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https://www.readbyqxmd.com/read/28089042/molecular-screening-of-xerophilic-aspergillus-strains-producing-mycophenolic-acid
#1
Bello Mouhamadou, Lucile Sage, Sophie Périgon, Virginie Séguin, Valérie Bouchart, Patrick Legendre, Mathilde Caillat, Hayet Yamouni, David Garon
Mycophenolic acid (MPA) is the fungal secondary metabolite displaying several biological properties. Up to now, screening of fungal strains producing MPA has mainly been the result of the search of this molecule in their culture medium by chemical methods. Here we developed a molecular approach by targeting the expression level of the MpaC gene encoding the polyketide synthase, one of the key enzymes involved in the MPA synthesis. Thirty xerophilic Aspergillus strains were identified using the RNA polymerase II subunit and the β-tubulin genes...
February 2017: Fungal Biology
https://www.readbyqxmd.com/read/28076831/dosing-time-dependent-oxidative-effects-of-an-immunosuppressive-drug-mycophenolate-mofetil-on-rat-kidneys
#2
Ichrak Dridi, Wafa Ben-Cherif, Hassiba Chahdoura, Zohra Haouas, Mossadok Ben-Attia, Karim Aouam, Alain Reinberg, Naceur A Boughattas
This study investigates whether the toxicity in kidneys as well as oxidative stress varied according to the dosing time of an immunosuppressive agent "mycophenolate mofetil (MMF)" in Wistar Rat. 300mg/kg of MMF was injected by intraperitonal at four different circadian stages (1, 7, 13 and 19h after light onset, HALO). Rats were sacrificed after 3days, and the kidneys were removed for determination of oxidative stress and histological analysis. Biochemical variable (creatinine, urea) was performed. Statistical analysis showed that MMF administration at 7 HALO produced a renal toxicity assessed by the significant increase in both blood creatinine and urea and antioxidant activity assessed by malondialdehyde and protein carbonyl levels indicating an induction of lipid peroxidation in oxidative damage...
January 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28074365/determination-of-cytostatic-drugs-in-bes%C3%A3-s-river-ne-spain-and-comparison-with-predicted-environmental-concentrations
#3
Helena Franquet-Griell, Deborah Cornadó, Josep Caixach, Francesc Ventura, Silvia Lacorte
The number of cytostatic drugs used in cancer treatments is wide and increases every year; therefore, tools have been developed to predict their concentration in the environment to prioritize those for monitoring studies. In the present study, the predicted environmental concentrations (PECs) were calculated according to consumption data in Catalonia (NE Spain) for 2014. According to PECs and to the most widely reported compounds, 19 cytostatics were monitored in two sampling campaigns performed along the Besòs River...
January 10, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28051798/%C3%A2-conversion-to-mycophenolate-mofetil-monotherapy-in-liver-recipients-calcineurin-inhibitor-levels-are-key
#4
Blanca Norero, Carolina A Serrano, Alberto Sanchez-Fueyo, Ignacio Duarte, Javiera Torres, Mauricio Ocquetau, Francisco Barrera, Marco Arrese, Alejandro Soza, Carlos Benítez
 The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28038680/changes-in-plasma-cxcl4-levels-are-associated-with-improvements-in-lung-function-in-patients-receiving-immunosuppressive-therapy-for-systemic-sclerosis-related-interstitial-lung-disease
#5
Elizabeth R Volkmann, Donald P Tashkin, Michael D Roth, Philip J Clements, Dinesh Khanna, Daniel E Furst, Maureen Mayes, Julio Charles, Chi-Hong Tseng, Robert M Elashoff, Shervin Assassi
BACKGROUND: Increased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD in the context of a randomized controlled trial and to determine whether changes in CXCL4 levels in response to immunosuppression are associated with future progression of SSc-ILD...
December 30, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28025957/correlation-between-pharmacokinetics-of-tacrolimus-and-pharmacodynamics-on-nfat-regulated-gene-expression-in-stable-kidney-transplant-recipients%C3%A2
#6
Frieder Keller, Claudia Sommerer, Thomas Giese, Martin Zeier, Bernd Schröppel
Gene expression regulated by the transcription factor NFAT (nuclear factor of activated T-cells) has been proposed for monitoring the pharmacodynamic effect of calcineurin inhibitors. We aimed to correlate the pharmacokinetics of tacrolimus with the suppression of NFAT-regulated gene expression. Tacrolimus trough (C<sub>trough</sub>) and peak concentrations (C<sub>peak</sub>) were measured by LC-MS. The effect on NFAT-regulated gene expression at trough (E<sub>trough</sub>) and at peak levels (E<sub>peak</sub>) were determined by qRT-PCR...
February 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/27990481/increased-telomere-attrition-after-renal-transplantation-impact-of-antimetabolite-therapy
#7
Karin Luttropp, Louise Nordfors, Dagmara McGuinness, Lars Wennberg, Hannah Curley, Tara Quasim, Helena Genberg, John Sandberg, Isabella Sönnerborg, Martin Schalling, Abdul Rashid Qureshi, Peter Bárány, Paul G Shiels, Peter Stenvinkel
BACKGROUND: The uremic milieu exposes chronic kidney disease (CKD) patients to premature ageing processes. The impact of renal replacement therapy (dialysis and renal transplantation [RTx]) or immunosuppressive treatment regimens on ageing biomarkers has scarcely been studied. METHODS: In this study telomere length in whole blood cells was measured in 49 dialysis patients and 47 RTx patients close to therapy initiation and again after 12 months. Forty-three non-CKD patients were included as controls...
December 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27938774/a-48-year-old-man-with-leukopenia-jaundice-and-skin-rash-after-lung%C3%A2-transplantation
#8
Ali Ataya, Abhishek Biswas, Satish Chandrashekaran, Juan C Salgado, Steven S Goldstein, Amir M Emtiazjoo
A 48-year-old African-American male subject presented with progressive fatigue, jaundice, and new-onset leukopenia 12 weeks after undergoing bilateral lung transplantation for advanced pulmonary sarcoidosis. His transplant surgery and immediate posttransplantation course were uneventful. Induction immunosuppression included methylprednisolone 500 mg intraoperatively and basiliximab (anti-IL-2 monoclonal antibody) on days 0 and 4 after transplantation. His maintenance immunosuppression posttransplantation was prednisone 20 mg daily, tacrolimus with target tacrolimus levels 10 to 15 ng/mL, and mycophenolate mofetil 750 mg twice daily...
December 2016: Chest
https://www.readbyqxmd.com/read/27932154/successful-preemptive-kidney-transplantation-with-rituximab-induction-in-a-patient-with-focal-segmental-glomerulosclerosis-and-massive-nephrotic-syndrome-a-case-report
#9
A Kolonko, G Piecha, A Więcek
Primary focal segmental glomerulosclerosis (FSGS) recurs in 30% of patients receiving their first kidney transplant and often leads to graft loss. In the past, patients with FSGS and overt nephrotic syndrome rarely underwent transplantation. Rituximab (RTX), an anti-CD20-specific monoclonal antibody, was previously reported to be a valuable option in treating relapsing FSGS after kidney transplantation. We report here the first successful kidney transplantation in a young patient with primary FSGS and massive nephrotic syndrome treated with RTX induction...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27924728/synthesis-and-immunosuppressive-activity-of-new-mycophenolic-acid-derivatives
#10
Karina Pereira Barbieri, Lucas Dos Reis Ercolin, Thierry Louat, Marisa Campos Polesi, Chung Man Chin, Iracilda Carlos Zeppone, Jean Leandro Dos Santos
BACKGROUND: Immunosuppressive drugs are widely used to prevent and treat allograft rejection and autoimmune diseases. Mycophenolic acid (MPA) and its derivatives are currently one of the most prescribed immunosuppressive drugs; however, metabolic drawbacks and variable inter- and intrapatient responses limit its use. OBJECTIVE: In order to find out new safe and effective immunosuppressive compounds we report here the synthesis and pharmacological evaluation of hybrid MPA derivatives containing the thalidomide/phthalimide subunits...
December 7, 2016: Medicinal Chemistry
https://www.readbyqxmd.com/read/27919709/evaluation-of-anti-zika-virus-activities-of-broad-spectrum-antivirals-and-nih-clinical-collection-compounds-using-a-cell-based-high-throughput-screen-assay
#11
Robert S Adcock, Yong-Kyu Chu, Jennifer E Golden, Dong-Hoon Chung
Recent studies have clearly underscored the association between Zika virus (ZIKV) and severe neurological diseases such as microcephaly and Guillain-Barre syndrome. Given the historical complacency surrounding this virus, however, no significant antiviral screenings have been performed to specifically target ZIKV. As a result, there is an urgent need for a validated screening method and strategy that is focused on highlighting potential anti-ZIKV inhibitors that can be further advanced via rigorous validation and optimization...
February 2017: Antiviral Research
https://www.readbyqxmd.com/read/27914701/il-2-anti-il-2-complexes-ameliorate-lupus-nephritis-by-expansion-of-cd4-cd25-foxp3-regulatory-t%C3%A2-cells
#12
Ji-Jing Yan, Jae-Ghi Lee, Joon Young Jang, Tai Yeon Koo, Curie Ahn, Jaeseok Yang
Adoptive transfer of regulatory T cells (Tregs) can delay disease progression and reduce mortality in lupus-prone mice. Here, we tested whether complex (IL-2C) consisting of IL-2 and anti-IL-2 monoclonal antibody (JES6-1) ameliorates lupus nephritis by expanding Tregs as an alternative to problematic Treg infusion therapy. IL-2C treatment of NZB/W F1 mice induced an effective and sustained expansion of CD4(+)CD25(+)Foxp3(+) Tregs in both the kidneys and spleen along with decreased renal infiltration of T cells, B cells, and innate immune cells...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27900974/disseminated-mycobacteria-chelonae-infection-in-a-kidney-pancreas-transplant-recipient-a-case-report-and-review-of-the-literature
#13
Shafi Malik, Ananda Ghosh, Shahid Husain
A 40-year-old male with a long-standing history of type 1 diabetes with end-stage renal failure underwent combined kidney-pancreas (KP) transplant from a standard criteria donor. Post-operative course was uncomplicated with good primary function of both transplant grafts. Induction was with thymoglobulin and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and prednisolone. Nine weeks post-transplant, the patient developed dysfunction of both grafts. Panel reactive antibody testing revealed that the patient had developed a de novo donor-specific antibody and considering an antibody-mediated rejection the patient was treated with intravenous pulse methyl prednisone 500 mg ×3 doses, IV immunoglobulin 2 mg/kg in two divided doses, and ATG 7 mg/kg (total dose of 700 mg)...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27898598/pharmacokinetics-of-mycophenolic-acid-and-dose-optimization-in-children-after-intestinal-transplantation
#14
Caroline Barau, Antonio Mellos, Stéphanie Chhun, Florence Lacaille, Valérie Furlan
BACKGROUND: Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (MPS) are now commonly used in pediatric intestinal transplantation (Tx), but to date, no clear recommendations regarding the dosing regimen have been made in this population. The aim of this study was to determine the MMF/MPS dosage required to achieve an area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12) for mycophenolic acid (MPA) greater than 30 mg.h/L in children after intestinal transplantation...
November 28, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27896807/fdg-pet-ct-imaging-of-therapeutic-response-in-granulomatous-lymphocytic-interstitial-lung-disease-glild-in-common-variable-immunodeficiency-cvid
#15
S Jolles, E Carne, M Brouns, T El-Shanawany, P Williams, C Marshall, P Fielding
Common variable immunodeficiency (CVID) is the most common severe adult primary immunodeficiency and is characterized by a failure to produce antibodies leading to recurrent predominantly sinopulmonary infections. Improvements in the prevention and treatment of infection with immunoglobulin replacement and antibiotics have resulted in malignancy, autoimmune, inflammatory and lymphoproliferative disorders emerging as major clinical challenges in the management of patients who have CVID. In a proportion of CVID patients, inflammation manifests as granulomas that frequently involve the lungs, lymph nodes, spleen and liver and may affect almost any organ...
January 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27862344/diabetes-mellitus-after-kidney-transplantation-in-japanese-patients-the-japan-academic-consortium-of-kidney-transplantation-study
#16
Masayoshi Okumi, Kohei Unagami, Toshihito Hirai, Tomokazu Shimizu, Hideki Ishida, Kazunari Tanabe
OBJECTIVES: To clarify the incidence rate of post-transplant diabetes mellitus and associated risk factors in Japanese kidney transplant recipients, and to explore which treatment components are most effective in reducing post-transplant diabetes mellitus. METHODS: We analyzed 849 Japanese non-diabetic adult recipients who had undergone living kidney transplantation and had received tacrolimus-based immunosuppression from 1996 to 2013 with a median follow-up of 5 years...
November 11, 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/27861289/the-effect-of-asp2409-a-novel-cd86-selective-variant-of-ctla4-ig-on-renal-allograft-rejection-in-nonhuman-primates
#17
Shinsuke Oshima, Erik E Karrer, Yuka Kawato, Masashi Maeda, Hidehiko Fukahori, Susumu Tsujimoto, Jun Hirose, Koji Nakamura, Takanori Marui, Fujiko Takamura, Takahisa Noto, Steven J Chapin, Yasutomo Fujii, Margaret Neighbors, Sridhar Viswanathan, Bruce H Devens, Yasuyuki Higashi
BACKGROUND: Blockade of CD28-mediated T cell costimulation by a modified cytotoxic T lymphocyte-associated antigen 4 (CTLA4-Ig), belatacept, is a clinically effective immunosuppressive therapy for the prevention of renal allograft rejection. Use of belatacept-based calcineurin inhibitor-free immunosuppression, however, has demonstrated an increased frequency of cellular rejection episodes and immunosuppression-related safety issues relative to conventional regimens. Furthermore, belatacept typically requires infusion for its administration chronically, which may present an inconvenience to patients...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27852609/il-17-mediates-neutrophil-infiltration-and-renal-fibrosis-following-recovery-from-ischemia-reperfusion-compensatory-role-of-natural-killer-cells-in-athymic-rats
#18
Purvi Mehrotra, Jason A Collett, Seth McKinney, Jackson Stevens, Carlie M Ivancic, David P Basile
T cells have been implicated in the pathogenesis of AKI as well as its progression to CKD. Previous studies suggest that Th17 cells participates during the AKI to CKD transition and inhibition of T cell activity by mycophenolate mofetil (MMF) or losartan attenuates the development of fibrosis following AKI. We hypothesized that T cell deficient rats may have reduced levels of IL-17 cytokine leading to decreased fibrosis following AKI. Renal I/R was performed on T cell deficient athymic rats (Foxn1rnu-/rnu-) and control euthymic rats (Foxn1rnu-/+) and CKD progression was hastened by unilateral nephrectomy at Day 33 and subsequent exposure to 4...
November 16, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27798157/cd40-mediated-nf-%C3%AE%C2%BAb-activation-in-b-cells-is-increased-in-multiple-sclerosis-and-modulated-by-therapeutics
#19
Ding Chen, Sara J Ireland, Gina Remington, Enrique Alvarez, Michael K Racke, Benjamin Greenberg, Elliot M Frohman, Nancy L Monson
CD40 interacts with CD40L and plays an essential role in immune regulation and homeostasis. Recent research findings, however, support a pathogenic role of CD40 in a number of autoimmune diseases. We previously showed that memory B cells from relapsing-remitting multiple sclerosis (RRMS) patients exhibited enhanced proliferation with CD40 stimulation compared with healthy donors. In this study, we used a multiparameter phosflow approach to analyze the phosphorylation status of NF-κB and three major MAPKs (P38, ERK, and JNK), the essential components of signaling pathways downstream of CD40 engagement in B cells from MS patients...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27790959/igg4-related-syndrome-another-multiorgan-disease-in-the-interest-field-of-internal-medicine
#20
Antonino Tuttolomondo, Irene Simonetta, Domenico Di Raimondo, Tiziana Di Chiara, Roberta Conigliaro, Francesca Corpora, Valerio Vassallo, Antonio Pinto
BACKGROUND: IgG4-related disease is a rare, clinical and pathologic disease entity of unknown etiology. Its main features are increased serum concentrations of IgG4 > 1,35 g/l, lymphocyte and IgG4+plasma-cell infiltration within tissues, fibrosis or sclerosis. The classical presentation of IgG4-RSD is pancreatitis which is combined with the involvement of biliary ducts in 74 percent of patients. Extrapancreatic manifestations include: abdominal or mediastinal lymphadenopathy; the involvement of salivary glands and lacrimal glands, kidneys, lung, retroperitoneum...
2016: Current Pharmaceutical Design
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