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71.
S Sinha S Gupta S Malhotra NS Krishna AV Meru V Babu V Bansal M Garg N Kumar A Chugh A Ray 《British journal of pharmacology》2010,160(5):1119-1127
Background and purpose:
AE9C90CB (N- [(1R, 5S, 6R)-3-azabicyclo [3.1.0] hex-6-ylmethyl]-2-hydroxy-N-methyl-2, 2-diphenylacetamide), a novel muscarinic receptor antagonist, was synthesized for the treatment of overactive bladder. Here we describe the in vitro and in vivo profiles of AE9C90CB for action in bladder over salivary gland and compare it with four agents already in clinical use (tolterodine, oxybutynin, solifenacin and darifenacin).Experimental approach:
Radioligand binding assay and isolated tissue-based functional assay were used to evaluate affinity, potency, and receptor subtype selectivity of compounds. Inhibition of carbachol-induced increase in intravesicular pressure and salivary secretion were measured in anaesthetized rabbits to assess the functional selectivity.Key results:
In vitro radioligand binding study using human recombinant muscarinic receptors showed that AE9C90CB had greater affinity for M3 muscarinic receptors with pKi of 9.90 ± 0.11 and was 20-fold more selective for M3 than for M2 muscarinic receptors. AE9C90CB exhibited an unsurmountable antagonism on rat bladder strips (pKB, 9.13 ± 0.12). In anaesthetized rabbits after intravenous administration, AE9C90CB dose dependently inhibited carbachol-induced increase in intravesicular pressure and salivary secretion, and exhibited functional selectivity for urinary bladder over salivary gland which was ninefold better than that of oxybutynin.Conclusions and implications:
We have identified AE9C90CB, a compound exhibiting moderate selectivity for M3 over M2 receptors but greater selectivity for urinary bladder over salivary gland than oxybutynin, tolterodine, solifenacin and darifenacin. Therefore, AE9C90CB may be a promising compound for the treatment of overactive bladder with reduced potential to cause dry mouth than currently available antimuscarinic drugs. 相似文献72.
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The relationship between urinary calcium, sodium, and potassium excretion and the role of potassium in treating idiopathic hypercalciuria 总被引:1,自引:0,他引:1
OBJECTIVES: 1) To evaluate the relationships between urinary sodium (UNa), potassium (UK), and calcium (UCa) excretion in the pediatric population; and 2) to determine the effect of increasing potassium intake in patients with idiopathic hypercalciuria and investigate whether this intervention can be offered as another mode of therapy in this patient population. DESIGN: Prospectively, we determined UNa, UK, UCa, and creatinine (Cr) concentrations in randomly collected urine samples from children on initial evaluation for urinary frequency, dysuria, hematuria, enuresis, or kidney stones to identify children with hypercalciuria. SETTING: The outpatient renal clinic of an academic hospital. PARTICIPANTS: Twenty-three black children (13 girls and 10 boys) and 77 white children (44 girls and 33 boys) 3.92 to 16.67 years of age. INTERVENTIONS: Eleven children with hypercalciuria were given potassium supplementation or placed on a high-potassium diet for at least 2 weeks. OUTCOME MEASURES: UNa to UK, UNa to Cr, UK to Cr, and UCa to Cr ratios were calculated from measured levels of urinary minerals. These were repeated in 11 hypercalciuric patients after 2 weeks of increased potassium intake. RESULTS: A total of 100 urine samples were analyzed. The UCa/Cr ratio in blacks 0.04 +/- 0.06 (mean +/- standard deviation) was significantly lower than in whites 0.16 +/- 0.12. There were 21 hypercalciuric white children versus only 1 black child. Linear regression analysis revealed a positive direct correlation between UNa/Cr and UCa/Cr in all 100 subjects and in whites alone but not in blacks. An inverse relationship existed between UK/Cr and UCa/Cr in all subjects and in whites and showed a strong trend in blacks. A marked direct relationship was found between UNa/K and UCa/Cr in all subjects (r = .43) as well as in whites (r = .59) and blacks (r = .49). One black child and 10 white hypercalciuric children were treated with "extra" K for at least 2 weeks. The UNa/K decreased from 4.73 +/- 2.28 to 1.98 +/- 1.09, and the UCa/Cr decreased from 0. 31 +/- 0.10 to 0.14 +/- 0.07, with resolution or improvement of the patients' symptoms. CONCLUSIONS: In our patient population with urinary symptoms, the UCa/Cr ratio in black children is lower and hypercalciuria less common than in white children. In both white and black populations, the UNa/K ratio had the strongest association with the UCa/Cr ratio, indicating an opposing role of UNa and UK on the UCa/Cr ratio. Increased potassium intake was found to be beneficial for hypercalciuric children by decreasing the UNa/K ratio and, consequently, the UCa/Cr ratio. 相似文献
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Pancreatic fistula after pancreatectomy: Evolving definitions, preventive strategies and modern management 总被引:1,自引:0,他引:1
Pancreatic resection is the treatment of choice for pancreatic malignancy and certain benign pancreatic disorders. However, pancreatic resection is technically a demanding procedure and whereas mortality after a pancreaticoduodenectomy is currently 〈 3%-5% in experienced high-volume centers, post-operative morbidity is considerable, about 30%-50%. At present, the single most significant cause of morbidity and mortality after pancreatectomy is the development of pancreatic leakage and fistula (PF). The occurrence of a PF increases the length of hospital stay and the cost of treatment, requires additional investigations and procedures, and can result in life-threatening complications. There is no universally accepted definition of PF that would allow standardized reporting and proper comparison of outcomes between different centers. However, early recognition of a PF and prompt institution of appropriate treatment is critical to the prevention of potentially devastating consequences. The present article, reviews the evolution of post resection pancreatic fistula as a concept, and discusses evolving definitions, the current preventive strategies and the management of this problem. 相似文献
78.
目的:中性粒细胞粘附在缺血再灌注损伤中有非常重要的作用。本文用SD大鼠趾长屈肌缺血再灌注损伤模型,观察L一粘附素单抗LAM1—116在缺血再灌注损伤中的作用。方法:30只SD大鼠被均分为2组:LAM1—116组和生理盐水对照组。每只大鼠的一侧趾长屈肌作为正常对照,另外一侧进行 3 h缺血 4 h再灌注。结果:LAM1— 116组实验侧的髓过氧化物酶为正常的2倍(2.3±2.2),生理盐水对照组则为正常的28倍(27.5±11.7)(P<0.001);LAM1—116组的湿重比(1.10± 0.10)、疲劳肌力(77. 1%±12.1%)与对照组相比(分别为 1. 23± 0. 10和 49. 7%± 9 .3%)明显改善(P< 0.05);组织学上,LAM1—116组的中性粒细胞局部浸润显著减少,水肿减轻。结论:通过 L-粘附素单克隆抗体 LAM1— 116阻断 L-粘附素的功能,可以有效地降低中性粒细胞在再灌注肌肉中的浸润,防止组织水肿,从而改善肌肉的功能。 相似文献
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80.
Rakhmanin YA Ivanova LV Artyemova TZ Gipp EK Zagainova AV Maksimkina TN Krasnyak AV Zhuravlyev PV Aleshnya VV 《实用预防医学》2016,23(11):1400-1409
俄罗斯不同气候地区不同功能水体中克雷伯菌属广泛分布。克雷伯菌属可见于遭受生物、化学污染的集中供水的地表水源,无防护的地下蓄水层,缺乏有效清洁、消毒系统的饮用水。研究表明,水体中的克雷伯菌属具有致病性和毒性,对现代药物和消毒剂(氯、紫外线)具有抗性,很容易穿透进入地下蓄水层。克雷伯菌属细菌有很强的致病性(粘附力、侵袭力、磷酸酯酶、卵磷脂酶、脱氧核糖核酸酶、溶血活性),含有致病性遗传标记cnf-1。克雷伯菌属(100 CFU/dm3)可引起急性肠道感染。在不检测总大肠菌群的情况下,检测水体尤其是饮用水中的克雷伯菌属,可以评估所用水的流行病学危险。 相似文献