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https://www.readbyqxmd.com/read/28230738/clinical-implications-of-20-hydroxyeicosatetraenoic-acid-in-the-kidney-liver-lung-and-brain-an-emerging-therapeutic-target
#1
REVIEW
Osama H Elshenawy, Sherif M Shoieb, Anwar Mohamed, Ayman O S El-Kadi
Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport...
February 20, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28230617/acute-kidney-injury-following-efavirenz-tenofovir-disoproxil-fumarate-emtricitabine-atripla%C3%A2-overdose
#2
Thomas Havenith, David Burger, Maarten Visschers, Jolanda Schippers, Astrid Oude Lashof
We describe a patient with acute renal failure and irreversible kidney damage after an overdose with the fixed dose combination of efavirenz/tenofovir disoproxil fumarate/emtricitabine (Atripla). The acute kidney injury was most probably caused by tenofovir. Efavirenz and emtricitabine seemed relatively safe in overdose. The pharmacokinetics in overdose of all three drugs and the effect of hemodialysis on the tenofovir clearance were studied by measuring the plasma concentrations and by the use of clinical pharmacokinetic software...
February 20, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28230232/carisbamate-blockade-of-t-type-voltage-gated-calcium-channels
#3
Do Young Kim, Fang-Xiong Zhang, Stan T Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G Sullivan, S R Wayne Chen, Gerald W Zamponi, Jong M Rho
OBJECTIVES: Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca(2+) ]i . METHODS: We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload-Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca(2+) ]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T-type voltage-gated Ca(2+) channels...
February 23, 2017: Epilepsia
https://www.readbyqxmd.com/read/28230089/endothelin-receptor-specific-control-of-endoplasmic-reticulum-stress-and-apoptosis-in-the-kidney
#4
Carmen De Miguel, William C Hamrick, Janet L Hobbs, David M Pollock, Pamela K Carmines, Jennifer S Pollock
Endothelin-1 (ET-1) promotes renal damage during cardiovascular disease; yet, the molecular mechanisms involved remain unknown. Endoplasmic reticulum (ER) stress, triggered by unfolded protein accumulation in the ER, contributes to apoptosis and organ injury. These studies aimed to determine whether the ET-1 system promotes renal ER stress development in response to tunicamycin. ETB deficient (ETB def) or transgenic control (TG-con) rats were used in the presence or absence of ETA receptor antagonism. Tunicamycin treatment similarly increased cortical ER stress markers in both rat genotypes; however, only ETB def rats showed a 14-24 fold increase from baseline for medullary GRP78, sXBP-1, and CHOP...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229293/age-related-hearing-loss-and-dementia-a-10-year-national-population-based-study
#5
Peijen Su, Chih-Chao Hsu, Hung-Ching Lin, Wei-Shin Huang, Tsung-Lin Yang, Wei-Ting Hsu, Cheng-Li Lin, Chung-Yi Hsu, Kuang-Hsi Chang, Yi-Chao Hsu
Age-related hearing loss (ARHL) is postulated to affect dementia. Our study aims to investigate the relationship between ARHL and the prevalence, and 10-year incidence of dementia in the Taiwan National Health Insurance Research Database (NHIRD). We selected patients diagnosed with ARHL from the NHIRD. A comparison cohort comprising of patients without ARHL was frequency-matched by age, sex, and co-morbidities, and the occurrence of dementia was evaluated in both cohorts. The ARHL cohort consisted of 4108 patients with ARHL and the control cohort consisted of 4013 frequency-matched patients without ARHL...
February 22, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28229281/cell-therapeutic-approaches-to-immunosuppression-after-clinical-kidney-transplantation
#6
REVIEW
Christian Morath, Anita Schmitt, Florian Kälble, Martin Zeier, Michael Schmitt, Flavius Sandra-Petrescu, Gerhard Opelz, Peter Terness, Matthias Schaier, Christian Kleist
Refinement of immunosuppressive strategies has led to further improvement of kidney graft survival in recent years. Currently, the main limitations to long-term graft survival are life-threatening side effects of immunosuppression and chronic allograft injury, emphasizing the need for innovative immunosuppressive regimens that resolve this therapeutic dilemma. Several cell therapeutic approaches to immunosuppression and donor-specific unresponsiveness have been tested in early phase I and phase II clinical trials in kidney transplantation...
February 23, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28229254/the-impact-of-post-procedural-complications-on-reimbursement-length-of-stay-and-mechanical-ventilation-among-patients-undergoing-transcatheter-aortic-valve-implantation-in-germany
#7
Klaus Kaier, Holger Reinecke, Huseyin Naci, Lutz Frankenstein, Martin Bode, Werner Vach, Philip Hehn, Andreas Zirlik, Manfred Zehender, Jochen Reinöhl
BACKGROUND: The impact of various post-procedural complications after transcatheter aortic valve implantation (TAVI) on resource use and their consequences in the German reimbursement system has still not been properly quantified. METHODS: In a retrospective observational study, we use data from the German DRG statistic on patient characteristics and in-hospital outcomes of all isolated TAVI procedures in 2013 (N = 9147). The impact of post-procedural complications on reimbursement, length of stay and mechanical ventilation was analyzed using both unadjusted and risk-adjusted linear and logistic regression analyses...
February 22, 2017: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
https://www.readbyqxmd.com/read/28229039/clofarabine-desensitization-a-case-report-leukemia-research-reports
#8
Sarah M Hayes, Justin A Wasko, Erica Dahl Warlick
We describe a relapsed AML patient who had two prior severe reactions to clofarabine involving rigors, emesis, tachycardia, hypotension, and acute kidney injury. Given previous prolonged remission achieved with clofarabine and cytarabine therapy years prior, rechallenge was undertaken upon discovery of AML relapse. We designed a desensitization protocol performed with the first dose of clofarabine, leading to successful administration of the entire clofarabine/cytarabine treatment course. From this case we show promise for clofarabine rechallenge after prior hypersensitivity reactions in patients with few treatment options for relapsed AML...
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28228406/renal-inflammation-and-injury-is-associated-with-lymphangiogenesis-in-hypertension
#9
Sterling C Kneedler, Lauren E Phillips, Kayla R Hudson, Katharine M Beckman, Catalina A Lopez Gelston, Joseph M Rutkowski, Alan R Parrish, Peter A Doris, Brett M Mitchell
Lymphatic vessels are vital for the trafficking of immune cells from the interstitium to draining lymph nodes during inflammation. Hypertension is associated with renal infiltration of activated immune cells and inflammation, however it is unknown how renal lymphatic vessels change in hypertension. We hypothesized that renal macrophage infiltration and inflammation would cause increased lymphatic vessel density in hypertensive rats. Spontaneously hypertensive rats (SHR) that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased renal lymphatic vessel density and macrophages at 40 weeks of age compared to Wistar-Kyoto (WKY) controls...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28228404/endothelial-colony-forming-cells-ameliorate-endothelial-dysfunction-via-secreted-factors-following-ischemia-reperfusion-injury
#10
Jason A Collett, Purvi Mehrotra, Allison Crone, W Christopher Shelley, Mervin C Yoder, David P Basile
Damage to endothelial cells contributes to acute kidney injury (AKI) by leading to impaired perfusion. Endothelial colony-forming cells (ECFCs) are endothelial precursor cells with high proliferative capacity, pro-angiogenic activity, and in vivo vessel forming potential. We hypothesized that ECFCs may ameliorate the degree of AKI and/or promote repair of the renal vasculature following ischemia/reperfusion (I/R). Rat pulmonary microvascular ECs (PMVEC) with high proliferative potential were compared with pulmonary artery ECs (PAEC) with low proliferative potential in rats subjected to renal I/R...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28226413/thrombalexin-use-of-a-cytotopic-anticoagulant-to-reduce-thrombotic-microangiopathy-in-a-highly-sensitized-model-of-kidney-transplantation
#11
Miriam Manook, Jean Kwun, Christian Burghuber, Kannan Samy, Michael Mulvihill, Janghoon Yoon, He Xu, Andrea L MacDonald, Kyle Freischlag, Verna Curfman, Evelyn Branum, David Howell, Alton Brad Farris, Richard A Smith, Stephen Sacks, Anthony Dorling, Nizam Mamode, Stuart Knechtle
Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anti-coagulation is difficult due to bleeding. A novel 'cytotopic' agent, 'Thrombalexin', (TLN) combines a cell-membrane bound (mirystoyl tail) anti-thrombin (HLL peptide) which can be perfused directly to the donor organ or cells.. Thromboelastography (TEG) was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN vs...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28226404/the-effect-of-cortex-medulla-proportions-on-molecular-diagnoses-in-kidney-transplant-biopsies-rejection-and-injury-can-be-assessed-in-medulla
#12
Katelynn S Madill-Thomsen, Roger C Wiggins, Farsad Eskandary, Georg A Böhmig, Philip F Halloran
Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes e...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28225877/synthetic-cannabinoids-in-the-kidneys
#13
Alper Alp, Hakan Akdam, Banu Yılmaz Avcıoğlu, Sibel Ersan
Acute kidney injury is an important cause of mortality and morbidity today and can occur due to several reasons. As time, geographic regions, and living conditions change, various etiological agents arise with nephrotoxic effects. Awareness of such nephrotoxic effects has been raised with the increasing frequency of addictive substance use, especially among young people in society.
January 1, 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28225865/continuous-blood-purification-treatment-for-endotoxin-induced-acute-respiratory-distress-syndrome
#14
Y Jiang, R Lin, Y Xu, S Zhang, K Cui, M Zhu, A Li, C Chen, J Yang, W Yang
This study aimed to explore the effects of continuous blood purification (CBP) treatment in pigs affected with acute respiratory distress syndrome (ARDS). A total of 12 healthy male pigs, weighing 12±1.8 kg, were randomly and equally assigned to the control and experimental groups. The ARDS pig model was prepared by intravenous injections of endotoxin (20 µg/kg). The control group was given conventional supportive therapy, while the experimental group was given continuous veno-venous hemofiltration therapy...
February 16, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28225832/elevated-bilirubin-levels-are-associated-with-a-better-renal-prognosis-and-ameliorate-kidney-fibrosis
#15
Sehoon Park, Do Hyoung Kim, Jin Ho Hwang, Yong-Chul Kim, Jin Hyuk Kim, Chun Soo Lim, Yon Su Kim, Seung Hee Yang, Jung Pyo Lee
BACKGROUND: Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. METHODS: We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis...
2017: PloS One
https://www.readbyqxmd.com/read/28225801/perioperative-hemoglobin-area-under-the-curve-is-an-independent-predictor-of-renal-failure-after-cardiac-surgery-results-from-a-spanish-multicenter-retrospective-cohort-study
#16
Paula Duque-Sosa, Diego Martínez-Urbistondo, Gemma Echarri, Raquel Callejas, María Josefa Iribarren, Gregorio Rábago, Pablo Monedero
Perioperative anemia is an important risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). Nonetheless, the severity of the anemia and the time in the perioperative period in which the hemoglobin level should be considered as a risk factor is conflicting. The present study introduces the concept of perioperative hemoglobin area under the curve (pHb-AUC) as a surrogate marker of the evolution of perioperative hemoglobin concentration. Through a retrospective analysis of prospectively collected data, we assessed this new variable as a risk factor for the development of acute kidney injury after cardiac surgery in 966 adult patients who underwent cardiac surgery with cardiopulmonary bypass, at twenty-three academic hospitals in Spain...
2017: PloS One
https://www.readbyqxmd.com/read/28224940/telemedicine-to-promote-patient-safety-use-of-phone-based-interactive-voice-response-system-to-reduce-adverse-safety-events-in-pre-dialysis-ckd
#17
REVIEW
Shoshana Weiner, Jeffery C Fink
CKD patients have several features conferring on them a high risk of adverse safety events, which are defined as incidents with unintended harm related to processes of care or medications. These characteristics include impaired kidney function, polypharmacy, and frequent health system encounters. The consequences of such events in CKD can include new or prolonged hospitalization, accelerated kidney function loss, acute kidney injury, ESRD, and death. Health information technology administered via telemedicine presents opportunities for CKD patients to remotely communicate safety-related findings to providers for the purpose of improving their care...
January 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28224231/nc-6004-phase-i-study-in-combination-with-gemcitabine-for-advanced-solid-tumors-and-population-pk-pd-analysis
#18
Toshihiko Doi, Tetsuya Hamaguchi, Kohei Shitara, Satoru Iwasa, Yasuhiro Shimada, Mitsunori Harada, Kenichiro Naito, Naoto Hayashi, Atsuhiro Masada, Atsushi Ohtsu
OBJECTIVES: This study was an open-label phase I study to confirm the safety and tolerability of NC-6004 in combination with gemcitabine in Japanese patients with advanced solid tumors and to assess the PK effects of NC-6004 monotherapy. METHODS: This phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) and recommended dose of NC-6004 combined with gemcitabine. Safety and pharmacokinetics were assessed. The administration of NC-6004 alone was started at 60 mg/m(2) every treatment cycle (21 days per cycle)...
February 21, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28224201/dexmedetomidine-protects-against-cisplatin-induced-acute-kidney-injury-in-mice-through-regulating-apoptosis-and-inflammation
#19
H Liang, H-Z Liu, H-B Wang, J-Y Zhong, C-X Yang, B Zhang
OBJECTIVE AND DESIGN: Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury. MATERIALS: Acute kidney injury in mice was induced by cisplatin. TREATMENTS: Mice were administered with DEX 25 μg/kg or atipamezole 250 μg/kg (once a day, for 3 days) after cisplatin treatment...
February 21, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28223138/foxc1-and-foxc2-are-necessary-to-maintain-glomerular-podocytes
#20
Masaru Motojima, Tsutomu Kume, Taiji Matsusaka
Foxc1 and Foxc2 (Foxc1/2) are transcription factors involved in many biological processes. In adult kidneys, expression of Foxc1/2 is confined to the glomerular epithelial cells, i.e., podocytes. To bypass embryonic lethality of Foxc1/2 null mice, mice ubiquitously expressing inducible-Cre (ROSA26-CreER(T2)) or mice expressing Cre in podocytes (Nephrin-Cre) were mated with floxed-Foxc1 and floxed-Foxc2 mice. The CreER(T2) was activated in adult mice by administrations of tamoxifen. Eight weeks after tamoxifen treatment, ROSA26-CreER(T2); Foxc1(+/flox); Foxc2(flox/flox) mice developed microalbuminuria, while ROSA26-Cre ER(T2); Foxc1(flox/flox); Foxc2(+/flox) mice had no microalbuminuria...
February 18, 2017: Experimental Cell Research
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