliminated drugs: adefovir, avibactam, entecavir, famotidine, ganciclovir, oseltamivir carboxylate, and sitagliptin. These drugs are all substrates of renal organic anion transporters (OATs)...
July 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28734808/-congenital-cytomegalovirus-infection-manifesting-as-neonatal-respiratory-distress-in-an-hiv-exposed-uninfected-newborn
#11
A Pham, H El Mjati, N Nathan, F Kieffer, D Mitanchez
BACKGROUND: Cytomegalovirus (CMV) is one of the most common intrauterine infections, affecting approximately 1% of all live births. There are few reports on congenital CMV infections manifesting as isolated pneumonitis. CASE REPORT: We report a case of congenital CMV with neonatal respiratory distress affecting an HIV-exposed uninfected infant. This infant required noninvasive ventilation beginning within the first 15min of life. The initial chest X-ray showed diffuse bilateral ground-glass opacifications...
July 19, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28733760/intrauterine-therapy-of-cytomegalovirus-infection-with-valganciclovir-review-of-the-literature
#12
REVIEW
Vera Seidel, Cornelia Feiterna-Sperling, Jan-Peter Siedentopf, Jörg Hofmann, Wolfgang Henrich, Christoph Bührer, Katharina Weizsäcker
Congenital cytomegalovirus (CMV) infection is the leading cause for sensorineural hearing loss and mental retardation in children without genetic diseases worldwide. There is little evidence guiding therapeutic strategies during pregnancy when intrauterine fetal CMV infection is confirmed. We provide a systematic review of the use of ganciclovir (GCV) or VGCV during pregnancy discussing safety of its use for mother and fetus and describe two cases of intrauterine therapy of fetal CMV infection with valganciclovir (VGCV)...
July 21, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28731920/eye-movement-disorders-following-allogeneic-bone-marrow-transplantation-on-fk506-tacrolimus-and-ganciclovir
#13
Barbaros S Karagun, Tugana Akbas, Taner Arpaci, Bulent Antmen
FK506 (tacrolimus) is an immunosuppressive drug and more potent than cyclosporine. FK506 is widely used for immunosuppression in the prevention and treatment of graft-versus-host disease after allogeneic bone marrow transplantation and solid organ transplantation. Neurotoxicity is a recognized complication of FK506 therapy, but ptosis and weakness of eye abduction unilaterally has not been reported in association with FK506 administration to date. We discuss a 13-year-old male patient who developed ptosis and weakness of eye abduction unilaterally 90 days after transplantation with bone marrow from an unrelated donor, for acute lymphoblastic leukemia in this case report...
July 20, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28728316/use-of-novel-oral-anticoagulant-to-treat-pulmonary-thromboembolism-in-patient-with-ulcerative-colitis-superinfected-cytomegalovirus-colitis
#14
Seok Hwan Kim, Sunhee Jang, Yegyu Sung, Jun Kyu Park, Yunjung Park, Jintak Yun, Sang Bum Kang
Crohn's disease and ulcerative colitis are the two major types of inflammatory bowel disease, and affect mainly the gastrointestinal tract but also have extraintestinal sequelae, such as arterial and venous thromboembolism. Thromboembolic complications, particularly pulmonary thromboembolism, can be life threatening and require prompt management with anticoagulants. Conventional vitamin K antagonists have been used for the treatment of thromboembolic complications, but the development of novel oral anticoagulants has shifted the paradigm...
July 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28727740/genetically-engineered-suicide-gene-in-mesenchymal-stem-cells-using-a-tet-on-system-for-anaplastic-thyroid-cancer
#15
Senthilkumar Kalimuthu, Ji Min Oh, Prakash Gangadaran, Liya Zhu, Ho Won Lee, Yong Hyun Jeon, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Anaplastic thyroid cancer (ATC) is the most aggressive malignancy of the thyroid, during which undifferentiated tumors arise from the thyroid follicular epithelium. ATC has a very poor prognosis due to its aggressive behavior and poor response to conventional therapies. Gene-directed enzyme/prodrug therapy using genetically engineered mesenchymal stromal cells (MSC) is a promising therapeutic strategy. The doxycycline (DOX)-controlled Tet inducible system is the most widely utilized regulatory system and could be a useful tool for therapeutic gene-based therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#16
Pedro R Lowenstein, Maria G Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14-20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials...
July 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28711628/enteric-glia-regulate-gastrointestinal-motility-but-are-not-required-for-maintenance-of-the-epithelium-in-mice
#17
Meenakshi Rao, Daniella Rastelli, Lauren Dong, Sophia Chiu, Wanda Setlik, Michael D Gershon, Gabriel Corfas
BACKGROUND & AIMS: When the glial fibrillary acidic protein (GFAP) promoter is used to express cellular toxins that eliminate glia in mice, intestinal epithelial permeability and proliferation increase; this led to the concept that glia are required for maintenance of the gastrointestinal epithelium. Many enteric glia, however, particularly in the mucosa, do not express GFAP. In contrast, virtually all enteric glia express proteolipid protein 1 (PLP1). We investigated whether elimination of PLP1-expressing cells compromises epithelial maintenance or gastrointestinal motility...
July 12, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28704950/structure-activity-relationships-of-acyclic-selenopurine-nucleosides-as-antiviral-agents
#18
Pramod K Sahu, Tamima Umme, Jinha Yu, Gyudong Kim, Shuhao Qu, Siddhi D Naik, Lak Shin Jeong
A series of acyclic selenopurine nucleosides 3a-f and 4a-g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a) exhibited the most potent anti-herpes simplex virus (HSV)-1 (EC50 = 1.47 µM) and HSV-2 (EC50 = 6.34 µM) activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e-g exhibited significant anti-human cytomegalovirus (HCMV) activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d)...
July 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28699311/ganciclovir-resistant-cytomegalovirus-infection-in-abdominal-solid-organ-transplant-recipients-case-series-and-review-of-the-literature
#19
K E Rolling, M R Jorgenson, J L Fose, D A Mandelbrot, R R Redfield, J A Smith
Ganciclovir-resistant cytomegalovirus (GR-CMV) is emerging as a significant infection in the abdominal transplant population. GR-CMV is difficult to manage, and treatment options are limited. We report a descriptive case series of 15 patients who had documented GR-CMV at our center and review the literature on treatment of GR-CMV. The first case in this series was detected in 2012; the majority of cases occurred after January 1, 2014, with approximately 50% occurring in 2015. UL97 and UL54 viral genome mutations were present in 100% and 40% of CMV-infected patients, respectively...
July 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28663679/cytomegalovirus-infection-in-liver-transplant-recipients-current-approach-to-diagnosis-and-management
#20
REVIEW
Sanjay K Yadav, Sanjiv Saigal, Narendra S Choudhary, Sujit Saha, Navin Kumar, Arvinder S Soin
Cytomegalovirus (CMV) infection is the most common viral infection in liver transplant recipients, affecting post-transplant patients and graft survival. Recent advances in diagnosis and management of CMV have led to marked reduction in incidence, severity, and its associated morbidity and mortality. CMV DNA assay is the most commonly used laboratory parameter to diagnose and monitor CMV infection. Current evidence suggests that both pre-emptive and universal prophylaxis approaches are equally justified in liver transplant recipients...
June 2017: Journal of Clinical and Experimental Hepatology
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