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https://www.readbyqxmd.com/read/29445145/canagliflozin-mediated-dual-inhibition-of-mitochondrial-glutamate-dehydrogenase-and-complex-i-an-off-target-adverse-effect
#1
Philipp F Secker, Sascha Beneke, Nadja Schlichenmaier, Johannes Delp, Simon Gutbier, Marcel Leist, Daniel R Dietrich
Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29434652/the-open-abdomen-in-trauma-and-non-trauma-patients-wses-guidelines
#2
REVIEW
Federico Coccolini, Derek Roberts, Luca Ansaloni, Rao Ivatury, Emiliano Gamberini, Yoram Kluger, Ernest E Moore, Raul Coimbra, Andrew W Kirkpatrick, Bruno M Pereira, Giulia Montori, Marco Ceresoli, Fikri M Abu-Zidan, Massimo Sartelli, George Velmahos, Gustavo Pereira Fraga, Ari Leppaniemi, Matti Tolonen, Joseph Galante, Tarek Razek, Ron Maier, Miklosh Bala, Boris Sakakushev, Vladimir Khokha, Manu Malbrain, Vanni Agnoletti, Andrew Peitzman, Zaza Demetrashvili, Michael Sugrue, Salomone Di Saverio, Ingo Martzi, Kjetil Soreide, Walter Biffl, Paula Ferrada, Neil Parry, Philippe Montravers, Rita Maria Melotti, Francesco Salvetti, Tino M Valetti, Thomas Scalea, Osvaldo Chiara, Stefania Cimbanassi, Jeffry L Kashuk, Martha Larrea, Juan Alberto Martinez Hernandez, Heng-Fu Lin, Mircea Chirica, Catherine Arvieux, Camilla Bing, Tal Horer, Belinda De Simone, Peter Masiakos, Viktor Reva, Nicola DeAngelis, Kaoru Kike, Zsolt J Balogh, Paola Fugazzola, Matteo Tomasoni, Rifat Latifi, Noel Naidoo, Dieter Weber, Lauri Handolin, Kenji Inaba, Andreas Hecker, Yuan Kuo-Ching, Carlos A Ordoñez, Sandro Rizoli, Carlos Augusto Gomes, Marc De Moya, Imtiaz Wani, Alain Chichom Mefire, Ken Boffard, Lena Napolitano, Fausto Catena
Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartment syndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangements and multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinical situations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source of infection or the necessity to re-explore (as a "planned second-look" laparotomy) or complete previously initiated damage control procedures or in cases of abdominal wall disruption...
2018: World Journal of Emergency Surgery: WJES
https://www.readbyqxmd.com/read/29429824/the-polyploid-state-plays-a-tumor-suppressive-role-in-the-liver
#3
Shuyuan Zhang, Kejin Zhou, Xin Luo, Lin Li, Ho-Chou Tu, Alfica Sehgal, Liem H Nguyen, Yu Zhang, Purva Gopal, Branden D Tarlow, Daniel J Siegwart, Hao Zhu
Most cells in the liver are polyploid, but the functional role of polyploidy is unknown. Polyploidization occurs through cytokinesis failure and endoreduplication around the time of weaning. To interrogate polyploidy while avoiding irreversible manipulations of essential cell-cycle genes, we developed orthogonal mouse models to transiently and potently alter liver ploidy. Premature weaning, as well as knockdown of E2f8 or Anln, allowed us to toggle between diploid and polyploid states. While there was no detectable impact of ploidy alterations on liver function, metabolism, or regeneration, mice with more polyploid hepatocytes suppressed tumorigenesis and mice with more diploid hepatocytes accelerated tumorigenesis in mutagen- and high-fat-induced models...
February 5, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29425319/changes-in-temporary-disability-reporting-following-the-implementation-of-the-army-medical-readiness-transformation
#4
Jason E Sapp, Matthew J Cody, Kevin M Douglas
Introduction: In November 2014, the U.S. Army held a readiness summit to address concerns about the accuracy of medical reporting systems. At the time, soldiers on temporary disability were tracked as a medical readiness classification (MRC) 3A or 3B. MRC 3A soldiers had a medical condition with recovery expected within 30 d and MRC 3B soldiers were expected to take longer than 30 d to recover. Both groups were considered "non-available" and presumably non-deployable. Starting June 1, 2016, with the implementation of the Army Medical Readiness Transformation, soldiers on temporary disability longer than 14 d began to be reported as MRC 3s and are considered "non-deployable...
February 7, 2018: Military Medicine
https://www.readbyqxmd.com/read/29396029/prenatal-treatment-of-ornithine-transcarbamylase-deficiency
#5
Yael Wilnai, Yair J Blumenfeld, Kristina Cusmano, Susan R Hintz, Deborah Alcorn, William E Benitz, William E Berquist, Jonathan A Bernstein, Ricardo O Castillo, Waldo Concepcion, Tina M Cowan, Kenneth L Cox, Deirdre J Lyell, Carlos O Esquivel, Margaret Homeyer, Louanne Hudgins, Melissa Hurwitz, Jonathan P Palma, Susan Schelley, Vishnu Priya Akula, Marshall L Summar, Gregory M Enns
PURPOSE OF STUDY: Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor...
January 16, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29390191/inducible-knockdown-of-endothelial-protein-tyrosine-phosphatase-1b-promotes-neointima-formation-in-obese-mice-by-enhancing-endothelial-senescence
#6
Marianne Jäger, Astrid Hubert, Rajinikanth Gogiraju, Magdalena L Bochenek, Thomas Münzel, Katrin Schäfer
AIMS: Protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of receptor tyrosine kinase signaling. In this study, we determined the importance of PTP1B expressed in endothelial cells for the vascular response to arterial injury in obesity. RESULTS: Morphometric analysis of vascular lesions generated by 10% ferric chloride (FeCl3) revealed that tamoxifen-inducible endothelial PTP1B deletion (Tie2.ERT2-Cre × PTP1Bfl/fl; End.PTP1B knockout, KO) significantly increased neointima formation, and reduced numbers of (endothelial lectin-positive) luminal cells in End...
February 1, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29382510/preoperative-renal-functional-reserve-predicts-risk-of-acute-kidney-injury-after-cardiac-surgery
#7
Faeq Husain-Syed, Fiorenza Ferrari, Aashish Sharma, Tommaso Hinna Danesi, Pércia Bezerra, Salvador Lopez-Giacoman, Sara Samoni, Massimo de Cal, Valentina Corradi, Grazia Maria Virzì, Silvia De Rosa, María Jimena Muciño Bermejo, Carla Estremadoyro, Gianluca Villa, Jose J Zaragoza, Carlotta Caprara, Alessandra Brocca, Horst-Walter Birk, Hans-Dieter Walmrath, Werner Seeger, Federico Nalesso, Monica Zanella, Alessandra Brendolan, Davide Giavarina, Loris Salvador, Rinaldo Bellomo, Mitchell H Rosner, John A Kellum, Claudio Ronco
BACKGROUND: Although acute kidney injury (AKI) frequently complicates cardiac surgery, methods to determine AKI risk in patients without underlying kidney disease are lacking. Renal functional reserve (RFR) can be used to measure the capacity of the kidney to increase glomerular filtration rate under conditions of physiological stress and may serve as a functional marker that assesses susceptibility to injury. We sought to determine whether preoperative RFR predicts postoperative AKI...
January 27, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29366966/laparoscopic-assisted-uterus-retrieval-from-live-organ-donors-for-uterine-transplant-our-experience-of-two-patients
#8
Shailesh Puntambekar, Milind Telang, Pankaj Kulkarni, Seema Puntambekar, Sanjeev Jadhav, Mangesh Panse, Ravindra Sathe, Nikhil Agarkhedkar, Neeta Warty, Sandesh Kade, Manoj Manchekar, Hirav Parekh, Kajal Parikh, Riddhi Desai, Mehul Mehta, Mihir Chitale, Bhushan Kinholkar, Joy Shankar Jana, Avinash Pare, Abhay Sadre, Swapnil Karnik, Abhay Mane, Giriraj Gandhi, Shailendra Kanade, Uday Phadke
OBJECTIVE: To report the first ever laparoscopic-assisted live donor uterus retrieval in two patients for uterus transplant DESIGN: Case study (Canadian Task Force Classification Level III) SETTING: Galaxy CARE Laparoscopy Institute, Pune, India PATIENT(S): Two patients with AUFI with their mothers as donors. INTERVENTION(S): A twelve member team was formed and approval for transplant was obtained from Institutional Review Board (IRB). Pre transplant, In Vitro Fertilization (IVF) for both patients was done...
January 20, 2018: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/29360030/stop-posturing-and-start-problem-solving-a-call-for-research-to-prevent-gun-violence
#9
Kelsey Hills-Evans, Julian Mitton, Chana A Sacks
Gun violence is a major cause of preventable injury and death in the United States, leading to more than 33,000 deaths each year. However, gun violence prevention is an understudied and underfunded area of research. We review the barriers to research in the field, including restrictions on federal funding. We then outline potential areas in which further research could inform clinical practice, public health efforts, and public policy. We also review examples of innovative collaborations among interdisciplinary teams working to develop strategies to integrate gun violence prevention into patient-doctor interactions in order to interrupt the cycle of gun violence...
January 1, 2018: AMA Journal of Ethics
https://www.readbyqxmd.com/read/29340077/lrp6-targeting-suppresses-gastric-tumorigenesis-via-p14arf-mdm2-p53-dependent-cellular-senescence
#10
Haibin Wang, Guoxing Xu, Zhengjie Huang, Weizheng Li, Huali Cai, Yunda Zhang, Disheng Xiong, Gang Liu, Shengjie Wang, Zengfu Xue, Qi Luo
NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290940/lysophosphatidylcholine-induces-cytotoxicity-apoptosis-and-il-8-production-of-human-endothelial-cells-related-mechanisms
#11
Mei-Chi Chang, Jang-Jaer Lee, Yi-Jane Chen, Szu-I Lin, Li-Deh Lin, Eric Jein-Wen Liou, Wei-Ling Huang, Chiu-Po Chan, Chi-Chia Huang, Jiiang-Huei Jeng
Increased levels of oxidized low-density lipoprotein oxLDL) are shown to elevate the risk of cardiovascular diseases such as atherosclerosis, thrombosis, stroke, and myocardial infarction. This is possibly due to the toxic effects of oxLDLs on vascular cells. Various oxLDLs including lysophosphatidylcholine (LPC) and 7-ketocholesterol injure vascular endothelial cells and stimulate inflammatory reaction. However the toxicity of LPC on endothelial cells is not clear. In this study, human endothelial cells were exposed to LPC...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281643/4-aminopyridyl-based-lead-compounds-targeting-cyp51-prevent-spontaneous-parasite-relapse-in-a-chronic-model-and-improve-cardiac-pathology-in-an-acute-model-of-trypanosoma-cruzi-infection
#12
Claudia Magalhaes Calvet, Jun Yong Choi, Diane Thomas, Brian Suzuki, Ken Hirata, Sharon Lostracco-Johnson, Liliane Batista de Mesquita, Alanderson Nogueira, Marcelo Meuser-Batista, Tatiana Araujo Silva, Jair Lage Siqueira-Neto, William R Roush, Mirian Claudia de Souza Pereira, James H McKerrow, Larissa M Podust
BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections...
December 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29279310/proliferating-ng2-cell-dependent-angiogenesis-and-scar-formation-alter-axon-growth-and-functional-recovery-after-spinal-cord-injury-in-mice
#13
Z C Hesp, R Y Yoseph, R Suzuki, C Wilson, A Nishiyama, D M McTigue
Spinal cord injury (SCI) induces a centralized fibrotic scar surrounded by a reactive glial scar at the lesion site. The origin of these scars is thought to be perivascular cells entering lesions on ingrowing blood vessels and reactive astrocytes, respectively. However, two NG2-expressing cell populations (pericytes and glia) also may influence scar formation. In the periphery, new blood vessel growth requires proliferating NG2+ pericytes; if also true in the CNS, then the fibrotic scar would depend on dividing NG2+ pericytes...
December 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29250830/suppressive-activities-and-mechanisms-of-ugonin-j-on-vascular-smooth-muscle-cells-and-balloon-angioplasty-induced-neointimal-hyperplasia
#14
Chun-Hsu Pan, Pei-Chuan Li, Yi-Chung Chien, Wan-Ting Yeh, Chih-Chuang Liaw, Ming-Jyh Sheu, Chieh-Hsi Wu
Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell-cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry. Cell migration was examined using a wound-healing analysis and a transwell assay. Protein expressions and gelatinase activities were, respectively, measured using Western blot and gelatin zymography...
December 18, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29247448/itraq-based-quantitative-proteomics-reveals-the-new-evidence-base-for-traumatic-brain-injury-treated-with-targeted-temperature-management
#15
Shi-Xiang Cheng, Zhong-Wei Xu, Tai-Long Yi, Hong-Tao Sun, Cheng Yang, Ze-Qi Yu, Xiao-Sa Yang, Xiao-Han Jin, Yue Tu, Sai Zhang
This study aimed to investigate the effects of targeted temperature management (TTM) modulation on traumatic brain injury (TBI) and the involved mechanisms using quantitative proteomics technology. SH-SY5Y and HT-22 cells were subjected to moderate stretch injury using the cell injury controller (CIC), followed by incubation at TTM (mild hypothermia, 32°C), or normothermia (37°C). The real-time morphological changes, cell cycle phase distribution, death, and cell viability were evaluated. Moderate TBI was produced by the controlled cortical impactor (CCI), and the effects of TTM on the neurological damage, neurodegeneration, cerebrovascular histopathology, and behavioral outcome were determined in vivo...
January 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29239994/effects-of-judo-training-on-bones-a-systematic-literature-review
#16
Simone Ciaccioni, Giancarlo Condello, Flavia Guidotti, Laura Capranica
The aim of this study was to provide a systematic literature review on the osteogenic effects of judo (PROSPERO: CRD42016041803). The online search was conducted according to the inclusion criteria: observational studies and clinical/interventional trials in English from inception to June 2016; bone health, mineral density (BMD), diameters, impact force and turnover markers (BTM) outcomes. Thirty-four studies were included and graded for their methodological quality ("fair" quality: 79.4%). The most used assessment method (44...
December 11, 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/29216642/taurine-protects-mouse-spermatocytes-from-ionizing-radiation-induced-damage-through-activation-of-nrf2-ho-1-signaling
#17
Wenjun Yang, Jinfeng Huang, Bang Xiao, Yan Liu, Yiqing Zhu, Fang Wang, Shuhan Sun
BACKGROUND/AIMS: The increasing prevalence of ionizing radiation exposure has inevitably raised public concern over the potential detrimental effects of ionizing radiation on male reproductive system function. The detection of drug candidates to prevent reproductive system from damage caused by ionizing radiation is urgent. We aimed to investigate the protective role of taurine on the injury of mouse spermatocyte-derived cells (GC-2) subjected to ionizing radiation. METHODS: mouse spermatocytes (GC-2 cells) were exposed to ionizing radiation with or without treatment of Taurine...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29209134/metabolically-based-liver-damage-pathophysiology-in-patients-with-urea-cycle-disorders-a-new-hypothesis
#18
Ivan Ivanovski, Miloš Ješić, Ana Ivanovski, Livia Garavelli, Petar Ivanovski
The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs...
November 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29202851/female-genital-tuberculosis-and-infertility-serial-cases-report-in-bandung-indonesia-and-literature-review
#19
Tono Djuwantono, Wiryawan Permadi, Leri Septiani, Ahmad Faried, Danny Halim, Ida Parwati
BACKGROUND: Female genital tuberculosis (FGTB) is a Mycobacterium infection in the reproductive organs which often leads to infertility. FGTB is either asymptomatic or causes uncharacteristic clinical presentations, making an early diagnosis is challenging. Our aims were to evaluate the clinical presentations, the process to confirm the diagnosis and followed-up the patients who had undergone laparoscopy at our center. FGTB has been reported from many countries, but has never been reported from Indonesia...
December 4, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29200635/the-effects-of-the-menstrual-cycle-on-the-static-balance-in-healthy-young-women
#20
Byung Joon Lee, Ki Hun Cho, Wan Hee Lee
[Purpose] The purpose of this study was to investigate the effects of the menstrual cycle on the static balance of healthy young women. [Subjects and Methods] Eighteen healthy young subjects (mean age 19.1 years; weight 57.5 kg; height 159.9 cm) participated in this study. The Good Balance system was used to measure the postural sway speed and velocity moment of subjects in the static standing posture. Subjects were measured for static balance between 1 and 3 days after menstruation and 13 days after menstruation...
November 2017: Journal of Physical Therapy Science
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