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41.
Muntasir HA Bhuiyan MA Ishiguro M Ozaki M Nagatomo T 《Journal of pharmacological sciences》2006,102(2):189-195
Mutations producing constitutively active G-protein coupled receptors have been found in the pathophysiology of several diseases, implying that inverse agonists at the constitutively active receptors may have preferred therapeutic applications. Because of the involvement of 5-HT(2A) receptors in mediating many cardiovascular diseases, constitutively active mutants of the 5-HT(2A) receptor may be responsible for the disease states. Thus, the purpose of the present study was to investigate the inverse agonist activity of sarpogrelate, a selective 5-HT(2A)-receptor antagonist, and its active metabolite, M-1; and we compared their activities with those of other 5-HT(2A)-receptor antagonists such as ritanserin, ketanserin, and cyproheptadine. Using a constitutively active mutant (C322K) of the human 5-HT(2A) receptor, we demonstrated that like other 5-HT(2A)-receptor antagonists, sarpogrelate acts as a potent inverse agonist by significantly reducing basal inositol phosphate levels. However, there were no significant differences between sarpogrelate and other 5-HT(2A)-receptor antagonists for their inverse agonist activity. Compared with the wild type receptor, mutant receptor displayed significantly higher affinity for 5-HT and lower affinity for sarpogrelate. These results indicate that stabilization of the inactive conformation of the 5-HT(2A) receptor may be a key component of the mechanism of action of sarpogrelate. 相似文献
42.
Franz Buchegger Valentina Garibotto Thomas Zilli Laurent Allainmat Sandra Jorcano Hansjörg Vees Olivier Rager Charles Steiner Habib Zaidi Yann Seimbille Osman Ratib Raymond Miralbell 《European journal of nuclear medicine and molecular imaging》2014,41(1):68-78
Purpose
18F-Fluorocholine (FCH) and 11C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers.Methods
The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤5 ng/ml) or RP and salvage RT (9 patients, PSA ≤5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307?±?16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994?±?72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results.Results
PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen’s kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later.Conclusion
Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging. 相似文献43.
Sultana A Zakaria SM Bhuiyan SI Habib A Dey SK Rahman M Basher A 《Mymensingh medical journal : MMJ》2012,21(3):529-532
Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL) and serves as a potential reservoir for Leishmania parasite. The study was aimed to evaluate the spectrum of skin lesions of PKDL in kala-azar endemic areas in Bangladesh. This cross sectional study was carried out to observe the characteristics of skin lesions among 250 PKDL cases. The suspected PKDL patients in highly endemic villages of Fulbaria Upazilla of Mymensingh district.were subjected to a dipstick test (rK39) for kala azar. The median time interval between diagnosing kala-azar and PKDL was 23 month (m-21, r- 0-60 months). The most common skin lesions were multiple symmetrical hypopigmented macules with irregular margins in 179(71.6%) cases followed by erythematous facial induration in 74(29.6%), papular in 33(13.2%), nodular in 28(11.2%) cases, combination of macules, papules, nodules and plaques in 88(35.2%) cases, annular in 7(2.8%) cases and Papillomatous mucosal growth in 2(0.8%) cases. Sites of involvement were mostly in face (92.4%), Trunk (84.8%), extremities (33.2%), oral mucosa and tongue (0.8%) and Genitalia (1.2%). Suspicion of PKDL on the basis of skin lesions will lead to early diagnosis and prompt treatment will impart an important role in prevention and eradication of Leishmaniasis in Bangladesh. 相似文献
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47.
Habib AG 《Scandinavian journal of infectious diseases》2003,35(6-7):416-418
Salmonella aortic aneurysms occasionally affect adjoining organs. This study reports on 2 elderly men with fatal cases of Salmonella enteritidis involving adjacent organs: aortobronchial fistula from a thoracic aneurysm, and renal involvement from an infrarenal aneurysm. The hope of averting a tragic outcome lies in prompt clinical and radiological recognition followed by effective medical and early surgical interventions. 相似文献
48.
G B Habib J Heibig S A Forman B G Brown R Roberts M L Terrin R Bolli 《Circulation》1991,83(3):739-746
BACKGROUND. The influence of coronary collateral vessels on infarct size in humans remains controversial, partly because no previous study has examined the impact of collaterals present at the onset of acute myocardial infarction on infarct size. METHODS AND RESULTS. The present study used the data base of the Thrombolysis in Myocardial Infarction (TIMI) Phase I trial to correlate the presence or absence of angiographically documented collaterals in the initial hours of myocardial infarct evolution with the size of the infarct as assessed by serial measurements of serum creatine kinase (CK). To avoid the confounding effects of reperfusion on enzymatic estimates of infarct size, this report is limited to those 125 patients who failed to recanalize at 90 minutes after administration of tissue plasminogen activator or streptokinase. Patients with angiographically documented collaterals (group A, n = 51) had significantly lower values of peak serum CK than patients without collaterals (group B, n = 74) (1,877 +/- 216 versus 2,661 +/- 212 IU/l, respectively [mean +/- SEM], p = 0.004). Similarly, CK-derived infarct size estimates were significantly lower in group A than in group B (20.6 +/- 2.5 versus 31.4 +/- 2.8 CK gram equivalents, p = 0.001). The infarct size observed in patients with collaterals was less for anterior infarctions as well as for infarctions of other locations; thus, the beneficial effects of collaterals were independent of the site of the infarct. In 65 of the 125 patients who failed to reperfuse, left ventricular ejection fraction (LVEF) was assessed by contrast ventriculography both at initial cardiac catheterization (before thrombolytic therapy) and at hospital discharge. Among the patients who had both studies, global LVEF tended to increase from pretreatment to hospital discharge in group A (from 50.6 +/- 1.8% to 53.4 +/- 1.8%, p = 0.10) but decreased in group B patients (from 50.3 +/- 1.8% to 47.8 +/- 1.7%, p = 0.02). At hospital discharge, global LVEF was greater in patients with coronary collaterals (53.5 +/- 1.7% versus 49.6 +/- 1.7%, p = 0.01). CONCLUSIONS. The results demonstrate that, in patients in whom thrombolytic therapy fails to induce reperfusion, the presence of coronary collateral vessels at the onset of myocardial infarction is associated with limitation of infarct size as assessed enzymatically and with improved ventricular function on discharge as assessed by LVEF. 相似文献
49.
AF Jorm H Christensen AS Henderson PA Jacomb AE Korten A Mackinnon 《Age and ageing》1996,25(2):126-129
Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline. 相似文献
50.