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https://www.readbyqxmd.com/read/29667225/activation-of-central-gaba-b-receptors-offsets-the-cyclosporine-counteraction-of-endotoxic-cardiovascular-outcomes-in-conscious-rats
#1
Marwa Y Sallam, Sahar M El-Gowilly, Abdel-Galil A Abdel-Galil, Mahmoud M El-Mas
We have previously shown that cyclosporine (CSA) counteracts cardiovascular manifestations induced by endotoxemia (lipopolysaccharide, LPS) such as hypotension and cardiac autonomic dysfunction in conscious rats. In this study we investigated whether the facilitation of central γ-amino butyric acid (GABA) neurotransmission blunts these favorable influences of CSA. The LPS-CSA interaction was determined in the absence and presence of drugs that activate GABAA or GABAB receptors or elevate synaptic GABA levels in the central nervous system...
April 18, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29666154/prediction-and-quantification-of-hepatic-transporter-mediated-uptake-of-pitavastatin-utilizing-a-combination-of-the-relative-activity-factor-approach-and-mechanistic-modeling
#2
Pallabi Mitra, Samantha Weinheimer, Meeghan Michalewicz, Mitchell E Taub
Quantification of the fraction transported (ft) by a particular transporter will facilitate more robust estimations of transporter interactions. Using pitavastatin as a model uptake transporter substrate, we investigated the utility of the relative activity factor (RAF) approach and mechanistic modeling, to estimate ft in hepatocytes. Transporters evaluated were OATP1B1, OATP1B3, and NTCP. Transporter expressing HEK293 cells and human hepatocytes were used for determining RAF values, which were then incorporated into the mechanistic model to simulate hepatocyte uptake of pitavastatin over time...
April 17, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29666121/clinical-features-and-visual-outcomes-of-111-patients-with-new-onset-acute-vogt-koyanagi-harada-disease-treated-with-pulse-intravenous-corticosteroids
#3
Makiko Nakayama, Hiroshi Keino, Takayo Watanabe, Annabelle A Okada
PURPOSE: To describe the clinical features, treatment and visual outcomes of Japanese patients with new-onset acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Clinical records of 111 patients who presented between 1999 and 2015 to the Ocular Inflammation Service of the Kyorin Eye Center, Tokyo, were reviewed. RESULTS: Of the 111 patients (68 women, 43 men), 16 had complete, 90 had incomplete and 5 had probable VKH disease. The median follow-up period was 36 months (4-175 months)...
April 17, 2018: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/29665840/effects-of-cyclosporine-a-pretreatment-of-deceased-organ-donors-on-kidney-graft-function-cis-a-rein-study-protocol-for-a-randomized-controlled-trial
#4
Jean-Christophe Orban, Eric Fontaine, Elisabeth Cassuto, Karine Baumstarck, Marc Leone, Jean-Michel Constantin, Carole Ichai
BACKGROUND: Renal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF...
April 17, 2018: Trials
https://www.readbyqxmd.com/read/29663071/cyclosporine-a-responsive-congenital-nephrotic-syndrome-with-single-heterozygous-variants-in-nphs1-nphs2-and-plce1
#5
Anna Eichinger, Sabine Ponsel, Carsten Bergmann, Roman Günthner, Julia Hoefele, Kerstin Amann, Bärbel Lange-Sperandio
BACKGROUND: Congenital nephrotic syndrome (CNS) is primarily a monogenetic disease, with the majority of cases due to changes in five different genes: the nephrin (NPHS1), podocin (NPHS2), Wilms tumor 1 (WT1), laminin ß2 (LAMB2), and phospholipase C epsilon 1 (PLCE1, NPHS3) gene. Usually CNS is not responsive to immunosuppressive therapy, but treatment with ACE inhibitors, AT1 receptor blockade and/or indomethacin can reduce proteinuria. If the disease progresses to end-stage renal disease, kidney transplantation is the therapy of choice...
April 16, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29661840/therapeutic-potential-of-a-novel-necrosis-inhibitor-7-amino-indole-in-myocardial-ischemia-reperfusion-injury
#6
In-Chang Hwang, Ju-Young Kim, Ji-Hyun Kim, Joo-Eun Lee, Ji-Yun Seo, Jae-Won Lee, Jonghanne Park, Han-Mo Yang, Soon-Ha Kim, Hyun-Jai Cho, Hyo-Soo Kim
Opening of mitochondrial permeability transition pore and Ca2+ overload are main contributors to myocardial ischemia-reperfusion injury, which paradoxically causes a wide variety of myocardial damage. We investigated the protective role of a novel necrosis inhibitor (NecroX-7; NecX) against myocardial ischemia-reperfusion injury using in vitro and in vivo models. H9C2 rat cardiomyoblasts and neonatal cardiomyocytes were exposed to hypoxia-reoxygenation stress after pre-treatment with NecX, vitamin C, a combination of vitamin C and E, N-acetylcysteine, an apoptosis inhibitor (Z-VAD-fmk), or cyclosporine A...
April 16, 2018: Hypertension
https://www.readbyqxmd.com/read/29661467/paradoxical-reaction-of-tuberculosis-in-a-heart-transplant-recipient-during-antituberculosis-therapy-a-case-report
#7
A Wakamiya, O Seguchi, A Shionoiri, Y Kumai, K Kuroda, S Nakajima, M Yanase, S Matsuda, K Wada, Y Matsumoto, S Fukushima, T Fujita, J Kobayashi, N Fukushima
INTRODUCTION: Tuberculous paradoxical reactions (PRs) are excessive immune reactions occurring after antituberculosis (TB) treatment and are commonly observed in immunocompromised hosts such as patients infected with the human immunodeficiency virus. CASE REPORT: We recently encountered a 63-year-old male heart transplant recipient who developed tuberculous PR after treatment for miliary TB. The patient had been receiving immunosuppressive therapy with cyclosporine and mycophenolate mofetil for over 15 years...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29661458/ombitasvir-paritaprevir-ritonavir-therapy-in-a-kidney-transplant-recipient-with-chronic-hepatitis-c-virus-genotype-1-infection-a-case-report-on-the-importance-of-considering-drug-drug-interactions-and-monitoring-cyclosporine-levels
#8
S Takeuchi, M Takamura, T Yoshida, K Takahashi, K Hayashi, S Hashimoto, S Yamagiwa, M Tasaki, Y Nakagawa, K Saito, Y Tanabe, Y Tomita, S Terai
A 74-year-old Japanese man with a history of chronic hepatitis C and kidney transplant (KT) was administered pegylated-interferon plus ribavirin therapy. However, this therapy was ineffective. The patient was then hospitalized to receive ombitasvir (OBV) plus paritaprevir (PTV) plus ritonavir (r) antiviral combination therapy. He tested negative for the virus after 4 weeks, and completed 12 weeks of treatment. The patient ultimately achieved a sustained virological response after the 12 weeks of treatment. Cyclosporine (CyA) trough levels, during the OBV-PTV-r therapy, reached a peak within 5 days of initiating therapy, and increases in serum creatinine and total bilirubin were also observed...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29661453/late-onset-post-transplantation-central-nervous-system-lymphoproliferative-disorder-case-report
#9
J Rego Silva, R A Macau, H Oliveira Coelho, F Camelo, P Cruz, A Mateus, A Oliveira, C Oliveira, A Ramos
Post-transplantation lymphoproliferative disorder (PTLD) is a heterogeneous group of conditions that complicate organ transplantation and are due to immunosuppression. Central nervous system (CNS)-PTLD is rare but its incidence is increasing. It often occurs late and is associated with kidney transplantation and Epstein-Barr virus (EBV) infection. Outcomes are poor. We present the case of a 77-year-old white male who received a cadaveric kidney transplant in 2003. Maintenance immunosuppression consisted of mycofenolate mofetil (MMF), cyclosporine, and prednisolone...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29661443/cyclosporine-versus-tacrolimus-which-calcineurin-inhibitor-has-influence-on-cytomegalovirus-infection-in-cardiac-transplantation
#10
Marina M K Bond, Marisa M K Bond, A Sehn, V H Dias, T L Said, C C Dos Santos, M A Finger, A M G Santos, J M R Neto
INTRODUCTION: Cytomegalovirus (CMV) infection is a relevant cause of morbidity and mortality in transplantation patients. Its major incidence is in the first year and viral replication is related to acute rejection, survival reduction, and graft vascular disease. OBJECTIVE: This study aims to evaluate retrospectively whether a high dose of calcineurin inhibitors correlates with CMV-positive polymerase chain reaction (PCR), need for treatment, and death in cardiac transplantation patients...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29661427/hepatitis-c-virus-eradication-in-kidney-transplant-recipients-a-single-center-experience-in-portugal
#11
A Weigert, S Querido, L Carvalho, L Lebre, C Chagas, P Matias, R Birne, C Nascimento, C Jorge, T Adragão, M Bruges, D Machado
INTRODUCTION: Hepatitis C (HCV) is a major cause of liver impairment post-kidney transplantation (KT). Anti-HCV direct-acting antivirals (DAA) made viral eradication possible. METHODS: We performed a retrospective review of KT patients (n = 23) who received DAA at our hospital. Sustained viral response (SVR) was defined as absence of viral detection 12 weeks after cessation of therapy. RESULTS: From 1985 to September 2017, 1440 patients underwent transplantation at Hospital Santa Cruz...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29658384/complications-of-adult-onset-still-s-disease-and-their-management
#12
Stéphane Mitrovic, Bruno Fautrel
Adult-onset Still's disease (AOSD) is a rare systemic auto-inflammatory disorder in which management and treatment have considerably progressed over the past decade. Despite wide use of interleukin (IL)-1 or IL-6 inhibitors, serious complications remain possible. Areas covered: A comprehensive literature search in MEDLINE via Pubmed was performed to review AOSD's severe and sometimes life-threatening complications: reactive hemophagocytic lymphohystiocytosis, coagulation disorders, fulminant hepatitis, cardiac or pulmonary complications and amyloid A amyloidosis...
April 16, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29657214/kaposi-s-sarcoma-in-patients-with-membranous-nephropathy
#13
Weihua Liu, Feiyue Lin, Xin Chen, Lixin Wei, Jiabin Wu
Although the relationship between Kaposi's sarcoma (KS) and renal transplant has been well described, there are rare cases of KS concurrent with membranous glomerulonephritis or other glomerular diseases. In this report, a patient with membranous glomerulonephritis that accepted long-term prednisolone and cyclosporine immunosuppressive therapy developed skin KS. Withdrawal of immunosuppressive treatment resulted in the disappearance of KS.
March 2018: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/29651627/equivalence-testing-of-complex-particle-size-distribution-profiles-based-on-earth-mover-s-distance
#14
Meng Hu, Xiaohui Jiang, Mohammad Absar, Stephanie Choi, Darby Kozak, Meiyu Shen, Yu-Ting Weng, Liang Zhao, Robert Lionberger
Particle size distribution (PSD) is an important property of particulates in drug products. In the evaluation of generic drug products formulated as suspensions, emulsions, and liposomes, the PSD comparisons between a test product and the branded product can provide useful information regarding in vitro and in vivo performance. Historically, the FDA has recommended the population bioequivalence (PBE) statistical approach to compare the PSD descriptors D50 and SPAN from test and reference products to support product equivalence...
April 12, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29651464/hex-a-heterologous-expression-platform-for-the-discovery-of-fungal-natural-products
#15
Colin J B Harvey, Mancheng Tang, Ulrich Schlecht, Joe Horecka, Curt R Fischer, Hsiao-Ching Lin, Jian Li, Brian Naughton, James Cherry, Molly Miranda, Yong Fuga Li, Angela M Chu, James R Hennessy, Gergana A Vandova, Diane Inglis, Raeka S Aiyar, Lars M Steinmetz, Ronald W Davis, Marnix H Medema, Elizabeth Sattely, Chaitan Khosla, Robert P St Onge, Yi Tang, Maureen E Hillenmeyer
For decades, fungi have been a source of U.S. Food and Drug Administration-approved natural products such as penicillin, cyclosporine, and the statins. Recent breakthroughs in DNA sequencing suggest that millions of fungal species exist on Earth, with each genome encoding pathways capable of generating as many as dozens of natural products. However, the majority of encoded molecules are difficult or impossible to access because the organisms are uncultivable or the genes are transcriptionally silent. To overcome this bottleneck in natural product discovery, we developed the HEx (Heterologous EXpression) synthetic biology platform for rapid, scalable expression of fungal biosynthetic genes and their encoded metabolites in Saccharomyces cerevisiae ...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29648675/clinical-features-of-chronic-spontaneous-urticaria-that-predict-disease-prognosis-and-refractoriness-to-standard-treatment
#16
Laia Curto-Barredo, Laura Riba Archilla, Guillem Roura Vives, Ramon M Pujol, Ana M Giménez-Arnau
Chronic spontaneous urticaria (CSU) is characterized by heterogeneous activity, evolution, associated comorbidities and response to treatment. The aim of this study was to identify prognostic factors in patients with CSU that predict disease course and response to standard treatments. An observational retrospective study was conducted in a cohort of 549 patients with CSU, comparing patients with isolated CSU and those with CSU with concomitant inducible urticaria (CSU-CIndU). The factors associated with a worse prognosis in terms of duration and/or CSU activity and its episodes were: multiple episodes of CSU (19...
April 12, 2018: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29648533/the-effect-of-fluconazole-on-the-pharmacokinetics-of-everolimus-and-tacrolimus-in-a-heart-transplant-recipient-a-case-report
#17
Kazuki Nakagita, Kyoichi Wada, Yuka Terada, Sachi Matsuda, Nobue Terakawa, Akira Oita, Mitsutaka Takada
OBJECTIVE: Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been used in combination with calcineurin inhibitors (tacrolimus and cyclosporine) to prevent allograft rejection following organ transplantation. In heart transplant recipients, everolimus should be maintained at a target blood concentration of 3 - 8 ng/mL, in combination with reduced-dose calcineurin inhibitors and therefore, requires strict monitoring. Fluconazole, an azole antifungal agent, affects blood concentration of tacrolimus by inhibiting the cytochromes P450 (CYP) 3A4 and 3A5...
April 12, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29644247/quantification-of-torque-teno-virus-and-epstein-barr-virus-is-of-limited-value-for-predicting-the-net-state-of-immunosuppression-after-lung-transplantation
#18
Rickard Nordén, Jesper Magnusson, Anna Lundin, Ka-Wei Tang, Staffan Nilsson, Magnus Lindh, Lars-Magnus Andersson, Gerdt C Riise, Johan Westin
Background: Major hurdles for survival after lung transplantation are rejections and infectious complications. Adequate methods for monitoring immune suppression status are lacking. Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. Methods: This prospective single-center study included 98 patients followed for 2 years after transplantation...
April 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29644081/risk-of-adverse-events-from-different-drugs-for-sle-a-systematic-review-and-network-meta-analysis
#19
Jingru Tian, Yien Luo, Haijing Wu, Hai Long, Ming Zhao, Qianjin Lu
Objective: The comparative safety of immunosuppressive drugs, biologicals and glucocorticoids (GC) for patients with SLE remains controversial. We aimed to investigate the specific side effects of the available SLE drugs in this population of patients. Methods: Electronic databases were systematically searched through September 2017 for randomised trials in patients with SLE. The primary outcomes were all-cause mortality and withdrawal related to adverse events (AEs)...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29643244/sun1-regulates-hiv-1-nuclear-import-in-a-manner-dependent-on-the-interaction-between-the-viral-capsid-and-cellular-cyclophilin-a
#20
Xinlong Luo, Wei Yang, Guangxia Gao
HIV-1 can infect non-dividing cells via passing through the nuclear pore complex. The nuclear membrane imbedded protein SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether SUN1, which shares many functional similarities with SUN2, is involved in this process remained to be explored. Here, we report that overexpression of SUN1 specifically inhibited the infection of HIV-1, but not simian immunodeficiency virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect reverse transcription, but led to reduced accumulation of the 2-LTR circular DNA and integrated viral DNA, suggesting a block in the process of nuclear import...
April 11, 2018: Journal of Virology
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