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Calcineurin inhibitors

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https://www.readbyqxmd.com/read/29321815/circulating-plasma-microrna-profiling-in-patients-with-polymyositis-dermatomyositis-before-and-after-treatment-mirna-may-be-associated-with-polymyositis-dermatomyositis
#1
Takuya Hirai, Keigo Ikeda, Hiroshi Tsushima, Maki Fujishiro, Kunihiro Hayakawa, Yuko Yoshida, Shinji Morimoto, Ken Yamaji, Yoshinari Takasaki, Kenji Takamori, Naoto Tamura, Iwao Sekigawa
Background: MicroRNAs (miRNAs) are involved in the regulation of key biological processes and have been implicated in various diseases, including autoimmune disorders. The pathogenesis of polymyositis (PM) and dermatomyositis (DM) is considered to be mediated by autoimmune reactions. To determine miRNA role in the development and progression of PM and DM, we performed plasma miRNA profiling in PM/DM patients before and after treatment. Methods: Total RNA was isolated from plasma of 10 patients before and after treatment with prednisolone, or, in case of prednisolone resistance or complications, with the combination of calcineurin inhibitors (cyclosporine or tacrolims) and/or pulse intravenous cyclophosphamide...
2018: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29319621/selective-cd28-inhibition-modulates-alloimmunity-and-cardiac-allograft-vasculopathy-in-anti-cd154-treated-monkeys
#2
Tianshu Zhang, Agnes M Azimzadeh, Wenji Sun, Natalie A O'Neill, Evelyn Sievert, Emily Bergbower, Gheorghe Braileanu, Lars Burdorf, Xiangfei Cheng, Thomas Monahan, Siamak Dahi, Donald Harris, Elana Rybak, Emily Welty, Anthony Kronfli, Chris Avon, Richard N Pierson
BACKGROUND: Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade...
January 10, 2018: Transplantation
https://www.readbyqxmd.com/read/29318598/efficacy-and-safety-of-noncultured-melanocyte-keratinocyte-transplant-procedure-for-vitiligo-and-other-leukodermas-a-critical-analysis-of-the-evidence
#3
REVIEW
Paras P Vakharia, Dylan E Lee, Amor Khachemoune
Vitiligo is an acquired pigmentary skin of depigmentation occurring secondary to melanocyte destruction. Vitiligo and other leukodermas have a profound impact on quality of life. Current therapies include medical options, such as phototherapy, topical and systemic corticosteroids, topical calcineurin inhibitors, immunomodulators, and antioxidiants, and surgical options. Surgical options provide melanocytic cells to previously depigmented areas and use either tissue grafting or cellular grafting methods. Topical treatments are often insufficient, and many of the current surgical procedures have shown variable response rates...
January 10, 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/29314207/vitiligoid-variant-of-lichen-sclerosus-in-young-girls-with-darker-skin-types
#4
Margaret H Dennin, Sarah L Stein, Adena E Rosenblatt
BACKGROUND/OBJECTIVES: Vitiligo and lichen sclerosus are autoimmune disorders characterized by white discoloration, and both frequently affect the anogenital region. Vitiligoid lichen sclerosus refers to a superficial variant of lichen sclerosus in which the lesion appears clinically to be vitiligo based on the predominant presentation of depigmentation and minimal inflammation and sclerosis but histologically is consistent with lichen sclerosus. A limited number of reports have described vitiligoid lichen sclerosus, and from these reports, it appears to primarily affect darker-skinned people...
January 4, 2018: Pediatric Dermatology
https://www.readbyqxmd.com/read/29312858/de-novo-glomerular-diseases-after-renal-transplantation-how-is-it-different-from-recurrent-glomerular-diseases
#5
REVIEW
Fedaey Abbas, Mohsen El Kossi, Jon Kim Jin, Ajay Sharma, Ahmed Halawa
The glomerular diseases after renal transplantation can occur de novo, i.e., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original disease in the native kidney. There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease. However, structural alterations in transplanted kidney add to dilemma in diagnosis. These changes in architecture of histopathology can happen due to: (1) exposure to the immunosuppression specifically the calcineurin inhibitors (CNI); (2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cell-mediated immunological onslaught; (3) post-transplant viral infections; (4) ischemia-reperfusion injury; and (5) hyperfiltration injury...
December 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/29305867/binding-of-pick1-pdz-domain-with-calcineurin-b-regulates-osteoclast-differentiation
#6
Yuya Kamano, Jun Watanabe, Tsutomu Iida, Takeru Kondo, Hiroko Okawa, Hirofumi Yatani, Makio Saeki, Hiroshi Egusa
The calcineurin/nuclear factor of activated T cell (NFAT) signaling pathway plays a major role in osteoclast differentiation; however, the proteins that react with the calcineurin-NFAT complex in osteoclasts to regulate osteoclastogenesis remain unclear. Here, we present evidence that PICK1 also positively regulates calcineurin B in osteoclasts to activate NFAT to promote osteoclastogenesis. mRNA and protein expression of PICK1 in murine primary bone marrow macrophages (BMMs) was significantly increased during RANKL-induced osteoclast differentiation...
January 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29304536/defibrotide-stimulates-angiogenesis-and-protects-endothelial-cells-from-calcineurin-inhibitor-induced-apoptosis-via-upregulation-of-akt-bcl-xl
#7
Xiangmin Wang, Bin Pan, Yuko Hashimoto, Hiroshi Ohkawara, Kailin Xu, Lingyu Zeng, Takayuki Ikezoe
Sinusoidal obstruction syndrome is a life-threatening complication that can occur after haematopoietic stem cell transplantation. Defibrotide (DF) has been approved for the treatment of individuals with severe sinusoidal obstruction syndrome following haematopoietic stem cell transplantation in the European Union and the United States. However, the precise mechanisms by which DF protects endothelial cells remain to be elucidated. In this study, we found that DF stimulated angiogenesis in vitro and in vivo as assessed by vascular tube formation, scratch-wound repair and Matrigel plug assays...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29300232/early-postoperative-neutrophil-gelatinase-associated-lipocalin-predicts-the-development-of-chronic-kidney-disease-following-liver-transplantation
#8
Giuseppe Cullaro, Joseph F Pisa, Robert S Brown, Gebhard Wagener, Elizabeth C Verna
BACKGROUND: Urinary NGAL (uNGAL)-associated acute kidney injury (AKI) is common following liver transplant (LT), but whether early AKI predicts chronic kidney disease (CKD) and mortality remains uncertain. METHODS: Adults with LT from 2008-2010 in a previously published prospective cohort evaluating serial uNGAL pre- and post-LT were retrospectively assessed to evaluate uNGAL as a predictor of long-term outcomes post-LT. The primary outcomes were post-LT CKD, defined as MDRD estimated glomerular filtration rate (GFR)<60 mL/min/1...
January 3, 2018: Transplantation
https://www.readbyqxmd.com/read/29298826/granuloma-glutaeale-infantum-a-re-emerging-complication-of-diaper-dermatitis
#9
Rita Ramos Pinheiro, Eugénia Matos-Pires, Juliana Baptista, André Lencastre
Granuloma gluteale infantum is a rare nodular complication of irritant diaper dermatitis. The association of this condition with the widespread use of nondisposable cloth diapers has been increasingly recognized. We present the case of an 18-month-old girl with granuloma gluteale infantum. Our aims are to emphasize the importance of clinical recognition of this re-emerging complication of diaper dermatitis and to point out the potential role of topical calcineurin inhibitors as a treatment option.
January 3, 2018: Pediatrics
https://www.readbyqxmd.com/read/29298646/tacrolimus-pharmacokinetic-considerations-for-clinicians
#10
Katharina Schutte-Nutgen, Gerold Tholking, Barbara Suwelack, Stefan Reuter
The calcineurin inhibitor tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, clinical management of Tac therapy can be challenging because of its narrow therapeutic window and because many factors interfere with its metabolism. Therefore, therapeutic drug monitoring is used to adjust the dosage. Recently, we were able to classify patients receiving tacrolimus into two major metabolism groups by simple calculation of the C/D ratio (expressed as the blood concentration normalized by the dose)...
December 31, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29298401/penile-lichen-sclerosus-treated-with-1927%C3%A2-nm-thulium-fiber-laser-and-photodynamic-therapy-a-new-possible-therapeutic-approach
#11
Santo Raffaele Mercuri, Pina Brianti, Antonio Foti, Marco Bartolucci, Annunziata Dattola, Steven Paul Nisticò
OBJECTIVE: We treated two patients with recalcitrant lichen sclerosus (LS) of the penis with a combination of 1927 nm thulium fiber laser and methyl-aminolevulinate (MAL) photodynamic therapy (PDT). BACKGROUND DATA: Therapy of LS is based on topical potent steroids, emollients, and topical calcineurin inhibitors. Circumcision is effective, but not always accepted. PDT represents a valid therapeutic option in refractory cases, but there are no reports about the association with 1927 nm thulium laser in the treatment of this pathology...
January 3, 2018: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/29289721/spinal-sigma-1-receptor-mediated-dephosphorylation-of-astrocytic-aromatase-plays-a-key-role-in-formalin-induced-inflammatory-nociception
#12
Hoon-Seong Choi, Mi-Ji Lee, Sheu-Ran Choi, Branden A Smeester, Alvin J Beitz, Jang-Hern Lee
Aromatase is a key enzyme responsible for the biosynthesis of estrogen from testosterone. Although recent evidence indicates that spinal cord aromatase participates in nociceptive processing, the mechanisms underlying its regulation and its involvement in nociception remain unclear. The present study focuses on the potential role of astrocyte aromatase in formalin-induced acute pain and begins to uncover one mechanism by which spinal aromatase activation is controlled. Following intraplantar formalin injection, nociceptive responses were quantified and immunohistochemistry/co-immunoprecipitation assays were used to investigate the changes in spinal Fos expression and the phospho-serine levels of spinal aromatase...
December 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/29283464/tgf-%C3%AE-2-and-tgf-%C3%AE-3-from-cultured-%C3%AE-amyloid-treated-or-3xtg-ad-derived-astrocytes-may-mediate-astrocyte-neuronal-communication
#13
Laura Tapella, Matteo Cerruti, Isabella Biocotino, Alessio Stevano, Francesca Rocchio, Pier Luigi Canonico, Mariagrazia Grilli, Armando A Genazzani, Dmitry Lim
Astrocytes participate in the development and resolution of neuroinflammation in numerous ways, including the release of cytokines and growth factors. Among many, astrocytes release transforming growth factors beta (TGF-β) TGF-β1, TGF-β2 and TGF-β3. TGF-β1 is the most studied isoform, while production and release of TGF-β2 and 3 by astrocytes has been poorly characterized. Here we report that purified cultures of hippocampal astrocytes produce mainly TGF-β3 followed by TGF-β2 and TGF-β1. Furthermore, astrocytes release principally the active form of TGF-β3 over the other two...
December 28, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29274751/reduced-expression-of-na-ca2-exchangers-is-associated-with-cognitive-deficits-seen-in-alzheimer-s-disease-model-mice
#14
Shigeki Moriguchi, Satomi Kita, Masahiro Fukaya, Makoto Osanai, Ryo Inagaki, Yuzuru Sasaki, Hisanao Izumi, Kyoji Horie, Junji Takeda, Takashi Saito, Hiroyuki Sakagami, Takaomi C Saido, Takahiro Iwamoto, Kohji Fukunaga
Na+/Ca2+ exchangers (NCXs) are expressed primarily in the plasma membrane of most cell types, where they mediate electrogenic exchange of one Ca2+ for three Na+ ions, depending on Ca2+ and Na+ electrochemical gradients across the membrane. Three mammalian NCX isoforms (NCX1, NCX2, and NCX3) are each encoded by a distinct gene. Here, we report that NCX2 and NCX3 protein and mRNA levels are relatively reduced in hippocampal CA1 of APP23 and APP-KI mice. Likewise, NCX2+/- or NCX3+/- mice exhibited impaired hippocampal LTP and memory-related behaviors...
December 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29260318/the-utility-of-surveillance-biopsies-in-pediatric-kidney-transplantation
#15
Vikas R Dharnidharka, Neil Vyas, Joseph P Gaut, Leslie Walther, S Paul Hmiel
BACKGROUND: Surveillance biopsies (SBs) are performed in some pediatric kidney transplant programs, based on data obtained in earlier immunosuppressive eras that the treatment of subclinical acute rejection results in better graft survival. The benefit of SBs for patients on modern immunosuppression regimens is unclear. We have therefore evaluated the clinical utility of SBs in a population of children receiving a kidney transplant. METHODS: We have performed SBs at 3, 6 and 12 months post-transplantation as standard of care at our institution since 2013 in patients on a regimen of rabbit anti-thymocyte globulin, tacrolimus, mycophenolate and rapid steroid taper (RST; steroids maintained in some exceptions)...
December 19, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29258952/5-aminolevulinic-acid-photodynamic-therapy-in-refractory-vulvar-lichen-sclerosus-et-atrophicus-series-of-ten-cases
#16
Ting Lan, Yongzhen Zou, Michael R Hamblin, Rui Yin
BACKGROUND: Vulvar lichen sclerosus et atrophicus (VLSA) is a chronic inflammatory skin disease of unknown etiology that mainly affects postmenopausal and perimenopausal women. The primary clinical symptoms of VLSA are itching, burning pain, and dyspareunia that can results in decreased quality of life. Existing therapies including topical corticosteroid ointment, topical calcineurin inhibitors, estrogens, are not very effective for treatment of VLSA. OBJECTIVE: To evaluate the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) in the treatment of VLSA...
December 16, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29251576/pretransplant-hba1c-and-glucose-metabolism-parameters-in-predicting-posttransplant-diabetes-mellitus-and-their-course-in-the-first-6-months-after-living-donor-renal-transplant
#17
Namrata Rao, Manish Rathi, Ashish Sharma, Raja Ramachandran, Vivek Kumar, Harbir Singh Kohli, Krishan Lal Gupta, Vinay Sakhuja
OBJECTIVES: Posttransplant diabetes mellitus is a common and serious metabolic complication after renal transplant. Patients with uremia are known to have abnormal glucose metabolism characterized by insulin resistance and defects in insulin secretion, which are ameliorated to some extent with renal replacement therapy and more so with renal transplant. However, the diabetogenicity of calcineurin inhibitors compounds this state of dysglycemia and promotes the development of diabetes in some patients...
December 18, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29248522/phosphodiesterase-4-pde4-inhibitors
#18
Rema Zebda, Amy S Paller
Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy, with long term use, these agents have associated safety concerns and limitations. More targeted options with fewer systemic and cutaneous side effects are needed for treating atopic dermatitis. Phosphodiesterase 4 is involved in the regulation of proinflammatory cytokines via the degradation of cAMP...
December 14, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29236209/adverse-events-under-tacrolimus-and-cyclosporine-in-the-first-3-years-post-renal-transplantation-in-children
#19
Pauline Lancia, Beate Aurich, Phuong Ha, Anne Maisin, Véronique Baudouin, Evelyne Jacqz-Aigrain
BACKGROUND: Progress in immunosuppression has reduced acute rejection, graft loss and mortality after renal transplantation. Adverse drug reactions are well described in adults but few data are available in children. Our objectives were to analyse the adverse events reported in the first 3 years post-transplantation in children receiving tacrolimus or cyclosporine-based immunosuppression and compare them with the information of the Summary of Product Characteristics. METHODS: This retrospective study included all children who underwent a renal transplant at Hospital Robert Debré between 2002 and 2015...
December 13, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29226570/campath-calcineurin-inhibitor-reduction-and-chronic-allograft-nephropathy-the-3c-study-results-of-a-randomized-controlled-clinical-trial
#20
Richard Haynes, Lisa Blackwell, Natalie Staplin, William G Herrington, Jonathan Emberson, Parminder K Judge, Benjamin C Storey, Martin J Landray, Paul N Harden, Colin Baigent, Peter Friend
Calcineurin inhibitors (CNI e.g. tacrolimus) reduce short-term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin pathway (mTOR e.g. sirolimus) might avoid long-term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial comprising sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6-months post-transplant...
December 11, 2017: American Journal of Transplantation
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