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Quantitative autoradiographic analysis was used to identify regions in the brain of the male primate where androgen binding sites may be involved in the actions of testosterone. Three days after castration, adult male rhesus monkeys received a subcutaneous injection of either dihydrotestosterone propionate (DHTP, 20 mg, n = 6), testosterone propionate (TP, 100 mg, n = 2), or oil vehicle (control males, n = 4). Three hours later, 5 mCi [3H]testosterone was administered as an i.v. bolus. At 60 min, brains were rapidly removed and the left halves were used for autoradiography. In control males, highest percentages of labeled neurons (20-84% using a rigorous Poisson criterion) were observed in the ventromedial, arcuate and premammillary nuclei (n.) of the hypothalamus, medial preoptic n., bed n. of stria terminalis, intercalated mammillary n., lateral septal n. and the medial, cortical and accessory basal n. of the amygdala. Pretreatment with DHTP eliminated labeling in androgen target tissues of the genital tract, and reduced the percentages of labeled neurons to 4-22% of control values in the arcuate, lateral septal, premammillary and intercalated mammillary n., indicating that in these regions testosterone acted predominantly at androgen binding sites. However, in the medial preoptic n., the ventromedial hypothalamic n. and the accessory basal amygdaloid n., DHTP pretreatment resulted in much less blocking which, together with other data, suggested that in these sites, testosterone's actions involved aromatization and interaction with estrogen-binding sites. 相似文献
175.
Ana L Hermogenes Michael Richardson Arinos Magalhaes Armando Yarleque Edith Rodriguez Eladio F Sanchez 《Toxicon》2006,47(4):490-494
Lachesis venom plasminogen activator (LV-PA) is a 33-kDa serine proteinase isolated from bushmaster (Lachesis muta muta) snake venom, which activates the fibrinolytic system in vitro. This study has examined the effect of the plasma proteinase inhibitor alpha2-macroglobulin (alpha2-M) towards LV-PA and compares it with the effect on tissue type plasminogen activator (t-PA). The proteolytic activity of LV-PA alone or previously incubated with human plasminogen (Plg) on the large molecular mass protein substrates, dimethylcasein (DMC) and fibrinogen (Fg) was completely inhibited by human alpha2-M. However, the synthetic peptides Tos-Gly-Pro-Lys-pNA and H-D-Pro-Phe-Arg-pNA (S-2302) were hydrolyzed with almost no reduction in rate. At pH 7.4 and 37 degrees C the proteinase (0.15 microM over 15 min) interacted with alpha2-M, and each mole of alpha2-M bound 2 mol of enzyme. Sodium dodecyl sulfate gel electrophoresis of reduced samples showed that the interaction of alpha2-M with either LV-PA or t-PA preincubated with Plg resulted in the formation of approximately 90 kDa fragments and high molecular mass complexes (Mr 180 kDa), generated by the incubation mixture (LV-PA or t-PA) and Plg. The data suggest that LV-PA is a direct-type PA and its fibrinolytic effect can be reduced by alpha2-M in vivo. 相似文献
176.
Bergner Raoul; Hoffmann Martin; Riedel Klaus-Dieter; Mikus Gerd; Henrich Dirk M.; Haefeli Walter E.; Uppenkamp Michael; Walter-Sack Ingeborg 《Nephrology, dialysis, transplantation》2006,21(4):1019-1023
To cover intermediate sensitive Candida glabrata in ICU patients,fluconazole plasma peak levels at least in the range of 1632µg/ml appear necessary for treatment. Previous studiesdid not reach these fluconazole levels under continuous veno-venoushaemofiltration (CVVHF) with dosages of 200600 mg fluconzoledaily. In the present study, nine patients simultaneously requiringCVVHF for treatment of acute oligoanuric renal failure and antimycotictherapy of Candida septicemia received fluconazole 800 mg/day.Fluconazole plasma levels were determined to evaluate whetherthis dosage is adequate to reach the advised fluconazole levels.Patients were dialysed on two consecutive days with an ultrafiltrationrate (UF) of 1000 ml/h or 2000 ml/h, respectively, in a randomizedorder. The predilution was 800 ml/h and 1800 ml/h, respectively.The treatment was tolerated without adverse effects. All patientsreached plasma fluconazole concentrations between 16 and 32µg/ml, remaining in this range for a minimum of 1 up to24 h with a mean of 9.6 h and a UF rate of 2000 ml/h, and 15.7h with a UF rate of 1000 ml/h. So far, there are no in vivodata on the fluconazole plasma concentrations required for effectivetreatment. However, our data demonstrate, that at least thefluconazole concentrations desirable on the basis of in vitrosusceptibility testing can be reached in critically ill patientson CVVHF in an ICU setting. However, in these patients, 800mg fluconazole/day are necessary to achieve fungicidal drugconcentrations. 相似文献
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Noninvasive Intracranial Cerebral Flow Velocity Evaluation in the Emergency Department by Emergency Physicians 总被引:2,自引:0,他引:2
Michael Shafé MD Michael Blaivas MD RDMS Edmond Hooker MD Leigh Straus BS 《Academic emergency medicine》2004,11(7):774-777
Transcranial Doppler (TCD) is an accepted modality for the evaluation of cerebral blood flow velocities. OBJECTIVES: The purpose of this study was to test the feasibility of bedside TCD measurement in the emergency department (ED) with critically ill, intubated patients. METHODS: A prospective convenience sample of patients presenting to a university hospital over a two-month period underwent TCD evaluation of the middle cerebral artery. Intubated patients with head trauma and any patient requiring tracheal intubation were eligible. A 2-MHz Doppler probe was positioned over the temporal bone to acquire blood flow velocities. An emergency medicine resident and research assistant obtained measurements. Continuous TCD tracings were recorded on a video cassette recorder tape for quality assurance review and data collection. Vital signs and therapeutic interventions were also recorded. Flow velocities were measured in cm/s; the peak Resistance Index (RI) was calculated for each patient. RESULTS: A total of 30 patients were enrolled in the study. Adequate tracings were obtained in 25 patients (83%) without a disruption of resuscitation. Tracings could not be obtained in five patients; they were listed as TCD failures. However, in two of these patients, adequate flow velocity tracings were obtained after resuscitation. Four patients were evaluated during tracheal intubation. One patient was monitored successfully during cardiopulmonary resuscitation. The median time required for data acquisition was 1.9 minutes. The mean highest RI for those who expired was 0.84. For those who survived, the mean highest RI was 0.52. The difference of 0.32 was statistically significant (p = 0.04). CONCLUSIONS: Noninvasive blood flow velocity monitoring of the middle cerebral artery using TCD is feasible in the ED when performed at the bedside on intubated patients with traumatic brain injury and others during tracheal intubation and resuscitation. 相似文献
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Dnyanesh N Tipre Sami S Zoghbi Jeih-San Liow Michael V Green Jurgen Seidel Masanori Ichise Robert B Innis Victor W Pike 《Journal of nuclear medicine》2006,47(2):345-353
18F-FCWAY (18F-trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazin-1-yl)ethyl]-N-(2-pyridyl)cyclohexanecarboxamide) is useful in clinical research with PET for measuring serotonin 1A (5-HT1A) receptor densities in brain regions of human subjects but has significant bone uptake of radioactivity due to defluorination. The uptake of radioactivity in skull compromises the accuracy of measurements of 5-HT1A receptor densities in adjacent areas of brain because of spillover of radioactivity through the partial-volume effect. Our aim was to demonstrate with a rat model that defluorination of 18F-FCWAY may be inhibited in vivo to improve its applicability to measuring brain regional 5-HT1A receptor densities. METHODS: PET of rat head after administration of 18F-FCWAY was used to confirm that the distribution of radioactivity measured in brain is dominated by binding to 5-HT1A receptors and to reveal the extent of defluorination of 18F-FCWAY in vivo as represented by radioactivity (18F-fluoride ion) uptake in skull. Cimetidine, diclofenac, and miconazole, known inhibitors of CYP450 2EI, were tested for the ability to inhibit defluorination of 18F-FCWAY in rat liver microsomes in vitro. The effects of miconazole treatment of rats on skull radioactivity uptake and, in turn, its spillover on brain 5-HT1A receptor imaging were assessed by PET with venous blood analysis. RESULTS: PET confirmed the potential of 18F-FCWAY to act as a radioligand for 5-HT1A receptors in rat brain and also revealed extensive defluorination. In rat liver microsomes in vitro, defluorination of 18F-FCWAY was almost completely inhibited by miconazole and, to a less extent, by diclofenac. In PET experiments, treatment of rats with miconazole nitrate (60 mg/kg intravenously) over the 45-min period before administration of 18F-FCWAY almost obliterated defluorination and bone uptake of radioactivity. Also, brain radioactivity almost doubled while the ratio of radioactivity in receptor-rich ventral hippocampus to that in receptor-poor cerebellum almost tripled to 14. The plasma half-life of radioligand was also extended by miconazole treatment. CONCLUSION: Miconazole treatment, by eliminating defluorination of 18F-FCWAY, results in effective imaging of brain 5-HT1A receptors in rat. 18F-FCWAY PET in miconazole-treated rats can serve as an effective platform for investigating 5-HT1A receptors in rodent models of neuropsychiatric conditions or drug action. 相似文献