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https://www.readbyqxmd.com/read/28821804/nos2-deficient-mice-with-hypoxic-necrotizing-lung-lesions-predict-outcomes-of-tuberculosis-chemotherapy-in-humans
#1
Martin Gengenbacher, Maria A Duque-Correa, Peggy Kaiser, Stefanie Schuerer, Doris Lazar, Ulrike Zedler, Stephen T Reece, Amit Nayyar, Stewart T Cole, Vadim Makarov, Clifton E Barry Iii, Véronique Dartois, Stefan H E Kaufmann
During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used in TB drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We found that Nos2 (-/-) mice incapable of NO-production in immune cells as microbial defence uniformly develop hypoxic necrotizing lung lesions, widely observed in human TB. To study the impact of hypoxic necrosis on the efficacy of antimycobacterials and drug candidates, we subjected Nos2 (-/-) mice with TB to monotherapy before or after establishment of human-like pathology...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821621/protein-kinase-g-confers-survival-advantage-to-mycobacterium-tuberculosis-during-latency-like-conditions
#2
Mehak Zahoor Khan, Ashima Bhaskar, Sandeep Upadhyay, Pooja Kumari, Raju S Rajmani, Preeti Jain, Amit Singh, Dhiraj Kumar, Neel Sarovar Bhavesh, Vinay Kumar Nandicoori
Protein Kinase G (PknG), a thioredoxin-fold containing eukaryotic like serine/threonine protein kinase (STPK), is a virulence factor in the Mycobacterium tuberculosis, required for inhibition of phago-lysosomal fusion. Here, we unravelled novel functional facets of PknG during latency like conditions. We find that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient limiting conditions suggesting its role in modulating cellular metabolism...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28816914/congenital-hypotonia-in-toddlerhood
#3
Naomi Steiner, Alcy Torres, Arathi Reddy, Marilyn Augustyn
David is a 22-month-old boy who is new to your practice. He recently moved from a rural area in the Midwest. His father is in the United States Air Force, and his mother works as a full-time homemaker. Their household includes 5 older siblings. The family moves every year because of the father's Air Force placement.David was born full-term in Virginia, with no reported pregnancy complications and no alcohol, tobacco, or drug exposure. He was delivered vaginally, with Apgar scores of 7 and 9, respectively and no respiratory issues...
August 9, 2017: Journal of Developmental and Behavioral Pediatrics: JDBP
https://www.readbyqxmd.com/read/28815569/glucose-dependent-leukocyte-activation-in-familial-hypercholesterolemia
#4
Natasja Koks, Marijke A de Vries, Erwin Birnie, Arash Alipour, Manuel Castro Cabezas
BACKGROUND: Leukocyte activation is an obligatory factor in the development of atherosclerosis. The postprandial situation has been associated to increased leukocyte activation in several disorders, such as type 2 diabetes mellitus and familial combined hyperlipidemia. Our study aim was to evaluate the effect of post-OGTT hyperglycemia on leukocyte activation in patients with familial hypercholesterolemia (FH). MATERIALS AND METHODS: Patients who met the diagnostic criteria for heterozygous FH and healthy volunteers were asked to undergo an oral glucose tolerance test...
August 16, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28808048/epigenetic-repression-of-line-1-elements-protects-drug-resistant-cells
#5
(no author information available yet)
H3K9me3-dependent heterochromatin formation maintains drug-tolerant persister (DTP) cell viability.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28789916/flecainide-reduces-ventricular-arrhythmias-in-patients-with-genotype-ryr2-positive-catecholaminergic-polymorphic-ventricular-tachycardia
#6
Fernando Wangüemert Pérez, Julio Salvador Hernández Afonso, María Del Val Groba Marco, Eduardo Caballero Dorta, Luis Álvarez Acosta, Oscar Campuzano Larrea, Guillermo Pérez, Josep Brugada Terradellas, Ramón Brugada Terradellas
INTRODUCTION AND OBJECTIVES: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by polymorphic or bidirectional ventricular arrhythmias (VA) triggered by physical or emotional stress in young people with a structurally normal heart. Beta-blockers are the cornerstone of treatment, while flecainide has recently been incorporated into the therapeutic arsenal. The aim of this study was to report our experience with this drug. METHODS: The cohort included 174 genotype-positive CPVT-patients from 7 families...
August 5, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28781121/repression-of-stress-induced-line-1-expression-protects-cancer-cell-subpopulations-from-lethal-drug-exposure
#7
Gulfem Dilek Guler, Charles Albert Tindell, Robert Pitti, Catherine Wilson, Katrina Nichols, Tommy KaiWai Cheung, Hyo-Jin Kim, Matthew Wongchenko, Yibing Yan, Benjamin Haley, Trinna Cuellar, Joshua Webster, Navneet Alag, Ganapati Hegde, Erica Jackson, Tracy Leah Nance, Paul Garrett Giresi, Kuan-Bei Chen, Jinfeng Liu, Suchit Jhunjhunwala, Jeff Settleman, Jean-Philippe Stephan, David Arnott, Marie Classon
Maintenance of phenotypic heterogeneity within cell populations is an evolutionarily conserved mechanism that underlies population survival upon stressful exposures. We show that the genomes of a cancer cell subpopulation that survives treatment with otherwise lethal drugs, the drug-tolerant persisters (DTPs), exhibit a repressed chromatin state characterized by increased methylation of histone H3 lysines 9 and 27 (H3K9 and H3K27). We also show that survival of DTPs is, in part, maintained by regulators of H3K9me3-mediated heterochromatin formation and that the observed increase in H3K9me3 in DTPs is most prominent over long interspersed repeat element 1 (LINE-1)...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28762672/safety-efficacy-and-persistence-of-long-term-mirabegron-treatment-for-overactive-bladder-in-the-daily-clinical-setting-interim-1-year-report-from-a-japanese-post-marketing-surveillance-study
#8
Daisuke Kato, Hiromi Tabuchi, Satoshi Uno
OBJECTIVES: To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). METHODS: Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations...
August 1, 2017: Lower Urinary Tract Symptoms
https://www.readbyqxmd.com/read/28759492/chronic-hiccups-an-underestimated-problem
#9
Eva K Kohse, Markus W Hollmann, Hubert J Bardenheuer, Jens Kessler
Persistent singultus, hiccupping that lasts for longer than 48 hours, can have a tremendous impact on a patient's quality of life. Although involved neurologic structures have been identified, the function of hiccups remains unclear-they have been controversially interpreted as a primitive reflex preventing extent swallowing of amniotic fluid in utero, an archaic gill ventilation pattern, or a fetus' preparation for independent breathing. Persistent singultus often presents as a symptom for various diseases, most commonly illnesses of the central nervous system or gastrointestinal tract; they can also be evoked by a variety of pharmacological agents...
July 26, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28757235/adult-onset-still-s-disease-the-evidence-that-anti-interleukin-1-treatment-is-effective-and-well-tolerated-a-comprehensive-literature-review
#10
REVIEW
Guido Junge, June Mason, Eugen Feist
The literature contains many reports of the use of commercially available anti-IL-1 agents (anakinra/Kineret(®), canakinumab/Ilaris(®), or rilonacept/Arcalyst(®)) in treatment-resistant adult-onset Still's disease (AOSD). These have been widely summarized in many review articles, but a full account of all reports with each of the agents used is not available. This literature review includes all reports of treatment outcomes in patients treated for AOSD with any commercially available anti-IL-1 agent (excluding cases of unconfirmed or atypical AOSD or treatments only for rare AOSD complications)...
June 23, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28756902/bevacizumab-for-advanced-cervical-cancer-final-overall-survival-and-adverse-event-analysis-of-a-randomised-controlled-open-label-phase-3-trial-gynecologic-oncology-group-240
#11
Krishnansu S Tewari, Michael W Sill, Richard T Penson, Helen Huang, Lois M Ramondetta, Lisa M Landrum, Ana Oaknin, Thomas J Reid, Mario M Leitao, Helen E Michael, Philip J DiSaia, Larry J Copeland, William T Creasman, Frederick B Stehman, Mark F Brady, Robert A Burger, J Tate Thigpen, Michael J Birrer, Steven E Waggoner, David H Moore, Katherine Y Look, Wui-Jin Koh, Bradley J Monk
BACKGROUND: On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified final analysis of the primary objectives, OS and adverse events. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients with metastatic, persistent, or recurrent cervical carcinoma from 81 centres in the USA, Canada, and Spain...
July 27, 2017: Lancet
https://www.readbyqxmd.com/read/28753272/colony-lysate-arrays-for-proteomic-profiling-of-drug-tolerant-persisters-of-cancer-cell
#12
Kohei Kume, Satoshi S Nishizuka
Functional heterogeneity of cancer cells is one of the key properties to understanding relapse after drug treatment. Hence, clarification is needed with regard to which types of subgroups of cancer cells dominantly contribute to the initiation of relapse. Recently, we established the colony lysate array (CoLA), which is a method that allows comparison of individual colonies at the protein level to assess the initiation of anticancer drug-tolerant persisters (DTPs) based on the reverse-phase protein array (RPPA) system...
August 11, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28750828/efficacy-and-safety-of-alirocumab-versus-ezetimibe-over-2-years-from-odyssey-combo-ii
#13
Mahfouz El Shahawy, Christopher P Cannon, Dirk J Blom, James M McKenney, Bertrand Cariou, Guillaume Lecorps, Robert Pordy, Umesh Chaudhari, Helen M Colhoun
The proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to substantially reduce low-density lipoprotein cholesterol (LDL-C). Demonstrating whether efficacy and safety are maintained over a long duration of exposure is vital for clinical decision-making. The COMBO II trial compared the efficacy and safety of alirocumab versus ezetimibe over 2 years. A prespecified first analysis was reported at 52 weeks. Here we report the final end-of-study data (on-treatment) and evaluate post hoc the safety profile with longer versus shorter duration of alirocumab exposure...
June 28, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28748731/long-term-management-of-distinct-facial-flushing-and-persistent-erythema-of-rosacea-by-treatment-with-carvedilol
#14
Katharina Pietschke, Martin Schaller
BACKGROUND: The treatment of persistent erythema and flushing episodes in patients with rosacea remains a clinical challenge. A possible therapeutic option could be given be the use of antihypertensive drugs. OBJECTIVES: We therefore evaluated the effect of the non-selective β-blocker carvedilol in five caucasian patients. METHODS: In a monocentric, retrospective case study the patients were treated with carvedilol titrated up to 12.5 mg twice a day over at least six months...
July 27, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28748194/recurrent-metatarsal-fractures-in-postmenopausal-woman-with-low-serum-alkaline-phosphatase-a-rare-diagnosis-not-to-miss
#15
Umair Iqbal, Hafsa Anwar, Ahmad Chaudhary, Madiha Alvi, Amy Freeth
Hypophosphatasia (HPP) is a rare inborn error of metabolism due to a loss-of-function mutation in the gene for tissue nonspecific isoenzyme of alkaline phosphatase (ALP) that results in low levels of ALP. The clinical presentation of HPP is variable and in adults can easily be misdiagnosed as other forms of osteomalacia. We present a case of a 53-year-old Caucasian female who was evaluated for recurrent metatarsal fractures. She reported her first metatarsal fracture at age 21, and since then had at least 8 more metatarsal fractures over her lifetime, most without injury other than weight bearing...
July 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28741970/efficacy-and-safety-of-once-weekly-semaglutide-for-the-treatment-of-type-2-diabetes
#16
Xueying Tan, Xiaojing Cao, Minzhi Zhou, Ping Zou, Jingbo Hu
Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of Diabetes promote a patient-centered approach that takes into account a comprehensive consideration of pharmacological properties of drugs, including glucose-lowering action, effects on body weight, correction on multiple pathophysiologic defects, tolerability, and long-term safety...
July 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28735367/short-term-and-long-term-effects-of-diazepam-on-the-memory-for-discrimination-and-generalization-of-scopolamine
#17
C Casasola-Castro, L Weissmann-Sánchez, E Calixto-González, A Aguayo-Del Castillo, D N Velázquez-Martínez
Benzodiazepines are among the most widely prescribed and misused psychopharmaceutical drugs. Although they are well-tolerated, they are also capable of producing amnestic effects similar to those observed after pharmacological or organic cholinergic dysfunction. To date, the effect of benzodiazepine diazepam on the memory for discrimination of anticholinergic drugs has not been reported. The aim of the present study was to analyze the immediate and long-term effects of diazepam on a drug discrimination task with scopolamine...
July 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28729164/antenatal-antipsychotic-exposure-induces-multigenerational-and-gender-specific-programming-of-adiposity-and-glucose-tolerance-in-adult-mouse-offspring
#18
E Courty, P Gobalakichenane, M Garcia, A Muscat, C Kazakian, T Ledent, M Moldes, B Blondeau, D Mitanchez, M Buyse, B Fève
Second-generation antipsychotics (SGAs) are well known for their metabolic side effects in humans, including obesity and diabetes. These compounds are maintained during pregnancy to prevent the relapse of psychoses, but they readily diffuse across the placenta to the fetus, as documented with the widely-prescribed drug olanzapine (OLZ). However, observational studies have provided conflicting results on the potential impact of SGAs on fetal growth and body weight, and their effects on metabolic regulation in the offspring...
July 17, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28728751/a-phase-ii-evaluation-of-brivanib-in-the-treatment-of-persistent-or-recurrent-carcinoma-of-the-cervix-an-nrg-oncology-gynecologic-oncology-group-study
#19
John K Chan, Wei Deng, Robert V Higgins, Krishnansu S Tewari, Albert J Bonebrake, Michael Hicks, Stephanie Gaillard, Pedro T Ramirez, Weldon Chafe, Bradley J Monk, Carol Aghajanian
BACKGROUND: Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. METHODS: Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity...
July 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#20
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
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