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https://www.readbyqxmd.com/read/29163503/efferocytosis-and-outside-in-signaling-by-cardiac-phagocytes-links-to-repair-cellular-programming-and-intercellular-crosstalk-in-heart
#1
REVIEW
Matthew DeBerge, Shuang Zhang, Kristofor Glinton, Luba Grigoryeva, Islam Hussein, Esther Vorovich, Karen Ho, Xunrong Luo, Edward B Thorp
Phagocytic sensing and engulfment of dying cells and extracellular bodies initiate an intracellular signaling cascade within the phagocyte that can polarize cellular function and promote communication with neighboring non-phagocytes. Accumulating evidence links phagocytic signaling in the heart to cardiac development, adult myocardial homeostasis, and the resolution of cardiac inflammation of infectious, ischemic, and aging-associated etiology. Phagocytic clearance in the heart may be carried out by professional phagocytes, such as macrophages, and non-professional cells, including myofibrolasts and potentially epithelial cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162023/pentobarbital-removal-during-continuous-venovenous-hemofiltration-case-report-and-review-of-the-literature
#2
David M Hensler, Deepika P McConnell, Kimberly E Levasseur-Franklin, Kasey M Greathouse
BACKGROUND: Renal replacement therapy may enhance the elimination of barbiturates. Pentobarbital clearance during continuous venovenous hemofiltration (CVVH) has not been described previously. We report a patient case involving the measurement of serial pentobarbital levels during CVVH and review relevant literature characterizing extracorporeal pentobarbital elimination. METHODS: The following is a retrospective report of a previously healthy 26-year-old woman who sustained a severe traumatic brain injury (TBI) and required administration of pentobarbital on hospital day 0 for intracranial pressure (ICP) control...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29156373/mitochondria-targeted-ubiquinone-mitoq-enhances-acetaldehyde-clearance-by-reversing-alcohol-induced-posttranslational-modification-of-aldehyde-dehydrogenase-2-a-molecular-mechanism-of-protection-against-alcoholic-liver-disease
#3
Liuyi Hao, Qian Sun, Wei Zhong, Wenliang Zhang, Xinguo Sun, Zhanxiang Zhou
Alcohol metabolism in the liver generates highly toxic acetaldehyde. Breakdown of acetaldehyde by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria consumes NAD(+) and generates reactive oxygen/nitrogen species, which represents a fundamental mechanism in the pathogenesis of alcoholic liver disease (ALD). A mitochondria-targeted lipophilic ubiquinone (MitoQ) has been shown to confer greater protection against oxidative damage in the mitochondria compared to untargeted antioxidants. The present study aimed to investigate if MitoQ could preserve mitochondrial ALDH2 activity and speed up acetaldehyde clearance, thereby protects against ALD...
November 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/29149600/repair-of-uv-induced-dna-damage-independent-of-nucleotide-excision-repair-is-masked-by-mutyh
#4
Abdelghani Mazouzi, Federica Battistini, Sarah C Moser, Joana Ferreira da Silva, Marc Wiedner, Michel Owusu, Charles-Hugues Lardeau, Anna Ringler, Beatrix Weil, Jürgen Neesen, Modesto Orozco, Stefan Kubicek, Joanna I Loizou
DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defects. There are currently no curative therapies available. Here we performed a high-throughput chemical screen for agents that could alleviate the cellular sensitivity of NER-deficient cells to UV-induced DNA damage...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149205/kir-content-genotypes-associate-with-carriage-of-hepatitis-b-surface-antigen-e-antigen-and-hbv-viral-load-in-gambians
#5
Louis-Marie Yindom, Maimuna Mendy, Christopher Bodimeade, Caroline Chambion, Peter Aka, Hilton C Whittle, Sarah L Rowland-Jones, Robert Walton
BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation...
2017: PloS One
https://www.readbyqxmd.com/read/29146903/wiskott-aldrich-syndrome-protein-regulates-autophagy-and-inflammasome-activity-in-innate-immune-cells
#6
Pamela P Lee, Damián Lobato-Márquez, Nayani Pramanik, Andrea Sirianni, Vanessa Daza-Cajigal, Elizabeth Rivers, Alessia Cavazza, Gerben Bouma, Dale Moulding, Kjell Hultenby, Lisa S Westerberg, Michael Hollinshead, Yu-Lung Lau, Siobhan O Burns, Serge Mostowy, Mona Bajaj-Elliott, Adrian J Thrasher
Dysregulation of autophagy and inflammasome activity contributes to the development of auto-inflammatory diseases. Emerging evidence highlights the importance of the actin cytoskeleton in modulating inflammatory responses. Here we show that deficiency of Wiskott-Aldrich syndrome protein (WASp), which signals to the actin cytoskeleton, modulates autophagy and inflammasome function. In a model of sterile inflammation utilizing TLR4 ligation followed by ATP or nigericin treatment, inflammasome activation is enhanced in monocytes from WAS patients and in WAS-knockout mouse dendritic cells...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29135922/targeting-immune-cell-checkpoints-during-sepsis
#7
REVIEW
Naeem K Patil, Yin Guo, Liming Luan, Edward R Sherwood
Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell membrane protein-3 (TIM-3), Lymphocyte activation-gene-3 (LAG-3) and 2B4, are upregulated during the course of sepsis...
November 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29135030/hepatitis-c-virus-clearance-in-older-adults
#8
Antonio Massimo Ippolito, Angelo Iacobellis, Michele Milella, Fabio Conti, Vincenzo Messina, Maria Rosa Valvano, Grazia Anna Niro, Filomena Morisco, Michele Barone, Antonio Patrizio Termite, Giuseppina Brancaccio, Angelo Andriulli
OBJECTIVES: To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy. PARTICIPANTS: Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis). MEASUREMENTS: We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs)...
November 14, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/29134426/pharmacokinetics-and-safety-of-amenamevir-in-healthy-subjects-analysis-of-four-randomized-phase-1-studies
#9
Tomohiro Kusawake, James J Keirns, Donna Kowalski, Martin den Adel, Dorien Groenendaal-van de Meent, Akitsugu Takada, Yoshiaki Ohtsu, Masataka Katashima
INTRODUCTION: Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella-zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants. METHODS: Four randomized phase 1 studies investigated the safety and pharmacokinetics of single and multiple doses of amenamevir, including the assessment of age group effect (nonelderly vs elderly), food effect, and the relative bioavailability of two formulations...
November 13, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29123950/immune-evasion-mechanisms-and-immune-checkpoint-inhibition-in-advanced-merkel-cell-carcinoma
#10
REVIEW
Dirk Schadendorf, Paul Nghiem, Shailender Bhatia, Axel Hauschild, Philippe Saiag, Lisa Mahnke, Subramanian Hariharan, Howard L Kaufman
Merkel cell carcinoma (MCC) is a rare skin cancer caused by Merkel cell polyomavirus (MCPyV) infection and/or ultraviolet radiation-induced somatic mutations. The presence of tumor-infiltrating lymphocytes is evidence that an active immune response to MCPyV and tumor-associated neoantigens occurs in some patients. However, inhibitory immune molecules, including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), within the MCC tumor microenvironment aid in tumor evasion of T-cell-mediated clearance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123419/encephalitis-treatment-a-case-report-with-long-term-follow-up-of-ebv-pcr-in-cerebrospinal-fluid
#11
Fnu Zarlasht, Mashal Salehi, Mohammad Abu-Hishmeh, Muzammil Khan
Background: Epstein-Barr virus (EBV) has been found to cause infectious mononucleosis multiple times, but has been associated rarely with EBV encephalitis. Also, whenever it is diagnosed, it is always treated symptomatically. Case report: A case of confirmed EBV encephalitis is presented, which was treated with antiviral therapy resulting in complete clearance of the virus in cerebrospinal fluid and minimal neurologic symptoms after hospital discharge. Conclusion: The Infectious Diseases Society of America guidelines state that intravenous acyclovir is not recommended for EBV-related encephalitis...
2017: International Journal of General Medicine
https://www.readbyqxmd.com/read/29121969/microglial-dynamics-after-axotomy-induced-retinal-ganglion-cell-death
#12
Francisco M Nadal-Nicolás, Manuel Jiménez-López, Manuel Salinas-Navarro, Paloma Sobrado-Calvo, Manuel Vidal-Sanz, Marta Agudo-Barriuso
BACKGROUND: Microglial cells (MCs) are the sentries of the central nervous system. In health, they are known as surveying MCs because they examine the tissue to maintain the homeostasis. In disease, they activate and, among other functions, become phagocytic to clean the cellular debris. In this work, we have studied the behavior of rat retinal MCs in two models of unilateral complete intraorbital optic nerve axotomy which elicit a different time course of retinal ganglion cell (RGC) loss...
November 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29121965/chronic-cerebral-hypoperfusion-induces-post-stroke-dementia-following-acute-ischemic-stroke-in-rats
#13
Dong Bin Back, Kyoung Ja Kwon, Dong-Hee Choi, Chan Young Shin, Jongmin Lee, Seol-Heui Han, Hahn Young Kim
BACKGROUND: Post-stroke dementia (PSD) is one of the major consequences after stroke. Chronic cerebral hypoperfusion (CCH) can induce vascular cognitive impairment and potentiate amyloid pathology. We investigated how CCH contributes to the development of PSD after stroke in the context of neuroinflammation and amyloid pathology. METHODS: We designed a unique animal model for PSD. We performed middle cerebral artery occlusion (MCAO) surgery in rats mimicking acute territorial infarct, which was followed by bilateral common carotid artery occlusion (BCCAo) surgery mimicking CCH...
November 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#14
REVIEW
Uriel Trahtemberg, Dror Mevorach
Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29114005/residual-kidney-function-and-peritoneal-dialysis-associated-peritonitis-treatment-outcomes
#15
Rachel Whitty, Joanne M Bargman, Alex Kiss, Linda Dresser, Philip Lui
BACKGROUND AND OBJECTIVES: Residual kidney function contributes to the clearance of antibiotics excreted by the kidneys, lowering the antibiotic concentration, which may adversely affect the treatment of peritoneal dialysis-associated peritonitis. The objective of our study was to examine the relationship between residual kidneyfunction and peritonitis treatment outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study included 181 participants who experienced 339 episodes of Gram-positive, Gram-negative, and culture-negative peritoneal dialysis-associated peritonitis at a single centerfrom 2003 to 2010...
November 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29101355/particles-of-different-sizes-and-shapes-induce-neutrophil-necroptosis-followed-by-the-release-of-neutrophil-extracellular-trap-like-chromatin
#16
Jyaysi Desai, Orestes Foresto-Neto, Mohsen Honarpisheh, Stefanie Steiger, Daigo Nakazawa, Bastian Popper, Eva Miriam Buhl, Peter Boor, Shrikant R Mulay, Hans-Joachim Anders
The human body is exposed to a wide range of particles of industrial, environmental or internal origin such as asbestos, alum, silica or crystals of urate, calcium phosphate, calcium oxalate, cystine or cholesterol. Phagocytic clearance of such particles involves neutrophils and macrophages. Here we report that neutrophils encountering such particles of diverse sizes and shapes undergo necrotic cell death, a process associated with the formation of neutrophil extracellular trap (NET)-like extracellular DNA...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29097427/nlrp3-inflammasome-activation-in-aged-macrophages-is-diminished-during-streptococcus-pneumoniae-infection
#17
Soo Jung Cho, Kristen T Rooney, Augustine M K Choi, Heather W Stout-Delgado
Pneumococcal infections are the 8th leading cause of death in the United States and it is estimated that older patients (>65 years of age) account for the most serious cases. The goal of our current study is to understand the impact of biological aging on innate immune responses to Streptococcus pneumoniae, a causative agent of bacterial pneumonia. Using in vitro and in vivo aged murine models, our findings demonstrate that age-enhanced unfolded protein responses (UPR) contribute to diminished inflammasome assembly and activation during S...
November 2, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29093083/dynamics-of-sendai-virus-spread-clearance-and-immunotherapeutic-efficacy-after-hematopoietic-cell-transplant-imaged-non-invasively-in-mice
#18
Heba H Mostafa, Peter Vogel, Ashok Srinivasan, Charles J Russell
There are no approved vaccines or virus-specific treatments for human parainfluenza viruses (PIVs), which have recently been reclassified into species human respirovirus 1 and 3 and human rubulavirus 2 and 4 These viruses cause morbidity and mortality in immunocompromised patients including those undergoing hematopoietic cell transplant (HCT). No small-animal models exist for non-invasive imaging of respiratory viral infection in the HCT host despite the utility such a system would offer to monitor prolonged infection, its clearance, and treatment options...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29092034/reporting-of-ethics-in-peer-reviewed-verbal-autopsy-studies-a-systematic-review
#19
Rohina Joshi, Neha Faruqui, Shilpa R Nagarajan, Rasika Rampatige, Alex Martiniuk, Hebe Gouda
Introduction: Verbal autopsy (VA) is a method that determines the cause of death by interviewing a relative of the deceased about the events occurring before the death, in regions where medical certification of cause of death is incomplete. This paper aims to review the ethical standards reported in peer-reviewed VA studies. Methods: A systematic review of Medline and Ovid was conducted by two independent researchers. Data were extracted and analysed for articles based on three key areas: Institutional Review Board (IRB) clearance and consenting process; data collection and management procedures, including: time between death and interview; training and education of interviewer, confidentiality of data and data security; and declarations of funding and conflict of interest...
October 30, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29081626/ceftriaxone-for-the-treatment-of-methicillin-susceptible-staphylococcus-aureus-bacteremia-a-case-series
#20
Rachel Amanda Lowe, Katie Elizabeth Barber, Jamie Leigh Wagner, Allison Miriam Bell-Harlan, Kayla Renay Stover
Methicillin-susceptible Staphylococcus aureus (MSSA) causes 45% of S. aureus bloodstream infections (BSI) and is the most important cause of BSI-associated death. The standard of care therapy is an anti-staphylococcal penicillin or cefazolin, but dosing frequencies for these agents are often infeasible; multiple daily doses tie up infusion lines and are impractical for outpatient antibiotic infusion. Ceftriaxone represents a promising alternative, with once daily dosing and a short infusion time. Currently, treatment with ceftriaxone for invasive MSSA infections is infrequent, with minimal data supporting the clinical utility of ceftriaxone for MSSA BSI...
July 2017: Journal of Pharmacology & Pharmacotherapeutics
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