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https://www.readbyqxmd.com/read/28935695/confirmed-efficacy-of-etoposide-and-dexamethasone-in-hlh-treatment-long-term-results-of-the-cooperative-hlh-2004-study
#1
Elisabet Bergsten, AnnaCarin Horne, Maurizio Aricó, Itziar Astigarraga, R Maarten Egeler, Alexandra H Filipovich, Eiichi Ishii, Gritta Janka, Stephan Ladisch, Kai Lehmberg, Kenneth L McClain, Milen Minkov, Scott Montgomery, Vasanta Nanduri, Diego Rosso, Jan-Inge Henter
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% CI, 48-60%), systemic therapy included etoposide, dexamethasone and, from week nine, cyclosporine A (CSA). HSCT was indicated in patients with familial/genetic, relapsing, or severe and persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity...
September 21, 2017: Blood
https://www.readbyqxmd.com/read/28935006/novel-h-shunt-venovenous-bypass-for-liver-transplantation-in-cynomolgus-macaques
#2
Yojiro Kato, Adam D Griesemer, Anette Wu, Hugo P Sondermeijer, Joshua I Weiner, Raimon Duran-Struuck, Mercedes Martinez, Andrea R Slate, Alexander Romanov, Jay H Lefkowitch, Megan Sykes, Tomoaki Kato
Cynomolgus monkeys are often used in preclinical transplantation research. Performing liver transplantation in cynomolgus monkeys is challenging because they poorly tolerate portal vein clamping during the anhepatic phase. Finding an alternative to portal vein clamping is necessary before preclinical liver transplant models can be performed with reliable outcomes. We used 3 different techniques to perform 5 liver transplants in male cynomolgus macaques (weight, 7.4-10.8 kg; mismatched for MHC I and II; matched for ABO)...
October 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28932875/-severe-cutaneous-drug-reactions-in-children
#3
REVIEW
M Mockenhaupt
Among severe drug reactions in children, besides Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), a specific form of hypersensitivity syndrome which is nowadays known as "drug reaction with eosinophilia and systemic symptoms" (DRESS) has to be mentioned. Whereas SJS/TEN is considered one reaction entity of different severity, DRESS has to be distinguished from SJS/TEN but also from other severe exanthems due to multiorgan involvement. Although SJS/TEN is generally referred to as a drug reaction, only about 75% of all cases are actually caused by medications and in children it is only about 50%...
September 20, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28930797/optimizing-the-safety-profile-of-everolimus-by-delayed-initiation-in-de-novo-heart-transplant-recipients-results-of-the-prospective-randomized-study-everheart
#4
Luciano Potena, Carlo Pellegrini, Francesco Grigioni, Cristiano Amarelli, Ugolino Livi, Massimo Maccherini, Gabriella Masciocco, Giuseppe Faggian, Paola Lilla Della Monica, Gino Gerosa, Nicola Marraudino, Marco Corda, Massimo Boffini
BACKGROUND: Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. METHODS: This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion (PCEs), pleural effusion (PLEs) needing drainage, and renal insufficiency events (estimated glomerular filtration rate [eGFR] ≤30/mL/min/1...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28928138/progressive-and-preferential-cellular-accumulation-of-hydrophobic-bile-acids-induced-by-cholestatic-drugs-is-associated-with-inhibition-of-their-amidation-and-sulfation
#5
Ahmad Sharanek, Audrey Burban, Lydie Humbert, Christiane Guguen-Guillouzo, Dominique Rainteau, Andre Guillouzo
Drug-induced intrahepatic cholestasis is characterized by cellular accumulation of bile acids (BA) whose mechanisms remain poorly understood. The present study aimed to analyze early and progressive alterations of BA profiles induced by cyclosporine A, chlorpromazine, troglitazone, tolcapone, trovafloxacin and tacrolimus after 4h, 24h and 6 daily treatments of differentiated HepaRG cells. In BA-free medium the potent cholestatic drugs, cyclosporine A, chlorpromazine and troglitazone, reduced endogenous BA synthesis after 24h, while the rarely cholestatic drugs, tolcapone, trovafloxacin and tacrolimus, reduced BA synthesis only after 6 days...
September 19, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28927426/the-acid-sensing-ion-channel-asic2-promotes-invasion-and-metastasis-of-colorectal-cancer-under-acidosis-by-activating-the-calcineurin-nfat1-axis
#6
Zhi-Hang Zhou, Jin-Wen Song, Wen Li, Xue Liu, Liu Cao, Lu-Ming Wan, Ying-Xia Tan, Shou-Ping Ji, Yu-Mei Liang, Feng Gong
BACKGROUND: The tumor acidic microenvironment, a common biochemical event in solid tumors, offers evolutional advantage for tumors cells and even enhances their aggressive phenotype. However, little is known about the molecular mechanism underlying the acidic microenvironment-induced invasion and metastasis. METHODS: We examined the expression of the acid-sending ion channel (ASIC) family members after acidic exposure using RT-PCR and immunofluoresence. Gene manipulation was applied to reveal the potential of ASIC2 on invasion, proliferation, colony formation of colorectal cancer (CRC)...
September 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28925592/defining-a-microrna-mrna-interaction-map-for-calcineurin-inhibitor-induced-nephrotoxicity
#7
Christopher J Benway, John Iacomini
Calcineurin inhibitors induce nephrotoxicity through poorly understood mechanisms thereby limiting their use in transplantation and other diseases. Here we define a microRNA (miRNA)-messenger RNA (mRNA) interaction map that facilitates exploration into the role of miRNAs in cyclosporine-induced nephrotoxicity (CIN) and the gene pathways they regulate. Using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we isolated RNAs associated with Argonaute 2 in the RNA-Induced Silencing Complex (RISC) of cyclosporine A (CsA) treated and control human proximal tubule cells and identified mRNAs undergoing active targeting by miRNAs...
September 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28925576/is-there-an-increased-risk-of-cervical-neoplasia-in-atopic-dermatitis-patients-treated-with-oral-immunosuppressive-drugs
#8
F M Garritsen, R H M Verheijen, C G Gerestein, A D van Zuilen, J A F Oosterhaven, M van Dijk, C A F Bruijnzeel-Koomen, M L Schuttelaar, M S de Bruin-Weller
BACKGROUND: Oral immunosuppressive drugs are frequently prescribed in young women with atopic dermatitis (AD). Immunocompromised patients may have a higher risk of developing high risk HPV infections, CIN and cervical carcinoma. Most literature on patients using oral immunosuppressive drugs is available in organ transplant patients. Literature on the risk of developing cervical carcinoma in AD patients treated with oral immunosuppressive drugs is lacking. At this moment there is no clear guideline/consensus on this topic, but in daily practice, questions arise concerning whether this risk is increased and whether more intensive screening in women using immunosuppressive drugs should take place...
September 19, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28924464/the-relationship-between-mortality-of-lung-transplant-recipients-and-serum-cyclosporine-levels-joint-modeling-of-time-to-event-data-and-longitudinal-data
#9
F S Hosseini-Baharanchi, E Hajizadeh, A R Baghestani, K Najafzadeh
BACKGROUND: Lung transplantation (LTx) is a well-accepted treatment that can prolong survival of patients with advanced lung disease. OBJECTIVE: To evaluate the association between serum cyclosporine level (SCL) pattern and mortality of LTx recipients. METHODS: This retrospective cohort study included 1019 observations on 38 patients who underwent LTx in Masih Daneshvari Hospital from 2000 to 2013. The analysis applied a joint model with shared random effects...
2017: International Journal of Organ Transplantation Medicine
https://www.readbyqxmd.com/read/28923870/associations-between-voriconazole-therapeutic-drug-monitoring-toxicity-and-outcome-in-liver-transplant-patients-an-observational-study
#10
Zahra Hashemizadeh, Parisa Badiee, Seyed Ali Malekhoseini, Hadi Raeisi Shahraki, Bita Geramizadeh, Hashem Montaseri
The aim of this study was to investigate the variability of voriconazole plasma level and its relationship with clinical outcomes and adverse events, among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included and voriconazole trough levels were quantified by the validated high-performance liquid chromatography method. Cytochrome P450 genotypes of CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923621/extended-spectrum-beta-lactamase-producing-enterobacteriaceae-related-urinary-tract-infection-in-kidney-transplant-recipients-risk-factors-treatment-and-long-term-outcome
#11
S Brakemeier, S I Taxeidi, B Zukunft, D Schmidt, J Gaedeke, M Dürr, S Hansen, K Budde
BACKGROUND: Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) has risen in kidney transplant (KT) patients, with no long-term data so far on graft function or survival. METHODS: KT patients with ESBL-E-positive urine culture were retrospectively analyzed regarding initial adequate antimicrobial therapy, recurrent infection, transplant function, and survival compared with an ESBL-E-negative KT control cohort. RESULTS: ESBL-E-positive KT patients (n = 93) were older (55...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923619/ten-year-follow-up-of-pharmacokinetics-guided-very-early-cyclosporine-minimization-synchronized-with-everolimus-initiation-in-de-novo-kidney-transplantation
#12
V Sumethkul, P Tankee, S Worawichawong, S Jirasiritham
BACKGROUND: Minimization of calcineurin inhibitor (CNI) from the 1st week after kidney transplantation (KT) may reduce the risk of CNI nephrotoxicity. METHODS: Ten de novo KT recipients who received full exposure cyclosporine (CsA) and prednisolone as initial therapy were enrolled. Initial CsA minimization was 50% and started at day 7 after KT. This was synchronized with everolimus (EVL) initiation. Target trough level of EVL was 3-8 ng/mL. Pharmacokinetics studies of CsA and EVL were studied at week 4...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28921848/interconversion-rates-between-conformational-states-as-rationale-for-the-membrane-permeability-of-cyclosporines
#13
Jagna Witek, Max Mühlbauer, Bettina G Keller, Markus Blatter, Axel Meissner, Trixie Wagner, Sereina Riniker
Cyclic peptides have regained interest as potential inhibitors of challenging targets, but have often a low bioavailability. The natural product cyclosporine A (CsA) is the textbook exception. Despite its size and polar backbone it is able to passively cross membranes. This ability is hypothesized to be due to a conformational change from the low-energy conformation in water to a "congruent" conformation that is populated both in water and inside the membrane. Here, we use a combination of NMR measurements and kinetic models based on molecular dynamics simulations to rationalize the difference in the membrane permeability of cyclosporine E (CsE) and CsA...
September 17, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28921505/nfatc1-activation-by-dna-hypomethylation-in-chronic-lymphocytic-leukemia-correlates-with-clinical-staging-and-can-be-inhibited-by-ibrutinib
#14
Christine Wolf, Angela Garding, Katharina Filarsky, Jasmin Bahlo, Sandra Robrecht, Natalia Becker, Manuela Zucknick, Arefeh Rouhi, Anja Weigel, Rainer Claus, Dieter Weichenhan, Barbara Eichhorst, Kirsten Fischer, Michael Hallek, Florian Kuchenbauer, Christoph Plass, Hartmut Döhner, Stephan Stilgenbauer, Peter Lichter, Daniel Mertens
B cell receptor (BCR) signaling is key for survival of chronic lymphocytic leukemia (CLL) cells, and BCR signaling inhibitors are clinically active. However, relapse and resistance to treatment require novel treatment options. In order to detect novel candidate therapeutic targets, we performed a genome-wide DNA methylation screen with custom arrays and identified aberrant promoter DNA methylation in 2192 genes. The transcription factor NFATC1 that is a downstream effector of BCR signaling was among the top hypomethylated genes and was concomitantly transcriptionally upregulated in CLL...
September 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28919705/new-insight-into-the-pathogenesis-of-nail-psoriasis-and-overview-of-treatment-strategies
#15
REVIEW
Alessandra Ventura, Mauro Mazzeo, Roberta Gaziano, Marco Galluzzo, Luca Bianchi, Elena Campione
Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population. The prevalence of nail involvement in psoriasis patients varies between 15% and 79%. While the nails represent a small portion of the body surface area, psoriasis in these areas can have a disproportionate influence on a patient's physical and psychosocial activities. Differential diagnosis between an onychomycosis and a psoriatic nail could be challenging; nevertheless, coexistence of onychomycosis and nail psoriasis also occurs and both are common disorders in the general population...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919180/development-of-a-cyclosporin-a-derivative-with-excellent-anti-hepatitis-c-virus-potency
#16
Jiping Fu, Christopher Becker, Li Cao, Michael Capparelli, Regis Denay, Roger Fujimoto, Yu Gai, Zhaobo Gao, Christian Guenat, Subramanian Karur, Hongyong Kim, Weikuan Li, Xiaolin Li, Wei Li, Thomas Lochmann, Amy Lu, Peichao Lu, Alexandre Luneau, Nicole Meier, Wosenu Mergo, Simon Ng, David Parker, Yunshan Peng, Bernard Riss, Alexey Rivkin, Silvio Roggo, Harald Schroeder, Friedrich Schuerch, Robert L Simmons, Feng Sun, Zachary K Sweeney, Meiliana Tjandra, Michael Wang, Ruidong Wang, Andrew H Weiss, Nicolas Wenger, Quanbing Wu, Xin Xiong, Su Xu, Wenjian Xu, Aregahegn Yifru, Jibin Zhao, Jianguang Zhou, Christian Zürcher, Fabrice Gallou
Synthetic modification of cyclosporin A at P3-P4 positions led to the discovery of NIM258, a next generation cyclophilin inhibitor with excellent anti-hepatitis C virus potency, with decreased transporter inhibition, and pharmacokinetics suitable for coadministration with other drugs. Herein is disclosed the evolution of the synthetic strategy to from the original medicinal chemistry route, designed for late diversification, to a convergent and robust development synthesis. The chiral centers in the P4 fragment were constructed by an asymmetric chelated Claisen rearrangement in the presence of quinidine as the chiral ligand...
September 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28916431/cyclosporine-for-chronic-spontaneous-urticaria-a-meta-analysis-and-systematic-review
#17
Kanokvalai Kulthanan, Pichanee Chaweekulrat, Chulaluk Komoltri, Saowalak Hunnangkul, Papapit Tuchinda, Leena Chularojanamontri, Marcus Maurer
BACKGROUND: Despite widely recommended usage of cyclosporine A (CsA) in chronic spontaneous urticaria (CSU), there is no meta-analysis concerning its efficacy and safety. OBJECTIVE: To meta-analyze and review the efficacy and safety of CsA in CSU. METHODS: Efficacy was assessed by the relative change in urticaria activity score at 4 weeks and response rates at 4, 8, and 12 weeks. Safety was assessed by analyzing the number of patients with 1 or more adverse event...
September 12, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28915452/bk-virus-replication-in-renal-transplant-recipients-analysis-of-potential-risk-factors-may-contribute-in-reactivation
#18
Mohammad Shenagari, Ali Monfared, Hadise Eghtedari, Aydin Pourkazemi, Tolou Hasandokht, Masoud Khosravi, Babak Asharfkhani
BACKGROUND: Considering the increasing problem of BK virus infection during post renal transplant surveillance, it is necessary to distinguish the main risk factors leading to reactivation of latent BK virus. Up to now, some probable risk factors have been investigated in some studies, but the results have been confusing and contradictory. OBJECTIVES: The goal of the present study was to determine the frequency and potential risk factors that may play a role in BK polyomavirus reactivation and nephropathy...
September 8, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28914989/encapsulating-active-pharmaceutical-ingredients-in-self-assembling-adamantanes-with-short-dna-zippers
#19
Clemens Richert, Helmut Griesser, Alexander Schwenger
Formulating pharmaceutically active ingredients for drug delivery is a challenge. There is a need for new drug delivery systems that take up therapeutic molecules and release them into biological systems. We propose a novel mode of encapsulation that involves matrices formed through co-assembly of drugs with adamantane hybrids that feature four CG dimers as sticky ends. Such adamantanes are accessible via inexpensive solution-phase syntheses, and the resulting materials show attractive properties for controlled release...
September 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28913986/chronic-spontaneous-urticaria-pathogenesis-and-treatment-considerations
#20
REVIEW
Allen P Kaplan
The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H₁-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step...
November 2017: Allergy, Asthma & Immunology Research
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