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https://www.readbyqxmd.com/read/28922810/a-shock-and-awe-thioridazine-and-moxifloxacin-combination-based-regimen-for-pulmonary-mycobacterium-avium-intracellulare-complex-disease
#1
Shashikant Srivastava, Devyani Deshpande, Carleton M Sherman, Tawanda Gumbo
Objectives: To develop a thioridazine/moxifloxacin-based combination regimen for treatment of pulmonary infection due to Mycobacterium avium-intracellulare complex (MAC) that kills bacteria faster than the standard treatment regimen. Methods: Monocytes were infected with MAC and inoculated into the hollow-fibre system model for pulmonary MAC disease (HFS-MAC). We co-administered ethambutol plus azithromycin daily for 28 days, to achieve the same human concentration-time profiles that result from standard doses, in three HFS-MAC systems...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922806/linezolid-as-treatment-for-pulmonary-mycobacterium-avium-disease
#2
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Tawanda Gumbo
Objectives: To identify the pharmacokinetic/pharmacodynamic parameters and exposures of linezolid in the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: Human-derived monocytes infected with MAC were inoculated into hollow-fibre systems for dose-effect and dose-scheduling studies. We mimicked linezolid concentration-time profiles achieved in adult human lungs treated for 28 days. Sampling to confirm that the intended linezolid pharmacokinetics had been achieved, and for enumeration of MAC colony-forming units, was performed based on repetitive sampling from each system over the 28 days...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922805/failure-of-the-azithromycin-and-ethambutol-combination-regimen-in-the-hollow-fibre-system-model-of-pulmonary-mycobacterium-avium-infection-is-due-to-acquired-resistance
#3
Shashikant Srivastava, Devyani Deshpande, Tawanda Gumbo
Objectives: To investigate the performance of the two backbone drugs in the standard combination therapy regimen in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) infection. Methods: Six HFS were inoculated with human-derived monocytes infected with MAC, and treated with 15 mg/kg of ethambutol and 500 mg of azithromycin daily for 28 days to recapitulate the concentration-time profiles seen in the lungs of humans treated with these drugs and doses...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922589/higher-baseline-proinflammatory-cytokines-mark-poor-antidepressant-response-in-bipolar-disorder
#4
Francesco Benedetti, Sara Poletti, Thomas A Hoogenboezem, Clara Locatelli, Harm de Wit, Annemarie J M Wijkhuijs, Cristina Colombo, Hemmo A Drexhage
BACKGROUND: The clinical relevance of raised levels of circulating cytokines in bipolar disorder is still unclear. Cytokines influence neurotransmitters, neuroplasticity, and white matter integrity. An inconsistent literature suggests that higher cytokine levels could hamper antidepressant response. Total sleep deprivation (TSD) and light therapy (LT) prompt a rapid antidepressant response and can provide a model treatment to study predictors of response. METHODS: We studied at baseline 15 immune-regulating compounds in 37 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder (DSM-5 criteria) and in 24 controls...
September 12, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28922584/characterization-and-pro-inflammatory-responses-of-spore-and-hyphae-samples-from-various-mold-species
#5
E Øya, Akj Afanou, N Malla, S Uhlig, E Rolen, I Skaar, A Straumfors, J O Winberg, B E Bang, P E Schwarze, W Eduard, J A Holme
Mold particles from Aspergillus fumigatus, Penicillium chrysogenum, Aspergillus versicolor and Stachybotrys chartarum have been linked to respiratory-related diseases. Here we characterized X-ray-inactivated spores and hyphae fragments from these species by number of particles, morphology, and mycotoxin, β-glucan and protease content/activity. The pro-inflammatory properties of mold particles were examined in human bronchial epithelial cells (BEAS-2B) and THP-1 monocytes and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1...
September 18, 2017: Indoor Air
https://www.readbyqxmd.com/read/28922563/role-of-il-18-in-atopic-asthma-is-determined-by-balance-of-il-18-il-18bp-il-18r
#6
Huiyun Zhang, Junling Wang, Ling Wang, Hua Xie, Liping Chen, Shaoheng He
It is recognized that IL-18 is related to development of asthma, but role of IL-18 in asthma remains controversial and confusing. This is largely due to lack of information on expression of IL-18 binding protein (BP) and IL-18 receptor (R) in asthma. In this study, we found that plasma levels of IL-18 and IL-18BP were elevated in asthma. The ratio between plasma concentrations of IL-18 and IL-18BP was 1:12.8 in asthma patients. We demonstrated that 13-fold more monocytes, 17.5-fold more neutrophils and 4.1-fold more B cells express IL-18BP than IL-18 in asthmatic blood, suggesting that there is excessive amount of IL-18BP to abolish actions of IL-18 in asthma...
September 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28922415/rewiring-monocyte-glucose-metabolism-via-c-type-lectin-signaling-protects-against-disseminated-candidiasis
#7
Jorge Domínguez-Andrés, Rob J W Arts, Rob Ter Horst, Mark S Gresnigt, Sanne P Smeekens, Jacqueline M Ratter, Ekta Lachmandas, Lily Boutens, Frank L van de Veerdonk, Leo A B Joosten, Richard A Notebaart, Carlos Ardavín, Mihai G Netea
Monocytes are innate immune cells that play a pivotal role in antifungal immunity, but little is known regarding the cellular metabolic events that regulate their function during infection. Using complementary transcriptomic and immunological studies in human primary monocytes, we show that activation of monocytes by Candida albicans yeast and hyphae was accompanied by metabolic rewiring induced through C-type lectin-signaling pathways. We describe that the innate immune responses against Candida yeast are energy-demanding processes that lead to the mobilization of intracellular metabolite pools and require induction of glucose metabolism, oxidative phosphorylation and glutaminolysis, while responses to hyphae primarily rely on glycolysis...
September 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28922396/biochemical-and-immunological-characterization-of-a-novel-monoclonal-antibody-against-mouse-leukotriene-b4-receptor-1
#8
Fumiyuki Sasaki, Tomoaki Koga, Kazuko Saeki, Toshiaki Okuno, Saiko Kazuno, Tsutomu Fujimura, Yasuyuki Ohkawa, Takehiko Yokomizo
Leukotriene B4 (LTB4) receptor 1 (BLT1) is a G protein-coupled receptor expressed in various leukocyte subsets; however, the precise expression of mouse BLT1 (mBLT1) has not been reported because a mBLT1 monoclonal antibody (mAb) has not been available. In this study, we present the successful establishment of a hybridoma cell line (clone 7A8) that produces a high-affinity mAb for mBLT1 by direct immunization of BLT1-deficient mice with mBLT1-overexpressing cells. The specificity of clone 7A8 was confirmed using mBLT1-overexpressing cells and mouse peripheral blood leukocytes that endogenously express BLT1...
2017: PloS One
https://www.readbyqxmd.com/read/28920098/the-il-1ri-co-receptor-tilrr-frem1%C3%A2-isoform-2-controls-aberrant-inflammatory-responses-and-development-of-vascular-disease
#9
Sarah A Smith, Andriy O Samokhin, Mabruka Alfadi, Emer C Murphy, David Rhodes, W Mike L Holcombe, Endre Kiss-Toth, Robert F Storey, Siu-Pok Yee, Sheila E Francis, Eva E Qwarnstrom
Expression of the interleukin-1 receptor type I (IL-1RI) co-receptor Toll-like and interleukin-1 receptor regulator (TILRR) is significantly increased in blood monocytes following myocardial infarction and in the atherosclerotic plaque, whereas levels in healthy tissue are low. TILRR association with IL-1RI at these sites causes aberrant activation of inflammatory genes, which underlie progression of cardiovascular disease. The authors show that genetic deletion of TILRR or antibody blocking of TILRR function reduces development of atherosclerotic plaques...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28920004/targeting-myeloid-derived-suppressor-cells-with-all-trans-retinoic-acid-is-highly-time-dependent-in-therapeutic-tumor-vaccination
#10
Annkristin Heine, Chrystel Flores, Heidrun Gevensleben, Linda Diehl, Mathias Heikenwalder, Marc Ringelhan, Klaus-Peter Janssen, Ulrich Nitsche, Natalio Garbi, Peter Brossart, Percy A Knolle, Christian Kurts, Bastian Höchst
Tumor immune escape is a critical problem which frequently accounts for the failure of therapeutic tumor vaccines. Among the most potent suppressors of tumor immunity are myeloid derived suppressor cells (MDSCs). MDSCs can be targeted by all-trans-retinoic-acid (atRA), which reduced their numbers and increased response rates in several vaccination studies. However, not much is known about the optimal administration interval between atRA and the vaccine as well as about its mode of action. Here we demonstrate in 2 different murine tumor models that mice unresponsive to a therapeutic vaccine harbored higher MDSC numbers than did responders...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919985/human-tumor-derived-exosomes-tex-regulate-treg-functions-via-cell-surface-signaling-rather-than-uptake-mechanisms
#11
Laurent Muller, Patricia Simms, Chang-Sook Hong, Michael I Nishimura, Edwin K Jackson, Simon C Watkins, Theresa L Whiteside
Tumor-derived exosomes (TEX) are ubiquitously present in the tumor microenvironment and plasma of cancer patients. TEX carry a cargo of multiple stimulatory and inhibitory molecules and deliver them to recipient cells, serving as a communication network for the tumor. The mechanisms TEX use for delivering messages to recipient cells were evaluated using PKH26-labeled TEX produced by cultured human tumor cells, exosomes produced by dendritic cells-derived exosomes (DEX), or exosomes isolated from plasma of cancer patients (EXO)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919897/altered-immune-activation-and-il-23-signaling-in-response-to-candida-albicans-in-autoimmune-polyendocrine-syndrome-type-1
#12
Øyvind Bruserud, Eirik Bratland, Alexander Hellesen, Nicolas Delaleu, Håkon Reikvam, Bergithe E Oftedal, Anette S B Wolff
OBJECTIVE: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare, childhood onset disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis (CMC) is one of the three major disease components and is, to date, mainly explained by the presence of neutralizing auto-antibodies against cytokines [interleukin (IL)-17A, IL-17F, and IL-22] from T helper 17 cells, which are critical for the protection against fungal infections. However, patients without current auto-antibodies also present CMC and we, therefore, hypothesized that other immune mechanisms contribute to CMC in APS-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28919896/vhh-based-bispecific-antibodies-targeting-cytokine-production
#13
Maxim A Nosenko, Kamar-Sulu N Atretkhany, Vladislav V Mokhonov, Grigory A Efimov, Andrey A Kruglov, Sergei V Tillib, Marina S Drutskaya, Sergei A Nedospasov
Proinflammatory cytokines, such as TNF, IL-6, and IL-1, play pathogenic roles in multiple diseases and are attractive targets for biologic drugs. Because proinflammatory cytokines possess non-redundant protective and immunoregulatory functions, their systemic neutralization carries the potential for unwanted side effects. Therefore, next-generation anti-cytokine therapies would seek to selectively neutralize pathogenic cytokine signaling, leaving normal function intact. Fortunately, the biology of proinflammatory cytokines provides several such opportunities...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28919108/the-renin-angiotensin-system-regulates-neurodegeneration-in-a-mouse-model-of-optic-neuritis
#14
Xiaoli Guo, Kazuhiko Namekata, Atsuko Kimura, Chikako Harada, Takayuki Harada
The major role of the renin-angiotensin system (RAS), including that of angiotensin II (Ang II), the principal effector molecule, in the cardiovascular system is well known. Increasing evidence suggests that the RAS also plays a role in the development of autoimmune diseases. Optic neuritis (ie, inflammation of the optic nerve, with retinal ganglion cell [RGC] loss) is strongly associated with multiple sclerosis (MS). Herein, we investigated the effects of candesartan, an Ang II receptor antagonist, on optic neuritis in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
September 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28919104/elevated-urinary-monocyte-chemoattractant-protein-1-levels-in-children-with-henoch-schonlein-purpura-nephritis
#15
Jiapei Wang, Qianqian Ying, Shiling Zhong, Yuanling Chen, Yazhen Di, Xiahua Dai, Jika Zheng, Mengjiao Shen
BACKGROUND: Chemokine monocyte chemoattractant protein-1 (MCP-1) has been proved as a potential urinary biomarker in nephropathies. The aim of this study was to investigate the urinary monocyte chemoattractant protein-1 (MCP-1) levels and clinical significance in Henoch-Schonlein purpura (HSP) children with and without nephritis and determine the association of MCP-1 with proteinuria. METHODS: A total of 261 HSP children-with or without nephritis-and 84 healthy control children were enrolled in this study...
August 26, 2017: Pediatrics and Neonatology
https://www.readbyqxmd.com/read/28918104/peripheral-blood-lymphocyte-to-monocyte-ratio-at-relapse-predicts-outcome-for-patients-with-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-in-the-rituximab-era
#16
Daisuke Katoh, Yotaro Ochi, Tomohiro Yabushita, Yuichiro Ono, Nobuhiro Hiramoto, Satoshi Yoshioka, Noboru Yonetani, Akiko Matsushita, Hisako Hashimoto, Shuichiro Kaji, Yukihiro Imai, Takayuki Ishikawa
BACKGROUND: Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis, even in the rituximab era. Several studies have reported the clinical importance of the peripheral blood lymphocyte-to-monocyte ratio (LMR) in various malignancies, including lymphoma. However, the prognostic value of the LMR in relapsed/refractory DLBCL has not been well evaluated. The purpose of the present study was to investigate whether the LMR at relapse can predict clinical outcomes for relapsed/refractory DLBCL patients treated with rituximab...
August 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28917680/effusive-constrictive-pericarditis-after-pericardiocentesis-incidence-associated-findings-and-natural-history
#17
Kye Hun Kim, William R Miranda, Larry J Sinak, Faisal F Syed, Rowlens M Melduni, Raul E Espinosa, Garvan C Kane, Jae K Oh
OBJECTIVES: This study sought to investigate the incidence, associated findings, and natural history of effusive-constrictive pericarditis (ECP) after pericardiocentesis. BACKGROUND: ECP is characterized by the coexistence of tense pericardial effusion and constriction of the heart by the visceral pericardium. Echocardiography is currently the main diagnostic tool in the assessment of pericardial disease, but limited data have been published on the incidence and prognosis of ECP diagnosed by echo-Doppler...
September 9, 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28917273/mechanisms-and-risk-factors-of-thrombosis-in-cancer
#18
REVIEW
Anna Falanga, Laura Russo, Viola Milesi, Alfonso Vignoli
The close relationship between cancer and thrombosis is known since more than a century. Venous thromboembolism (VTE) may be the first manifestation of an occult malignancy in an otherwise healthy individual. Cancer patients commonly present with abnormalities of laboratory coagulation tests, indicating an ongoing subclinical hypercoagulable condition. The results of laboratory tests demonstrate that a process of fibrin formation and removal parallels the development of malignancy, which is of particular interest since fibrin and other clotting products are important for both thrombogenesis and tumor progression...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28916184/role-of-the-il-12-il-35-balance-in-sj%C3%A3-gren-s-syndrome
#19
Olivier Fogel, Elodie Rivière, Raphaèle Seror, Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Jacques-Eric Gottenberg, Véronique Le Guern, Jean-Jacques Dubost, Joanne Nititham, Kimberly E Taylor, Philippe Chanson, Philippe Dieudé, Lindsey A Criswell, Bernd Jagla, Alice Thai, Michael Mingueneau, Xavier Mariette, Corinne Miceli-Richard
BACKGROUND: An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35. OBJECTIVE: To confirm the genetic association of IL-12A polymorphism and pSS and elucidate the involvement of the IL-12/IL-35 balance in pSS by functional studies...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28916002/characterization-of-immune-response-in-staphylococcus-aureus-chronically-infected-bovine-mammary-glands-during-active-involution
#20
Carolina S Andreotti, Celina Baravalle, Sofía C Sacco, Melisa Lovato, Elizabet A L Pereyra, María S Renna, Hugo H Ortega, Luis F Calvinho, Bibiana E Dallard
The aim of this study was to characterize the immune response in Staphylococcus aureus chronically infected bovine mammary glands during active involution. Twenty-one Holstein non-pregnant cows in late lactation either uninfected or with chronic naturally acquired S. aureus intramammary infections (IMI) were included in this study. Cows were slaughtered at 7, 14 and 21 d after cessation of milking and samples for immunohistochemical analysis were taken. Protein expression of toll-like receptor 2 (TLR2) and TLR4 was significantly higher in S...
October 2017: Comparative Immunology, Microbiology and Infectious Diseases
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