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81.
Oxytocin (OT) itself and the sensitivity of the uterus to OT play a crucial role in the initiation of both normal and pathologically early delivery. It recognition of the complex mechanism of action suggests that specific OT antagonists are of therapeutic value in postponing early contractions. In this study neurohypophyseal hormone analogues containing Sar in position 7, Arg in position 8, and various conformationally restricted or bulky derivatives of phenilalanine and tryptophan amino acids in position 2 were prepared to design more potent and selective OT antagonists. We determined the ligand-receptor binding characteristics of these newly synthetized peptides in the presence of [3H]oxytocin and [3H]vasopressin on isolated guinea-pig uterus, rat liver and kidney inner medulla plasma membranes. In the case of each peptides we calculated the Ki values and the selectivity ratio. The binding to the OT receptor was dramatically decreased for the Trp-derivatives containing analogues, while the Phe-derivatives containing analogues displayed a relatively high receptor affinity and have a relatively high OT/VP1 receptor selectivity. 相似文献
82.
83.
Bányász T Fülöp L Magyar J Szentandrássy N Varró A Nánási PP 《Cardiovascular research》2003,58(1):66-75
OBJECTIVES: The aim of the present study was to assess and compare the dynamics of L-type Ca(2+) current (I(Ca,L)) during physiologic action potential (AP) in canine ventricular cardiomyocytes of epicardial (EPI) and endocardial (ENDO) origin. METHODS: I(Ca,L) was recorded on cells derived from the two regions of the heart using both AP voltage clamp and conventional whole cell voltage clamp techniques. RESULTS: AP voltage clamp experiments revealed that the decay of I(Ca,L) is monotonic during endocardial AP, whereas the current is double-peaked (displaying a second rise) during epicardial AP. The amplitude of the first peak was significantly greater in ENDO (-4.6+/-0.8 pA/pF) than in EPI cells (-2.8+/-0.3 pA/pF). Application of epicardial APs as command pulses to endocardial cells yielded double-peaked I(Ca,L) profiles, and increased the net charge entry carried by I(Ca,L) during the AP from 0.187+/-0.059 to 0.262+/-0.056 pC/pF (n=5, P<0.05). No differences were observed in current densities and inactivation kinetics of I(Ca,L) between EPI and ENDO cells when studied under conventional voltage clamp conditions. Nisoldipine shortened action potentials and eliminated the dome of the epicardial AP. CONCLUSION: I(Ca,L) was shown to partially inactivate before and deactivate during phase-1 repolarization and reopening of these channels is responsible for the formation of the dome in canine EPI cells. The transmural differences in the profile of I(Ca,L) could be well explained with differences in AP configuration. 相似文献
84.
Simon E Péter M Benkó K Horkay E Erdélyi G Péter M Szúcs-Farkas Z Tóth J Kovács I Fülöp B 《Orvosi hetilap》2002,143(14):721-723
INTRODUCTION: The screening mammography decreases the mortality of female breast cancer. METHODS: A complex, independent centre of screening mammography has been operating in Debrecen since 1999. RESULTS: The number of the examinations were 10,399 in 1999 and 13,800 in 2000. The number of explored breast cancer cases were 43 (0.41%) in 1999 and 62 (0.45%) in 2000. CONCLUSION: Although the mortality reduction can be exactly measured after several years, we are convinced that the chances for a better life of these 107 women operated on with breast cancer in early state increased thanks to our project. The results of the breast cancer screening program in Debrecen fulfilled the professional requirements of mammographic service-screening. 相似文献
85.
Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide: the Rotterdam experience 总被引:13,自引:0,他引:13
Valkema R De Jong M Bakker WH Breeman WA Kooij PP Lugtenburg PJ De Jong FH Christiansen A Kam BL De Herder WW Stridsberg M Lindemans J Ensing G Krenning EP 《Seminars in nuclear medicine》2002,32(2):110-122
Fifty patients with somatostatin receptor-positive tumors were treated with multiple doses of [(111)In-diethylenetriamine pentaacetic acid(0)]octreotide. Forty patients were evaluable after cumulative doses of at least 20 GBq up to 160 GBq. Therapeutic effects were seen in 21 patients: partial remission in 1 patient, minor remissions in 6 patients, and stabilization of previously progressive tumors in 14 patients. Our results thus underscore the therapeutic potential of Auger-emitting radiolabelled peptides. The toxicity was generally mild bone marrow toxicity, but 3 of the 6 patients who received more than 100 GBq developed a myelodysplastic syndrome or leukemia. Therefore, we consider 100 GBq as the maximal tolerable dose. With a renal radiation dose of 0.45 mGy/MBq (based on previous studies) a cumulative dose of 100 GBq [(111)In-DTPA(0)]octreotide will lead to 45Gy on the kidneys, twice the accepted limit for external beam radiation. However, no development of hypertension, proteinuria, or significant changes in serum creatinine or creatinine clearance were observed in our patients including 2 patients who received 106 and 113 GBq [(111)In-DTPA(0)]octreotide without protection with amino acids, over a follow-up period of respectively 3 and 2 years. These findings show that the radiation of the short-range (maximal 10 microns) Auger electrons originating from the cells of the proximal tubules is not harmful for the renal function. The decrease in serum inhibin B and concomitant increase of serum FSH levels in men indicate that the spermatogenesis was impaired. 相似文献
86.
Cellular regulatory mechanisms normally maintain a delicate balance between cell proliferation, quiescence and death. The imbalance between these functions resulting from molecular intracellular changes is a key factor in tumorigenesis. Tumor cells detaching from the primary tumor possess a propension for invasion and metastasis formation. These tumor cells can attach, migrate, proliferate and grow in host tissue. The surrounding extracellular matrix (ECM) modulates these functions. It is now widely accepted that cell-matrix interactions play an important role in these processes. Most investigators concentrated their attention on the role of integrins in the above processes. There are, however, only scant data on the role of elastin and its receptors in tumor invasion. Nevertheless, experimental evidence indicates that the 67 kDa elastin-laminin receptor (ELR) subunit plays an important role in tumor invasion by mediating essential tumor cell functions leading to metastases. In this review we will concentrate on the putative role of the 67 kDa ELR subunit in tumor invasion. 相似文献
87.
Background&nbsp;&nbsp;
The outgrowth of new vessels &#8211; angiogenesis &#8211; in the tumour mass is considered to be a limiting factor of tumour growth. To inhibit the matrix lysis that is part of the tumour angiogenesis, we employed the chimeric protein mhATF-BPTI, composed of the receptor binding part of the urokinase (ATF) linked to an inhibitor of plasmin (BPTI). 相似文献88.
Ocular symptoms of 17 myasthenia gravis (MG) patients were examined by electronystagmographic registration of optokinetic nystagmus. The aim of this study was to replace the subjective methods used previously with a more reliable quantitative technique and thus assess ophthalmoplegia and diplopia, important initial symptoms in MG. Slow phase angular speed values of foveolar type optokinetic nystagmus in the horizontal plane at 10, 20 and 30 degrees/s target speed were determined. Measurements were performed before and after administration of Mestinon, a reversible cholinesterase inhibitor. Twelve healthy volunteers were examined as controls under standard conditions. Results showed significant differences between MG patients and control group. Slow-phase angular speed was significantly larger after Mestinon administration (p < 0.001). It is concluded, that the exhaustion of external ocular muscles in MG can be well characterized by the determination of the slow phase angular speed values of optokinetic nystagmus (OKN). The examination of OKN was also recommended for the evaluation of ocular symptoms in other neurological disorders. 相似文献
89.
Nitric oxide inhalation inhibits pulmonary apoptosis but not inflammatory injury in porcine meconium aspiration 总被引:3,自引:0,他引:3
Holopainen R Aho H Laine J Halkola L Kääpä P 《Acta paediatrica (Oslo, Norway : 1992)》1999,88(10):1147-1155
To investigate the possible protective effects of nitric oxide (NO) inhalation in newborns with meconium aspiration, 18 10-12-d-old piglets were studied for 6h after an intratracheal bolus (3 ml/kg) of a 65-mg/ml mixture of human meconium. Twelve of the piglets were treated with continuous NO inhalation at a dose of 1 ppm ( n = 6) or 10 ppm ( n = 6), started 30 min before the insult. Pulmonary haemodynamics and systemic oxygenation were followed, and lung tissue samples were studied for signs of inflammation, evidence of ultrastructural injury and apoptotic cell changes. Inhalation of 10 ppm NO, in contrast to 1 ppm NO, significantly delayed the meconium-induced pulmonary pressure rise and the increase in intrapulmonary shunt fraction, and maintained better oxygenation in the piglets. Histologically and biochemically, treatment with 1 or 10 ppm NO inhalation did not protect the lungs against meconium-induced inflammatory injury. Further, ultrastructural lung tissue analysis revealed a significant amount of alveolar exudate and oedematous alveolar epithelium and endothelium after meconium instillation, also in the lungs treated with NO inhalation. However, the increase in apoptotic epithelial cell deaths, previously shown to be stimulated by intratracheal meconium, was significantly impeded after inhalation of 10 ppm. These results thus show that early continuous NO inhalation controls the rise in pulmonary artery pressure and improves the efficiency of arterial oxygenation, and further prevents the increase in epithelial apoptosis, but does not protect against early inflammatory damage caused by meconium aspiration. 相似文献
90.
Placental site trophoblastic tumor 总被引:7,自引:0,他引:7
Placental site trophoblastic tumor (PSTT) is the rarest disease of the gestational trophoblast. Our two cases will be interesting not only because of the rarity of the disease, but because both were recognized before operation. Since the tumor cells are lined up tightly side by side, this disease must be distinguished primarily from tumors of epithelial origin. The authors highlight that the diagnosis should rely on intense hPL-positivity as well as the ultrastructural image of the tumor. In histologically equivocal cases, the determination of hPL, hCG, and MIB-1 immunologic markers can be recommended as routinely performed morphological examinations. Serum hCG monitoring is recommended to follow the evolution of the tumor. 相似文献