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排序方式: 共有263条查询结果,搜索用时 15 毫秒
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33.
Rotella DP 《IDrugs : the investigational drugs journal》1999,2(11):1104-1106
34.
Rotella DP Sun Z Zhu Y Krupinski J Pongrac R Seliger L Normandin D Macor JE 《Journal of medicinal chemistry》2000,43(26):5037-5043
A previous report from these laboratories identified the N-3-benzylimidazoquinazolinone nucleus as a more selective PDE5 inhibitor template compared to the pyrazolopyrimidine of sildenafil. This paper describes in detail the structure-activity relationships of a set of sulfonamide analogues, several of which are both more potent and more selective PDE5 inhibitors in vitro than sildenafil. The synthesis, in vitro enzyme activity and selectivity, and in vitro functional and preclinical pharmacokinetic assessment of molecules in this series are described. 相似文献
35.
Warren G. Darling Nicole Helle Marc A. Pizzimenti Diane L. Rotella Stephanie M. Hynes Jizhi Ge Kimberly S. Stilwell-Morecraft Robert J. Morecraft 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2013,228(1):9-24
The purpose of this study was to test whether brain laterality influences spontaneous recovery of hand motor function after controlled brain injuries to arm areas of M1 and lateral premotor cortex (LPMC) of the hemisphere contralateral to the preferred hand in rhesus monkeys. We hypothesized that monkeys with stronger hand preference would exhibit poorer recovery of skilled hand use after such brain injury. Degree of handedness was assessed using a standard dexterity board task in which subjects could use either hand to retrieve small food pellets. Fine hand/digit motor function was assessed using a modified dexterity board before and after the M1 and LPMC lesions in ten monkeys. We found a strong negative relationship between the degree of handedness and the recovery of manipulation skill, demonstrating that higher hand preference was associated with poorer recovery of hand fine motor function. We also observed that monkeys with larger lesions within M1 and LPMC had greater initial impairment of manipulation and poorer recovery of reaching skill. We conclude that monkeys with a stronger hand preference are likely to show poorer recovery of contralesional hand fine motor skill after isolated brain lesions affecting the lateral frontal motor areas. These data may be extended to suggest that humans who exhibit weak hand dominance, and perhaps individuals who use both hands for fine motor tasks, may have a more favorable potential for recovery after a unilateral stroke or brain injury affecting the lateral cortical motor areas than individuals with a high degree of hand dominance. 相似文献
36.
M L Brandi C M Rotella A Tanini R Toccafondi S M Aloj 《Journal of endocrinological investigation》1987,10(5):451-458
In the presence of Ro 20-1724, a selective inhibitor of cyclic nucleotide phosphodiesterase, carbamylcholine increases cAMP and cGMP levels in human thyroid cells in primary culture. The increase of cAMP exhibited at concentrations of carbamylcholine between 10 fM and 10 pM, is dose- and time-dependent, it is maximum after 30 min and is abolished after 60 min. At higher carbamylcholine concentration (10 microM), cAMP increases rapidly, becoming maximum after 15 min, but returns to unstimulated values after 30 min. The increase of cGMP is also dose-dependent (0.1 nM-10 microM); it reaches the maximum after 30 min and returns to unstimulated values after 120 min. A significant increase of phosphodiesterase activity is observed at 10 microM carbamylcholine. Atropine, a muscarinic receptor antagonist, blocks carbamylcholine effects on both cAMP and cGMP production without affecting the thyrotropin-induced cAMP accumulation. Hexamethonium, a nicotinic receptor antagonist does not affect the cholinergic effects. In the presence of Ro 20-1724, 10 microM carbamylcholine significantly inhibits the effect of thyrotropin on cAMP production, while the combined addition of low doses of carbamylcholine and thyrotropin (0.1 nM and 10 pM, respectively) results in an additive effect on cAMP levels. Inhibition of thyrotropin activity on cAMP production, similar to that exerted by 10 microM carbamylcholine is produced by increasing free intracellular calcium; this inhibition is relieved by using a calmodulin-sensitive phosphodiesterase inhibitor, M and B 22948 at 50 microM dose. High concentrations (10 microM) of carbamylcholine increase the adenylate cyclase activity, without any significant effect on the thyrotropin-induced activation of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
37.
E Mannucci V Ricca E Barciulli M Di Bernardo R Travaglini P L Cabras C M Rotella 《Addictive behaviors》1999,24(3):345-357
The development and validation of a self-reported measure of obesity-related quality of life, the Obesity Related Well-Being (ORWELL 97), were undertaken to examine the intensity and the subjective relevance of physical and psychosocial distress. The questionnaire was validated in a sample of 147 obese patients (99 females, 48 males). The Eating Disorder Examination 12.0D interview, a structured diagnostic interview for DSM-III-R (DSM-IV criteria for binge eating disorder), Beck Depression Inventory, Binge Eating Scale, and the State-Trait Anxiety Inventory 1 and 2 scales were also applied. Internal consistency and test-retest reliability were satisfactory. Factor analysis allowed the identification of two subscales: ORWELL 97-1 related to psychological status and social adjustment, and ORWELL 97-2 related to physical symptoms impairment. Obese female patients showed a lower quality of life, and the severity of obesity appeared to interfere with physical functioning rather than psychological status and social adjustment. The ORWELL 97 questionnaire appears to be a simple and reliable measure of obesity-related quality of life, which can be used in current clinical practice. 相似文献
38.
Thyrotropin-independent mutant clones from FRTL5 rat thyroid cells: hormonal control mechanisms in differentiated cells 总被引:1,自引:0,他引:1
Mutant cells varying in the pathways of their responses to hormonal stimulation are useful in defining the subcellular steps in the mechanisms of hormone action. FRTL5, a strain of normal and differentiated cells originally derived from adult rat thyroids, which depends on TSH for growth in vitro, was used to produce five TSH-independent mutants, after chemical mutagenesis and selection in medium lacking TSH. Their characterization and comparison with wild type cells demonstrated full retention of differentiated thyroid function markers such as thyroglobulin production and active iodide transport, and a slower growth rate. Characterization of cAMP metabolism in mutants revealed levels of basal cAMP and adenylate cyclase and phosphodiesterase activities similar to those of wild type cells kept in a nonproliferative state in medium lacking TSH. Adenylate cyclase responsiveness to very low doses of TSH (10(-12) M) was fully retained in all mutant clones, but the TSH-dependent cAMP elevation, although comparable to that reported in wild type cells, was not followed by significant growth stimulation in mutants. These findings demonstrate that the persistence of functional TSH receptors in these cells and that of growth regulation in them is independent of cAMP elevation. 相似文献
39.
Musilli C Paccosi S Pala L Gerlini G Ledda F Mugelli A Rotella CM Parenti A 《Molecular immunology》2011,49(1-2):234-238
Dendritic cells (DCs) are suspected to be involved in the development of atherogenesis, but their role is still unclear. The aim of this study was to characterize circulating DCs and monocyte-derived DCs (Mo-DCs) of obese and diabetic patients (T2D), and to study their interaction with human coronary smooth muscle cells (CASMCs). Obese post-menopausal women with or without insulin resistance were enrolled and were compared to age-matched healthy women. Myeloid circulating DCs significantly increased in obese T2D patients compared to healthy donors and a smaller increase was observed for plasmacytoid one. Mature Mo-DCs from obese T2D patients significantly decreased when compared to control, but they were significantly more capable of adhering to CASMCs compared to that from healthy controls and from not-T2D obese subjects. Altogether these data suggest that in conditions of insulin-resistance and obesity there is an up-regulation of myeloid DCs that might contribute to pathological vascular remodeling. 相似文献
40.
How many components for the metabolic syndrome? Results of exploratory factor analysis in the FIBAR study 总被引:1,自引:0,他引:1
Mannucci E Monami M Rotella CM 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2007,17(10):719-726
Background and aimsFactor analysis can be used as a basis for the determination of diagnostic criteria for the metabolic syndrome (MS). This approach can be used as a basis for the determination of diagnostic criteria for MS.Methods and resultsExploratory factor analysis of Adult Treatment Panel (ATP)-III and International Diabetes Federation (IDF) criteria for MS, entered as dichotomic variables, was performed on 2945 patients enrolled in a screening programme for diabetes. The ability of calculated factors to identify patients with MS-related conditions (glucose intolerance, hyperuricaemia, and elevation of alanine aminotransferase; ALT) was assessed through Receiver Operator Characteristics (ROC) curve analysis. Alternative sets of criteria based on ATP-III and IDF definitions of MS were also assessed. A two-factor structure was found for both ATP-III and IDF criteria. Factor 1 (associated with fasting hyperglycaemia, hypertension, and elevated waist circumference) was capable of identifying subjects with MS-related conditions to a greater extent than factor 2 (low HDL-cholesterol and hypertriglyceridaemia). When a composite variable (low HDL-cholesterol and/or hypertriglyceridaemia) was used for dislipidaemia, a single factor structure was obtained both for ATP-III and IDF definitions; this factor structure was retained when hyperuricaemia was added as a fifth component of MS. Such a modified definition of MS was not inferior to original ATP-III and IDF criteria in the identification of subjects with glucose intolerance and elevated ALT.ConclusionsA modification of current ATP-III or IDF criteria is necessary in order to obtain a single-factor structure. Alternative definitions of MS, including additional features, such as hyperuricaemia, can maintain a monofactorial structure, and an association with related conditions not inferior to that of original criteria. 相似文献