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| 1 | Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice显示文摘BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications. | Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews | 2020 | World Journal of Gastroenterology2020，26，23： | 3 |
| 2 | Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease显示文摘 | Aaron S D Vandemheen K L Hebert P | 2003 | N Engl J Med2003，348，： | 1 |
| 3 | Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease 显示文摘 | Aaron S D Vandemheen K L Hebert P | 2003 | N Engl J Med2003，348，26： | 1 |
| 4 | Interleukin-10 regulation in normal subjects and patients with asthma显示文摘 | Borish L Aarons A Rumbyrt J Cvietusa P Negri J Wenzel S | 1996 | J Allergy Clin Immunol1996，97，6： | 1 |
| 5 | Impact of chronic congestive heart failure on pharmacokinetics and vasomotor effects of infused nitrite显示文摘 | Abdul R Maher Sayqa Arif Melanie Madhani Khalid Abozguia Ibrar Ahmed Bernadette O Fernandez Martin Feelisch AG O’Sullivan Arthur Christopoulos Aaron L Sverdlov Doan Ngo Rustem Dautov Philip E James John D Horowitz Michael P Frenneaux | 2013 | Br J Pharmacol2013，，3： | 1 |
| 6 | New Models for Old Questions: Generalized Linear Models for Cost Prediction 显示文摘 | Moran J L Solomon P J Aaron P R | 2007 | Journal of Evaluation in Clinical Practice2007，，3： | 1 |
| 7 | Lumping of whole-body physiologically based pharmacokinetic models显示文摘 | NESTOROV I A AARONS L J ARUNDEL P A | 1998 | J Pharmacokinet Biopharm1998，26，1： | 1 |
| 8 | Dehydrating conflict 显示文摘 | SANDRA L P AARON T W | 2001 | Foreign Policy2001，126，910： | 1 |
| 9 | Production of α-1,3-galactosyltransferase knockout Pigs by nuclear transfer cloning显示文摘 | Donna K S Kwang W P Hee T C Julia L G Gi S I Melissa S Aaron B August R Billy N D Clifton N M David B C Robert J H Randall S P | 2002 | Science2002，295，5557： | 1 |
| 10 | Suppression subtractive hybridization: A method for generating differentially regulated or tissue-specific cDNA probes and libraries 显示文摘 | Luda D Yun-Fai C L Aaron P C | 1996 | Proc Natl Acad Sci USA1996，93，： | 1 |
| 11 | Middle ear adenomas stain for two cell populations and lack myoepithelial cell differentia- tion显示文摘 | Abberly A Lott L Aaron P | 2012 | Head Neck Pathol2012，6，3： | 1 |
| 12 | Thermoregulatory behavior of the crayfish Procambarus clarkii in a burrow environment显示文摘 | Aaron L P Iain J M | 2003 | Comparative Biochemistry and Physiology Part A2003，136，： | 1 |
| 13 | Linages,sublineages and variants of enterovirus 68in recent outbreaks显示文摘 | Lauinger I L Bible J M Halligan E P Aarons E J MacMahon E Tong C Y | 2012 | PLoS One2012，7，36： | 1 |
| 14 | Thermoregulatory behavior of the crayfish (Procambarus clarkii) in a burrow environment 显示文摘 | Aaron L P Iain J M | 2003 | Comp Biochem Physiol A2003，136，： | 1 |
| 15 | Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin显示文摘 | Shirly P Aaron G R Hongyan L | 2004 | Science2004，304，： | 1 |
| 16 | Thermoregulatory behavior of the crayfish (Procambarus clarkia) in a burrow environ- ment显示文摘 | Aaron L P lain J M | 2003 | Compar Biochem Physiol Part A2003，136，： | 1 |
| 17 | Prevalence of mixed cryoglobulins in relation to CD4 cell count among patients coinfected with HIV and hepatitis C virus显示文摘 | Aaron L Lebray P Alyanakian MA | 2005 | Clin Infect Dis2005，40，2： | 1 |
| 18 | Magnetically controlled growing instrumentation for early onset scoliosis: Caution needed when interpreting the literature显示文摘BACKGROUND Magnetically controlled growing rods(MCGR) are a novel treatment option for early onset scoliosis(EOS). Although the complication profile with MCGR use has been reviewed, these reviews do not take into account important implants modifications, termed iterations, that were made due to early on postoperative complications is not well reported or understood.AIM To assess the effect of MCGR implant iterations on post-operative complications in EOS.METHODS A systematic review was performed to identify studies investigating MCGR specifically for the treatment of EOS, refined to those reporting the implant iteration, specifically the incorporation of the keeper plate to the implant design.Articles with mixed implant iteration usage were excluded. Complications following surgery were recorded as well as potential risk factors and compared between implant cohorts.RESULTS Although 20 articles were identified for inclusion, 5 included mixed implant iteration leaving a total of 271 patients identified through 15 clinical studies thatmet inclusion criteria. The average follow-up was 25.4-mo. Pre-keeper plate implants were utilized in 3 studies with a total of 49 patients. Overall, 115(42.4%)post-operative complications were identified, with 87% defined as major. The addition of the keeper plate significantly decreased the rate of post-operative complications per study(35.7% vs 80.6%, P = 0.036), and the rate of distraction failure(8.1% vs 40.8%, P = 0.02). Unplanned reoperation occurred in 69(26.7%)patients but was not different between implant iteration cohorts(25.5% without keeper plate vs 27.1% with keeper plate, P = 0.92).CONCLUSION MCGR for EOS has a cumulative complication rate of 42.4% but this is significantly reduced to 35.7% when reviewing only keeper-plate enabled implants. However, 25% of published articles included mixed implant iterations.Future studies should discern between implants iterations when reporting on the usage of MCGR for EOS. | Kenneth Aaron Shaw Justin M Hire Scott Kim Dennis P Devito Michael L Schmitz Joshua S Murphy | 2019 | World Journal of Orthopedics2019，10，11： | 0 |
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