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| 1 | Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. | Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 5 |
| 2 | Systematic review of dynamization vs exchange nailing for delayed/non-union femoral fractures显示文摘AIM To analyze the literature on efficacy of dynamamization vs exchange nailing in treatment of delayed and nonunion femur fractures.METHODS Ultimately, 31 peer-reviewed articles with 644 exchanged nailing patients and 131 dynamization patients were identified and analyzed. The following key words were inputted in different combinations in order to search the field of publications in its entirety: 'nonunion', 'delayed union', 'ununited', 'femur fracture', 'femoral fracture', 'exchange nailing', 'dynaiz(s)ation', 'secondary nailing', 'dynamic', 'static', and 'nail revision'. The initial search yielded over 150 results, and was refined based on the inclusion criteria: Only studies reporting on humans, non-unions and delayed unions, and the usage of exchange nailing and/or dynamization as a secondary treatment after failed IM nailing. The resulting 66 articles were obtained through online journal access. The results were filtered further based on the exclusion criteria: No articles that failed to report overall union rates, differentiate between success rates of their reported techniques, or articles that analyzed less than 5 patients. RESULTS Exchange nailing lead to fracture union in 84.785% of patients compared to the 66.412% of dynamization with statistically comparable durations until union(5.193 ± 2.310 mo and 4.769 ± 1.986 mo respectively). Dynamically locking exchange nails resulted in an average union time of 5.208 ± 2.475 mo compared to 5.149 ± 2.366 mo(P = 0.8682) in statically locked exchange nails. The overall union rate of the two procedures, statically and dynamically locked exchange nailing yielded union rates of 84.259% and 82.381% respectively. Therefore, there was no significant difference between the different locking methods of exchange nailing for union rate or time to union at a significance value of P < 0.05. The analysis showed exchange nailing to be the more successful choice in the treatment of femoral non-unions in respect to its higher success rate(491/567 EN, 24/57 dynam, P < 0.0001). However, there was no significant difference between the success rates of the two procedures for delayed union fractures(25/27 EN, 45/55 dynam, P = 0.3299). Nevertheless, dynamization was more efficient in the treatment of delayed unions(at rates comparable to exchange nailing) than in the treatment of non-unions.CONCLUSION In conclusion, after examination of factors, dynamization is recommended treatment of delayed femur fractures, while exchange nailing is the treatment of choice for non-unions. | Jacob E Vaughn Ronit V Shah Tarek Samman Jacob Stirton Jiayong Liu Nabil A Ebraheim | 2018 | World Journal of Orthopedics2018，9，7： | 5 |
| 3 | Characterization of the Yeast Transcriptome显示文摘 | Victor E Velculescu Lin Zhang Wei Zhou Jacob Vogelstein Munira A Basrai Douglas E Bassett Phil Hieter Bert Vogelstein Kenneth W Kinzler | 1997 | Cell1997，，2： | 4 |
| 4 | Azathioprine-induced fever in autoimmune hepatitis显示文摘Underdiagnosis of drug-induced fever leads to extensive investigation and prolongation of hospitalization, and may lead to multiple unnecessary invasive procedures and a wrong diagnosis. Azathioprine is a widely used immunosuppressive drug. We report a case of a 53-year-old female patient diagnosed with autoimmune hepatitis treated with azathioprine, who presented to the emergency room with a 6-wk history of fever and chills without other associated symptoms. Since the patient's fever was of unknown origin, she was hospitalized. All treatment was stopped and an extensive workup to explore the source of fever and chills was performed. Results of chest X-ray, viral, urine, and blood cultures, autoimmune serology, transthoracic and transesophageal echocardiography, and abdominal ultrasound revealed no source of infection. A rechallenge test of azathioprine was performed and the fever and chills returned within a few hours. Azathioprine was established as the definite cause following rechallenge. Fever as an adverse drug reaction is often unrecognized. Azathioprine has been reported to cause druginduced fever in patients with inflammatory bowel disease, rheumatoid arthritis, and sarcoidosis. To the bestof our knowledge there have been no previous reports documenting azathioprine-induced fever in patients with autoimmune hepatitis. The occurrence of fever following the readministration of azathioprine suggests the diagnosis of drug-induced fever, particularly after the exclusion of other causes. A careful rechallenge is recommended to confirm the diagnosis. | Tawfik Khoury Jacob E Ollech Shmuel Chen Meir Mizrahi Meir Shalit | 2013 | World Journal of Gastroenterology2013，19，25： | 3 |
| 5 | Hypoxic training methods for improving endurance exercise performance显示文摘耐力运动表现与很多因素都高度相关,这些因素可以通过高原训练和低氧训练改变,包括增加红细胞量、提高最大有氧运动能力、增加毛细血管密度和提高有氧运动的经济性。针对短期和长期暴露在低氧环境中的生理适应性已有很多研究,发现从短期的不利影响到长期适应的过程可提高在高原和海平面比赛的运动表现。许多高原和低氧训练方案逐步被改良,包括通过在海平面、低、中、高不同海拔,以及自然或人工的海拔中生活和训练的各种组合,产生不同程度的训练效果。部分因素已被证实与低氧训练的个体反应有关,鉴定这些运动员最有可能受益于低氧训练的技术值得进一步研究。本研究建议的高住低练方案为;低海拔地区训练的同时,在足够的高度(2 000-3 000 m)每天至少生活12 h,周期最少为21天。尽管此类高住低练建议普遍存在.但有关高原训练时间和比赛运动表现的关系仍存在争论。 | Jacob A. Sinex Robert E Chapman | 2015 | Journal of Sport and Health Science2015，4，4： | 3 |
| 6 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 7 | Nonsteady radial flow in an infinite leaky aquifer显示文摘 | Hantush M S Jacob C E | 1955 | EOS Transaction American Geopysical Union1955，36，： | 2 |
| 8 | Effect of 1,2-propanediol and dimethylsulphoxide on the meiotic spindle of the mouse oocytes显示文摘 | Van der Elst J van den Abbeel E Jacobs R | 1988 | Hum Reprod1988，3，： | 2 |
| 9 | Sediment-related growth limitation of Elodea nuttallii as indicated by a fertilization experiment显示文摘 | BEST E P WOLTMAN H JACOBS F H | 1996 | Fresh Water Biology1996，36，： | 1 |
| 10 | The 1994 QUASIMEME laboratory performance studies: Chlorobiphenyls and organo-chlorine pesticides in fish and sediment显示文摘 | Jacob D E Boer | 1996 | Marine pollution Bulletin1996，32，89： | 1 |
| 11 | Superresolution reconstruction and its im pact on sensor performance显示文摘 | Cha J H Jacobs E | 2005 | SPIE2005，5784，： | 1 |
| 12 | Culture-independent nmlti-locus variable-number tandem-repeat analysis ( MLVA ) of mycoplasma pneumoniae 显示文摘 | Dumke R Jacobs E | 2011 | J Microbiol Methods2011，86，3： | 1 |
| 13 | Reference population and mara- thon runner sera assessed by highly sensitive cardiac troponln T and commercial cardiac troponin T and I assays显示文摘 | ingels A Jacobs L Michielsen E | 2009 | Clinical Chemistry2009，，01： | 1 |
| 14 | Diamondiferous eclo- gites from siberia: Remnants of Archean oceanic crust显示文摘 | Jacob D Jagoutz E Lowry D | 1994 | Geochimica et Cosmochimica Acta1994，58，： | 1 |
| 15 | Activation volumes for solid-solid transformations in nanocrystals显示文摘 | Jacobs K Zaziski D Scher E C | 2001 | Science2001，293，5536： | 1 |
| 16 | Hepatic phosphatidylethanolamine N-methyltransferase,unexpected roles in animal biochemistry and physiology显示文摘 | LI Z JACOBS R L | 2007 | J Biol Chem2007，282，33： | 1 |
| 17 | Improved glycemic control with decreased hypoglycemia prevents long-term complications in type 2 diabetes patients:long-term simulation analysis using the 'diabetes mellitus model'显示文摘 | Maxion-bergemann S Huppertz E Jacobs LD | 2005 | Int J Clin Pharmacoi Ther2005，43，6： | 1 |
| 18 | Spinal mechanisms contribute to analgesia prodused by epidural sufentanil clmbined with bupivacaine far postoperative analgesia显示文摘 | Joris J L Jacob E A Sessler D I | 2003 | Anesth Analg2003，97，： | 1 |
| 19 | Loss of tumor mark er-immunostaining intensity on stored paraffin slides of hreast cancer显示文摘 | Jacobs T W Prioleau J E Schnitt S J | 1996 | NatlCancer Inst1996，88，15： | 1 |
| 20 | Environmental Pollution显示文摘 | de Boer Jacob Wester Peter G van der Horst Aschwin Leonard Pim E G | 2003 | 122 : 632003，122，： | 1 |
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