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61.
Recent studies on histamine receptor (HR) subtypes identified imidazolyl butyl cyanoguanidines, like UR‐PI376, as highly potent agonists at the human histamine H4 receptor (hH4R). While imidazole‐containing compounds display drawbacks in pharmacokinetics, we studied the possibility of replacing the heteroaromatic cycle by nonaromatic six‐membered heterocycles (piperidine, morpholine, thiomorpholine, and N‐methylpiperazine) as potential bioisosteres. Beyond that, this approach should give more information about the indispensability of the aromatic ring as a basic head group. Besides these changes, a variation of the spacer length (C3–C5) connecting the heterocycle and the cyanoguanidine moiety has been made to possibly trigger the selectivity towards the respective HRs. Investigations in radioligand‐binding assays exhibited only very weak activity at the hH1R and hH3R, while nearly all compounds were inactive at the hH2R and hH4R. In the case of piperidine‐containing compounds, moderate affinities at the hH3R over the single‐digit micromolar range were detected. 相似文献
62.
Gamliel-Lazarovich A Abassi Z Khatib S Tavori H Vaya J Aviram M Keidar S 《Atherosclerosis》2012,222(1):92-98
AimSerum paraoxonase 1 (PON1) is an HDL-associated lipolactonase and its association with hypertension is controversial. We studied the possible role of PON1 in blood pressure (BP) regulation, by using PON1 knockout (PON1KO) mice.Methods and resultsBoth, systolic and diastolic BPs were lower in PON1KO compared to WT mice. Hypotension detected in PON1KO is probably neither related to nitric oxide/guanylate cyclase-mediated vasodilation nor to angiotensin II or aldosterone-mediated vasoconstriction. Surprisingly, when challenged by high-salt diet, BP was further reduced in PON1KO mice. The later, pointed to a possible involvement of transient receptor potential vanilloid 4 (TRPV4), and indeed, administration of ruthenium red, a TRPV4 blocker, resulted in a sharp rise in BP. The protein levels of TRPV4 in kidneys of PON1KO were not higher than in WT. However, the renal level of 5,6-epoxyeicosatrienoic acid (5,6-EET), a TRPV4 specific agonist, was significantly higher in PON1KO compared with WT mice. 5,6-EET levels were further elevated under high-salt diet or administration of arachidonic acid. Injection of inhibitor of CYP450 epoxygenase resulted in increased BP in PON1KO mice. Injection of recombinant human PON1 resulted in elevation of BP and a concomitant reduction in renal content of 5,6-EET. PON1, in vitro, metabolized 5,6-EET, but not other EETs, to its corresponding diol. Vasodilation, blocked by excess of dietary K+ but not reversed by depletion of cellular Ca2+ stores, point to endothelial-derived hyperpolarization-like response.ConclusionThe present study shows causal, direct relationship between PON1 and blood pressure which is mediated, at least in part, by the regulation of 5,6-EET. 相似文献
63.
Heart disease and stroke statistics--2012 update: a report from the American Heart Association 总被引:1,自引:0,他引:1
Roger VL Go AS Lloyd-Jones DM Benjamin EJ Berry JD Borden WB Bravata DM Dai S Ford ES Fox CS Fullerton HJ Gillespie C Hailpern SM Heit JA Howard VJ Kissela BM Kittner SJ Lackland DT Lichtman JH Lisabeth LD Makuc DM Marcus GM Marelli A Matchar DB Moy CS Mozaffarian D Mussolino ME Nichol G Paynter NP Soliman EZ Sorlie PD Sotoodehnia N Turan TN Virani SS Wong ND Woo D Turner MB;American Heart Association Statistics Committee Stroke Statistics Subcommittee 《Circulation》2012,125(1):e2-e220
64.
To assess the possible association between the protein tyrosine phosphatases non-receptor 22 (PTPN22) gene 1858 CT polymorphism and the predisposition to systemic lupus erythematosus (SLE) in Egyptian patients and its influence on clinical and laboratory parameters. PTPN22 gene 1858 CT polymorphisms were analyzed in forty SLE patients and 20 normal controls by real-time polymerase chain reaction (PCR) technology, using the TaqMan 5-allele discrimination assay. Detailed history, clinical examination, and investigations were done to detect various organ involvement. The homozygous genotype TT was absent in both SLE and controls. The CC genotype was observed in 47.5% SLE and 80% controls; the CT genotype was found in 52.5% patients and 20% controls. The frequencies of the C and T alleles were 74 and 26% in SLE and 90 and 10% in controls, respectively. The presence of CT genotype increased the risk for developing SLE by 4.42. Renal involvement was significantly higher in SLE patients with CT (76.2%) compared to those with CC genotype (42.1%). 相似文献
65.
Hesham Magdi Soliman 《European spine journal》2013,22(5):1037-1044
Purpose
The purpose of this study is to present a new endoscopic procedure, aiming to achieve the success rate equivalent to microsurgical discectomy, while addressing the drawbacks and limitations of other percutaneous techniques.Methods
A series of 43 patients with uncontained lumbar disc herniation underwent surgery with irrigation endoscopic discectomy (IED). The endoscope and instruments are placed directly over the surface of the lamina through two posterior skin portals 5 mm each without any muscle retraction or dilatation. Pump irrigation is used for the opening of a potential working space. The rest of the procedure is performed endoscopically like the standard microsurgical discectomy.Results
Outcome according to modified Macnab criteria was excellent in 78 %, good in 17 %, and poor in 5 % of patients. VAS for leg pain dropped from 78 preoperatively to 7, and the Oswestry Low-Back Pain Disability Questionnaire dropped from 76 to 19. The mean time for postoperative ambulation was 4 h, hospital stay was 8 h, and for return to work was 7 days.Conclusions
Preliminary clinical experience with IED shows it to be as effective as microsurgical discectomy, and in comparison to other percutaneous procedures addressing noncontained herniations, a reduction in the cost, technical difficulty and surgical invasiveness has been demonstrated. 相似文献66.
Skeletal Radiology - The purpose of this article is to describe the sonographic and radiographic findings in the diagnosis and treatment of posterior tibial tendon dysfunction. Ultrasound and... 相似文献
67.
Feasibility of a reduced field‐of‐view diffusion‐weighted (rFOV) sequence in assessment of myometrial invasion in patients with clinical FIGO stage I endometrial cancer 下载免费PDF全文
68.
Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post‐transplant CDT monitoring for alcohol relapse assessment – a retrospective study 下载免费PDF全文
Dagmar Kollmann Susanne Rasoul‐Rockenschaub Irene Steiner Edith Freundorfer Georg Philipp Györi Gerd Silberhumer Thomas Soliman Gabriela Andrea Berlakovich 《Transplant international》2016,29(5):559-567
Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post‐LT long‐term observation is challenging, and biomarkers as carbohydrate‐deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow‐up was 73 months (0–213). One‐ and five‐year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post‐transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single‐center analysis showed good post‐transplant long‐term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post‐LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse. 相似文献
69.
Chronic Mastitis in Egypt and Morocco: Differentiating between Idiopathic Granulomatous Mastitis and IgG4‐Related Disease 下载免费PDF全文
70.
Hasan Soliman Yusufoglu Nurhayat Tabanca Ulrich R. Bernier Andrew Y. Li Mohammed Ayman Salkini Saleh Ibrahim Alqasoumi Betul Demirci 《Saudi Pharmaceutical Journal》2018,26(6):860-864
The essential oils (EOs) of Anthemis melampodina (Am) and Anthemis scrobicularis (As) (Asteraceae) were extracted from the aerial parts of the plants by hydrodistillation, and their chemical compositions were analyzed using GC-FID and GC-MS. Fifty-six components representing 85.5% of the oil composition of Anthemis melampdina were identified, and the major components were α-pinene (17.1%) and β-eudesmol (13.8%). Forty-one components representing 86% of the oil composition of Anthemis scrobicularis were identified, and the major component was β-eudesmol (12.8%). Laboratory bioassays were conducted to determine repellency of Am and As EOs against the yellow fever mosquito Aedes aegypti L. and the lone star tick Amblyomma americanum L. The minimum effective doses (MEDs) of the Am and As EOs against mosquitoes were 0.187?±?0.000 and 0.312?±?0.063?mg/cm2 respectively, which were significantly higher than that of DEET (0.023?±?0.000?mg/cm2) in human-based repellent bioassays. The As EO was more repellent than Am EO against nymphal ticks but was less effective than DEET in vertical paper bioassays. 相似文献