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51.
David G Witte Michael E Brune Sweta P Katwala Ivan Milicic Deanne Stolarik Yu-Hua Hui Kennan C Marsh James F Kerwin Michael D Meyer Arthur A Hancock 《The Journal of pharmacology and experimental therapeutics》2002,300(2):495-504
Fiduxosin is a new alpha(1)-adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC(50) values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC(50) values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC(50)/IUP IC(50), were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of alpha(1)-adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an alpha(1a)-/alpha(1d)-subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist. 相似文献
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53.
Limb asymmetries in landing and jumping 2 years following anterior cruciate ligament reconstruction. 总被引:1,自引:0,他引:1
Mark V Paterno Kevin R Ford Gregory D Myer Rachel Heyl Timothy E Hewett 《Clinical journal of sport medicine》2007,17(4):258-262
OBJECTIVE: Female athletes who are at increased risk for anterior cruciate ligament (ACL) injury demonstrate biomechanical differences between limbs during athletic tasks that may persist following anterior cruciate ligament reconstruction (ACLR). This may limit an athlete's potential for safe return to sports competition. The purpose of this study was to determine if female athletes demonstrate lower limb asymmetries in landing and takeoff force following ACLR and clearance for return to competitive sports participation. We hypothesized that females following ACLR would demonstrate side-to-side differences in landing and jumping kinetics after their return to sport (2+ years) that would not be observed in a group of healthy female controls. DESIGN: Case control study. SETTING: The Sports Medicine Biodynamics Center at Cincinnati Children's Hospital Medical Center. PATIENTS: Fourteen female athletes at a mean of 27 months following ACLR and 18 healthy female athletes participated in the study. ASSESSMENT: All subjects executed a drop vertical jump (DVJ) task onto 2 force plates. Vertical ground reaction force (VGRF) was measured during landing and takeoff and was used to calculate landing phase loading rates. A 2-way analysis of variance was used to determine differences between the involved, uninvolved, and control limbs. RESULTS: Females who had undergone ACLR demonstrated increased VGRF (P = 0.001) and loading rate (P < 0.001) on the uninvolved limb during landing when compared with the involved limb and the control group. During takeoff, the involved limb showed significantly less ability to generate force (P = 0.03) than the uninvolved limb and the control limbs. CONCLUSIONS: Female athletes who have undergone ACLR and returned to sport may continue to demonstrate biomechanical limb asymmetries 2 years or more after reconstruction that can be identified during landing. 相似文献
54.
Becker Kavin G.; Nagle James W.; Canning Rachel D.; Biddison William E.; Ozato Keiko; Drew Paul D. 《Human molecular genetics》1995,4(4):685-691
C2H2-type zinc finger genes comprise one of the largest genefamilies in the human genome. These proteins are involved ingenetic regulation and development and are quite conserved throughoutevolution. The finger domains commonly contain the small linkerpeptide TGEKP between some finger units. Here, we report theisolation of 133 human zinc finger cDNAs, of which 118 are novel.These clones were isolated from human brain cDNA libraries usingoligonucleotide hybridization followed by expressed sequencetag (EST) analysis, sequencing from the conserved linker regionusing degenerate oligonucleotide primers. This directed partialsequencing approach to cDNA isolation and characterization,signature sequencing, combines the speed of EST automatic sequencingwith the focus of specific cDNA family analysis. Signature sequencingminimizes the generation of less informative random EST sequencesand provides a unique relative position for sequence comparison.We also show that there is an even distribution of these RNA5from this brain cDNA library, and that these cDNAs contain N-terminaldomains found in other zinc finger genes. This rapid focusedsequencing approach should be applicable to any family of cDNAscontaining short conserved signature peptide sequences. 相似文献
55.
Rachel Yehuda Ann Steiner Boaz Kahana Karen Binder-Brynes Steven M. Southwick Shelly Zemelman Earl L. Giller 《Journal of traumatic stress》1997,10(1):93-100
Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust survivors using the Toronto Alexithymia Scale—Twenty Item Version (TAS-20). Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress disorder (PTSD) were compared, and associations among alexithymia, severity of trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS-20 scores were significantly associated with severity of PTSD symptoms, but not with severity of trauma. This study adds to our knowledge of the relationship between alexithymia and trauma by demonstrating that this characteristic is related to the presence of posttraumatic symptoms and not simply exposure to trauma. 相似文献
56.
57.
Douglas M. Howarth Martin T. Epstein Paul A. Thomas Leonard W. Allen Rachel Akerman Linda Lan 《European journal of nuclear medicine and molecular imaging》1997,24(12):1465-1469
The efficacy of fractionated out-patient radioiodine therapy in 38 patients with compressive symptoms due to long-standing
large multinodular goitres was assessed. The diagnosis was established by clinical assessment in addition to technetium-99m
pertechnetate thyroid scan or computed tomography scan of the thyroid and mediastinum. Oral iodine-131 therapy was administered
as a 2.22 GBq (60 mCi) cumulative dose over 4 months (555 MBq per month). All patients were monitored with serum thyroid-stimulating
hormone and free thyroxine (± free tri-iodothyronine) assays before the treatment and after each dose fraction. Clinical and
biochemical follow-up was performed on all patients and ranged from 6 to 45 months after therapy. The patients consisted of
35 female and three male patients with a median age of 59 years (range 37–87 years). Prior to treatment 20 patients were biochemically
hyperthyroid and 18 were euthyroid. Overall, 71% of patients reported a subjective improvement in compressive symptoms and
29% reported no change. Clinically assessed reduction in goitre size occurred in 92% of patients while there was no change
in 8%. At 3 months of follow-up, 31% of patients had become hypothyroid and at 18 months 66% were hypothyroid. Seven hyperthyroid
patients (35%) became euthyroid and 13 hyperthyroid patients (65%) became hypothyroid. Three patients who became hypothyroid
experienced neck soreness (transient in one patient, persistent in two patients). There were no differences in outcome between
patients who were hyperthyroid and those who were euthyroid prior to treatment. Fractionated out-patient radioiodine therapy
showed excellent short- and medium-term safety, was very well tolerated and offered a satisfactory alternative treatment to
surgery.
Received 23 May and in revised form 11 August 1997 相似文献
58.
Geraldo F. Busatto Lyn S. Pilowsky Durval C. Costa John Mertehs Dirk Terriere Peter J. Ell Rachel Mulligan Michael J. Travis Josée E. Leysen Dominic Lui Sveto Gacinovic Wendy Waddington Anne Lingford-Hughes Robert W. Kerwin 《European journal of nuclear medicine and molecular imaging》1997,24(2):119-124
The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands.
Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (123I-5-I-R91150 or123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary123I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately
2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice
multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free
from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately
100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100
min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic
data on the distribution of 5-HT2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET. 相似文献
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60.