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https://www.readbyqxmd.com/read/28818275/electromagnetic-fields-may-act-via-calcineurin-inhibition-to-suppress-immunity-thereby-increasing-risk-for-opportunistic-infection-conceivable-mechanisms-of-action
#1
P R Doyon, O Johansson
While a good number of studies have demonstrated that modern, man-made ambient electromagnetic fields can have both stimulatory and inhibitory effect on immune system function, the precise mechanisms have yet to be completely elucidated. It is hypothesized here that, depending on the parameters, one of the means by which long-term electromagnetic field exposure has the potential to eventually lead to immunosuppression is via downstream inhibition of the enzyme calcineurin - a protein phosphatase, which activates the T-cells of the immune system and can be blocked by pharmaceutical agents...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28815305/predictors-of-early-mortality-after-rabbit-antithymocyte-globulin-as-first-line-treatment-in-severe-aplastic-anemia
#2
Elias H Atta, Carlos B L Lima, Danielle S P Dias, Diego V Clé, Mariana M Bonduel, Gabriela B Sciuccati, Larissa A Medeiros, Michel M Oliveira, Marco A Salvino, Marlene P Garanito, Patricia B Blum Fonseca, Sara Teresinha O Saad, Rodrigo T Calado, Phillip Scheinberg
Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine...
August 16, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28807916/inhibition-of-calcineurin-or-impdh-exerts-moderate-to-potent-antiviral-activity-against-norovirus-replication
#3
Wen Dang, Yuebang Yin, Yijin Wang, Wenshi Wang, Junhong Su, Dave Sprengers, Luc J W van der Laan, Krzysztof Felczak, Krzysztof W Pankiewicz, Kyeong-Ok Chang, Marion P G Koopmans, Herold J Metselaar, Maikel P Peppelenbosch, Qiuwei Pan
Norovirus is a major cause of acute gastroenteritis worldwide and has emerged as an important issue of chronic infection in transplantation patients. Since no approved antiviral is available, we evaluated the effects of different immunosuppressants and ribavirin on norovirus and explored their mechanism-of-actions by using a human norovirus (HuNV) replicon-harboring model and a surrogate murine norovirus (MNV) infectious model. Roles of corresponding drug targets were investigated by gain- or loss-of-function approaches...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807082/hearing-status-in-patients-with-rheumatoid-arthritis
#4
A Ahmadzadeh, M Daraei, M Jalessi, A A Peyvandi, E Amini, L A Ranjbar, A Daneshi
OBJECTIVE: Rheumatoid arthritis is thought to induce conductive hearing loss and/or sensorineural hearing loss. This study evaluated the function of the middle ear and cochlea, and the related factors. METHODS: Pure tone audiometry, speech reception thresholds, speech discrimination scores, tympanometry, acoustic reflexes, and distortion product otoacoustic emissions were assessed in rheumatoid arthritis patients and healthy volunteers. RESULTS: Pure tone audiometry results revealed a higher bone conduction threshold in the rheumatoid arthritis group, but there was no significant difference when evaluated according to the sensorineural hearing loss definition...
August 15, 2017: Journal of Laryngology and Otology
https://www.readbyqxmd.com/read/28804552/in-vivo-opening-of-the-mitochondrial-permeability-transition-pore-in-a-rat-model-of-ventricular-fibrillation-and-closed-chest-resuscitation
#5
Iyad M Ayoub, Jeejabai Radhakrishnan, Raúl J Gazmuri
Opening of the mitochondrial permeability transition pore (mPTP) is considered central to reperfusion injury. Yet, most of our knowledge comes from observations in isolated mitochondria, cells, and organs. We used a rat model of ventricular fibrillation (VF) and closed-chest resuscitation to examine whether the mPTP opens in vivo and whether cyclosporine A (CsA) attenuates the associated myocardial injury. Two series of 26 and 18 rats each underwent 10 minutes of untreated VF before attempting resuscitation...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28797782/predictors-for-permanent-discontinuation-of-systemic-immunosuppression-in-severely-affected-chronic-graft-versus-host-disease-patients
#6
Lauren M Curtis, Filip Pirsl, Seth M Steinberg, Sandra A Mitchell, Kristin Baird, Edward W Cowen, Jacqueline Mays, Nataliya P Buxbaum, Dominique C Pichard, Annie Im, Daniele Avila, Tiffani Taylor, Daniel H Fowler, Ronald E Gress, Steven Z Pavletic
Predicting the duration of systemic therapy in patients with chronic graft-versus-host disease (cGVHD) is of critical clinical importance when counseling patients and for treatment planning. CGVHD characteristics associated with this outcome have not been studied in severely affected patients. The National Institutes of Health (NIH) cGVHD scoring provides a standardized set of organ severity measures which could represent clinically useful and reproducible predictive characteristics. We analyzed 227 previously treated patients most with moderate (n=54) or severe (n=170) cGVHD defined by NIH criteria who were prospectively enrolled in a natural history protocol (NCT00092235)...
August 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28796779/dose-and-timing-of-injections-for-effective-cyclosporine-a-pretreatment-before-renal-ischemia-reperfusion-in-mice
#7
Sandrine Lemoine, Bruno Pillot, Lionel Augeul, Maud Rabeyrin, Annie Varennes, Gabrielle Normand, Delphine Baetz, Michel Ovize, Laurent Juillard
BACKGROUND: There is experimental evidence that lethal ischemia-reperfusion injury (IRI) is largely due to mitochondrial permeability transition pore (mPTP) opening, which can be prevented by cyclosporine A (CsA). The aim of our study is to show that a higher dose of CsA (10 mg/kg) injected just before ischemia or a lower dose of CsA (3 mg/kg) injected further in advance of ischemia (1 h) protects the kidneys and improves mitochondrial function. METHODS: All mice underwent a right unilateral nephrectomy followed by 30 min clamping of the left renal artery...
2017: PloS One
https://www.readbyqxmd.com/read/28795694/correlating-the-potentiometric-selectivity-of-cyclosporin-based-electrodes-with-binding-patterns-obtained-from-electrospray-ionization-mass-spectrometry
#8
Elsayed M Zahran, Ki-Jung Paeng, Ibrahim H A Badr, David Hume, Bert C Lynn, R Daniel Johnson, Leonidas G Bachas
Electrospray ionization mass spectrometry ESI-MS is a powerful technique for the characterization of macromolecules and their noncovalent binding with guest ions. We herein evaluate the feasibility of using ESI-MS as a screening tool for predicting potentiometric selectivities of ionophores. Ion-selective electrodes based on the cyclic peptide, cyclosporin A, were developed, and their potentiometric selectivity pattern was evaluated. Optimized electrodes demonstrated near-Nernstian slopes with micromolar detection limits toward calcium...
August 10, 2017: Analyst
https://www.readbyqxmd.com/read/28795147/impact-of-the-trough-level-of-calcineurin-inhibitor-on-the-prevalence-of-donor-specific-human-leukocyte-antigen-antibodies-during-long-term-follow-up-after-pediatric-liver-transplantation-antibody-strength-and-complement-binding-ability
#9
Kazuaki Tokodai, Shigehito Miyagi, Chikashi Nakanishi, Yasuyuki Hara, Wataru Nakanishi, Masafumi Goto, Michiaki Unno, Takashi Kamei
BACKGROUND: In pediatric patients, long-term immunosuppression after liver transplantation (LT) is typically minimal. However, posttransplant donor-specific HLA antibodies (DSAs) may be prevalent under these conditions. Here, we evaluated the effects of minimized calcineurin inhibitor (CNI) on DSA development to assess the validity of minimized/withdrawn immunosuppression. METHODS: We retrospectively examined 66 patients who underwent pediatric LT at our institution between July 1991 and October 2013...
August 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28795098/data-on-administration-of-cyclosporine-nicorandil-metoprolol-on-reperfusion-related-outcomes-in-st-segment-elevation-myocardial-infarction-treated-with-percutaneous-coronary-intervention
#10
Gianluca Campo, Rita Pavasini, Giampaolo Morciano, Michael A Lincoff, Michael C Gibson, Masafumi Kitakaze, Jacob Lonborg, Amrita Ahluwalia, Hideki Ishii, Michael Frenneaux, Michel Ovize, Marcello Galvani, Dan Atar, Borja Ibanez, Giampaolo Cerisano, Simone Biscaglia, Brandon J Neil, Masanori Asakura, Thomas Engstrom, Daniel A Jones, Dana Dawson, Roberto Ferrari, Paolo Pinton, Filippo Ottani
Mortality and morbidity in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) are still high [1]. A huge amount of the myocardial damage is related to the mitochondrial events happening during reperfusion [2]. Several drugs directly and indirectly targeting mitochondria have been administered at the time of the PCI and their effect on fatal (all-cause mortality, cardiovascular (CV) death) and non fatal (hospital readmission for heart failure (HF)) outcomes have been tested showing conflicting results [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]...
October 2017: Data in Brief
https://www.readbyqxmd.com/read/28795058/functional-histopathological-and-immunohistichemical-assessments-of-cyclosporine-a-on-sciatic-nerve-regeneration-using-allografts-a-rat-sciatic-nerve-model
#11
Amir Amniattalab, Rahim Mohammadi
OBJECTIVES: To study the functional, histopathological and immunohistochemical effect of cyclosporine A on sciatic nerve regeneration using allografts in a rat sciatic nerve model. METHODS: Thirty male white Wistar rats were divided into three experimental groups (n = 10), randomly: Normal control group (NC), allograft group (ALLO), CsA treated group (ALLO/ CsA). In NC group left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured...
July 2017: Bulletin of Emergency and Trauma
https://www.readbyqxmd.com/read/28791279/pneumocystis-jirovecii-pneumonia-in-pediatric-inflammatory-bowel-disease-a-case-report-and-literature-review
#12
Sally J Lawrence, Manish Sadarangani, Kevan Jacobson
Immunosuppressive therapy is a known risk factor for opportunistic infections. We report the first case of severe Pneumocystis jirovecii infection requiring intensive care in a pediatric patient with inflammatory bowel disease (IBD). The literature was reviewed and there were 92 reported cases of Pneumocystis pneumonia (PCP) in patients with IBD. Most sources were case reports and there was likely reporting bias toward patients receiving immunomodulators, anti-tumor necrosis factor (anti-TNF) therapy, and those who died...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28790800/clinical-utility-of-cyclosporine-csa-ophthalmic-emulsion-0-05-for-symptomatic-relief-in-people-with-chronic-dry-eye-a-review-of-the-literature
#13
REVIEW
Michelle K Rhee, Francis S Mah
To review the literature on the efficacy of cyclosporine (CsA) ophthalmic emulsion 0.05% on symptomatic relief in chronic dry eye disease. There is consistent evidence of objective improvements in chronic dry eye disease (Schirmer score, corneal and interpalpebral dye staining, and tear breakup time) with CsA, but variable results with symptomatic improvement, possibly due to patient tolerance of CsA, similar comforting effect with artificial tears and CsA vehicle, and the inherent subjective nature of symptom monitoring and analysis...
2017: Clinical Ophthalmology
https://www.readbyqxmd.com/read/28790108/cyclophilin-a-maintains-glioma-initiating-cell-stemness-by-regulating-wnt-%C3%AE-catenin-signaling
#14
Guangzhi Wang, Jia Shen, Jiahang Sun, Zhenfeng Jiang, Jiabing Fan, Hongjun Wang, Shan Yu, Yu Long, Yi Liu, HOngbo Bao, Kelvin X Zhang, Ke Han, Min-Wei Zhu, Yongri Zheng, Zhiguo Lin, Chuanlu Jiang, Mian Guo
PURPOSE: Glioma-initiating cells (GICs) are glioma stem-like cells that contribute to glioblastoma (GBM) development, recurrence, and resistance to chemotherapy and radiotherapy. They have recently become the focus of novel treatment strategies. Cyclophilin A (CypA) is a cytosolic protein that belongs to the peptidyl-prolyl isomerase (PPIase) family and the major intracellular target of the immunosuppressive drug cyclosporin A (CsA). In this study, we investigate the functions of CypA and its mechanism of action in GICs' development...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28789840/cyclophilin-inhibitor-nim811-ameliorates-experimental-allergic-encephalomyelitis
#15
Zi L Huang, Darshan Pandya, Daisy K Banta, Maryam S Ansari, Unsong Oh
Cyclophilins have diverse functions that may affect the course of central nervous system (CNS) inflammatory disorders. Anti-inflammatory and neuroprotective mechanisms may be targeted by inhibition of cyclophilin A-dependent and cyclophilin D-dependent functions, respectively. We tested the effect of cyclophilin inhibition on CNS inflammation by administering N-methyl-4-isoleucine-cyclosporin (NIM811) to mice undergoing experimental allergic encephalomyelitis (EAE). Treatment with NIM811 resulted in significant reduction of EAE clinical severity...
August 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28777375/inhibition-of-bcl-xl-prevents-pro-death-actions-of-%C3%AE-n-bcl-xl-at-the-mitochondrial-inner-membrane-during-glutamate-excitotoxicity
#16
Han-A Park, Pawel Licznerski, Nelli Mnatsakanyan, Yulong Niu, Silvio Sacchetti, Jing Wu, Brian M Polster, Kambiz N Alavian, Elizabeth A Jonas
ABT-737 is a pharmacological inhibitor of the anti-apoptotic activity of B-cell lymphoma-extra large (Bcl-xL) protein; it promotes apoptosis of cancer cells by occupying the BH3-binding pocket. We have shown previously that ABT-737 lowers cell metabolic efficiency by inhibiting ATP synthase activity. However, we also found that ABT-737 protects rodent brain from ischemic injury in vivo by inhibiting formation of the pro-apoptotic, cleaved form of Bcl-xL, ΔN-Bcl-xL. We now report that a high concentration of ABT-737 (1 μM), or a more selective Bcl-xL inhibitor WEHI-539 (5 μM) enhances glutamate-induced neurotoxicity while a low concentration of ABT-737 (10 nM) or WEHI-539 (10 nM) is neuroprotective...
August 4, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28776332/sirolimus-and-metformin-synergistically-inhibits-colon-cancer-in-vitro-and-in-vivo
#17
Nadiar Mussin, Seung Cheol Oh, Kwang Woong Lee, Min Young Park, Sooin Seo, Nam Joon Yi, Hyeyoung Kim, Kyung Chul Yoon, Sung Woo Ahn, Hyo Sin Kim, Suk Kyun Hong, Dong Kyu Oh, Kyung Suk Suh
We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA)...
September 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28774843/self-assembling-polymeric-nanocarriers-to-target-inflammatory-lesions-in-ulcerative-colitis
#18
Herve Courthion, Thibault Mugnier, Christel Rousseaux, Michael Möller, Robert Gurny, Doris Gabriel
We have developed a self-assembling polymeric nanocarrier to deliver the potent immunosuppressive drug Cyclosporine A (CsA) to inflammatory lesions in ulcerative colitis (UC) patients. Our nanocarrier has a high drug loading capacity and efficiently targets its CsA payload to the diseased tissue after local administration. Tissue drug levels were several orders of magnitude higher in animals suffering from a trinitrobenzene-sulfonic acid (TNBS) - induced colitis, compared to healthy control animals; no drug was detectable in the plasma, underlining the localized delivery strategy...
July 31, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28774273/thrombotic-microangiopathy-associated-with-valproic-acid-toxicity
#19
Sean A Hebert, Timothy P Bohan, Christian L Erikson, Rita D Swinford
BACKGROUND: Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA...
August 3, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28770513/selective-interleukin-23-p19-inhibition-another-game-changer-in-psoriasis-focus-on-risankizumab
#20
Tiago Torres
The history of psoriasis treatment has been marked by several milestones. Corticosteroids, cyclosporine, tumor necrosis factor alpha (TNF-α) inhibitors and, more recently, interleukin (IL)-17A inhibitors have revolutionized the treatment of psoriasis, each in its own way and time. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis and selective IL-23p19 inhibition may bring several advantages with respect to IL-12/23p40 inhibition, or distal blockade of IL-17A or its receptor...
August 2, 2017: Drugs
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