In vivo imaging of brain androgen receptors in rats: a [18F]FDHT PET study

AbstractIntroductionSteroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[18F]fluoro-5α-dihydrotestosterone ([18F]FDHT) to image AR expression in the brain.MethodsMale Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [18F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution.ResultsPET imaging and ex vivo biodistribution studies showed low [18F]FDHT uptake in all brain regions, except pituitary. [18F]FDHT uptake in the surrounding cranial bones was high and increased over time. [18F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [18F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone.ConclusionThe results of this study indicate that imaging of AR availability in rat brain with [18F]FDHT PET is not feasible. The low AR expression in the brain, the rapid metabolism of [18F]FDHT in rats and the poor brain penetration of the tracer likely contributed to the poor performance of [18F]FDHT PET in this study

Association Of Lipophilic Opioids And Hyperbaric Bupivacaine In Spinal Anesthesia For Elective Cesarean Section. Randomized Controlled Study

PURPOSE: To evaluate the efficacy and side-effects of fentanyl and sufentanil combined with hyperbaric spinal bupivacaine in elective cesarean section.METHODS: A prospective, randomized, double-blind study with 64 term parturients, distributed into 2 groups according to the opioid combined with hyperbaric bupivacaine 0.5% (10mg): GF - fentanyl (25μg) and GS - sufentanil (5.0μg). The latency and maximum sensory block level; degree and duration of motor block; duration and quality of analgesia; maternal-fetal repercussions were evaluated. This was an intention-to-treat analysis with a 5% significance level.RESULTS: The latency period, maximum sensory block level, motor block degree and perioperative analgesia were similar in both groups. Motor block and analgesia had a longer duration in the sufentanil group. Maternal adverse effects and neonatal repercussions were similar. The incidence of hypotension was higher in the fentanyl group. In both groups, there was a predominance of patients who were awake and either calm or sleepy.CONCLUSIONS: The addition of fentanyl and sufentanil to hyperbaric subarachnoid bupivacaine was shown to be effective for the performance of cesarean section, and safe for the mother and fetus. Analgesia was more prolonged with sufentanil.2911752758Dahlgren, G., Hultstrand, C., Jakobsson, J., Norman, M., Eriksson, E.W., Martin, H., Intrathecal sufentanil, fentanyl, or placebo added to bupivacaine for cesarean section (1997) Anesth Analg, 85 (6), pp. 1288-1293. , Dec, PMID: 9390596Dyer, R.A., Joubert, I.A., Low-dose spinal anaesthesia for Caesarean section (2004) Curr Opin Anaesthesiol, 17 (4), pp. 301-308. , 2004 Aug, PMID: 17021569Arzola, C., Wieczorek, P.M., Efficacy of low-dose bupivacaine in spinal anaesthesia for Caesarean delivery: Systematic review and meta-analysis (2011) Br J Anaesth, 107 (3), pp. 308-318. , Sep, Epub 2011 Jul 14Braga Ade, F., Frias, J.A., Braga, F.S., Pereira, R.I., Titotto, S.M., Spinal anesthesia for elective ceasarean section: Use of different doses of hyperbaric bupivacaine associated with morphine and clonidine (2013) Acta Cir Bras, 28 (1), pp. 26-32. , Jan, PMID: 23338110Braga Ade, F., Braga, F.S., Potério, G.M., Pereira, R.I., Reis, E., Cremonesi, E., Sufentanil added to hyperbaric bupivacaine for subarachnoid block in Caesarean section (2003) Eur J Anaesthesiol, 20 (8), pp. 631-635. , Aug, PMID: 12932064Braga Ade, F., Frias, J.A., Braga, F.S., Pinto, D.R., Spinal block with 10 mg of hyperbaric bupivacaine associated with 5 microg of sufentanil for cesarean section. 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A case report (1988) Br J Anaesth, 60 (5), pp. 592-594. , Apr, PMID: 3377935Chu, C.C., Shu, S.S., Lin, S.M., Chu, N.W., Leu, Y.K., Tsai, S.K., Lee, T.Y., The effect of intrathecal bupivacaine with combined fentanyl in cesarean section (1995) Acta Anaesthesiol Sin, 33 (3), pp. 149-154. , Sep, PMID: 7493145Belzarena, S.D., Clinical effects of intrathecally administered fentanyl in patients undergoing cesarean section (1992) Anaesth Analg, 74 (5), pp. 653-657. , May, PMID: 1567031Idowu, O.A., Sanusi, A.A., Eyelade, O.R., Effects of intrathecally administered fentanyl on duration of analgesia in patients undergoing spinal anaesthesia for elective caesarean section (2011) Afr J Med Med Sci, 40 (3), pp. 213-219. , Sep, PMID: 22428515Hunt, C.O., Naulty, J.S., Bader, A.M., Hauch, M.A., Vartikar, J.V., Datta, S., Hertwig, L.M., Ostheimer, G.W., Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery (1989) Anesthesiology, 71 (4), pp. 535-540. , Oct, PMID: 2679237Sibilla, C., Albertazz, P., Zatelli, R., Martinello, R., Perioperative analgesia for caesarean section: Comparison of intrathecal morphine and fentanyl alone or in combination (1997) Int J Obstet Anesth, 6 (1), pp. 43-48. , Jan, PMID: 15321310Courtney, M.A., Bader, A.M., Hartwell, B., Hauch, M., Grennan, M.J., Datta, S., Perioperative analgesia with subarachnoid sufentanil administration (1992) Reg Anesth, 17 (5), pp. 274-278. , Sep-Oct, PMID: 1419940Akkamahadevi, P., Srinivas, H., Siddesh, A., Kadli, N., Comparision of efficacy of sufentanil and fentanyl with low-concentration bupivacaine for combined spinal epidural labour analgesia (2012) Indian J Anaesth, 56 (4), pp. 365-369. , JulLee, J.H., Chung, K.H., Lee, J.Y., Chun, D.H., Yang, H.J., Ko, T.K., Yun, W.S., Comparison of fentanyl and sufentanil added to 0.5% hyperbaric bupivacaine for spinal anesthesia in patients undergoing cesarean section (2011) Korean J Anesthesiol, 60 (2), pp. 103-108. , FebBang, Y.S., Chung, K.H., Lee, J.H., Hong, S.K., Choi, S.H., Lee, J.Y., Lee, S.Y., Yang, H.J., Comparison of clinical effects according to the dosage of sufentanil added to 0.5% hyperbaric bupivacaine for spinal anesthesia in patients undergoing cesarean section (2012) Korean J Anesthesiol, 63 (4), pp. 321-326. , OctNelson, K.E., Rauch, T., Terebuh, V., D’angelo, R., A comparison of intrathecal fentanyl and sufentanil for labor analgesia (2002) Anesthesiology, 96 (5), pp. 1070-1073. , May, PMID: 11981144Grass, J.A., Sakima, N.T., Schmidt, R., Michitsch, R., Zuckerman, R.L., Harris, A.P., A randomized, double-blind, dose-response comparison of epidural fentanyl versus sufentanil analgesia after cesarean section (1997) Anesth Analg, 85 (2), pp. 365-371. , Aug, PMID: 9249115Vyas, N., Sahu, D.K., Parampill, R., Comparative study of intrathecal sufentanil bupivacaine versus intrathecal bupivacaine in patients undergoing elective cesarean section (2010) J Anaesthesiol Clin Pharmacol, 26 (4), pp. 488-492. , Oct, PMID: 21547176Trivedi, V., Jha, A., A comparative clinical study of intrathecal fentanyl v/s sufentanil with bupivacaine for postoperative analgesia in emergency or elective cesarean section (2008) Indian J Pain, 22, pp. 157-162Dahl, J.B., Jeppesen, I.S., Jørgensen, H., Wetterslev, J., Møiniche, S., Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: A qualitative and quantitative systematic review of randomized controlled trials (1999) Anesthesiology, 91 (6), pp. 1919-1927. , Dec, PMID: 10598635Kjellberg, F., Tramèr, M.R., Pharmacological control of opioid-induced pruritus: A quantitative systematic review of randomized trials (2001) Eur J Anaesthesiol, 18 (6), pp. 346-357. , Jun, PMID: 11412287Scott, P.V., Fischer, H.B., Spinal opiate analgesia and facial pruritus: A neural theory (1982) Postgrad Med J, 58 (683), pp. 531-535. , Sep, PMID: 6755416Szarvas, S., Harmon, D., Murphy, D., Neuraxial opioid-induced pruritus: A review (2003) J Clin Anesth, 15 (3), pp. 234-239. , May, PMID: 1277066

QED3 theory of underdoped high temperature superconductors

Low-energy theory of d-wave quasiparticles coupled to fluctuating vortex loops that describes the loss of phase coherence in a two dimensional d-wave superconductor at T=0 is derived. The theory has the form of 2+1 dimensional quantum electrodynamics (QED3), and is proposed as an effective description of the T=0 superconductor-insulator transition in underdoped cuprates. The coupling constant ("charge") in this theory is proportional to the dual order parameter of the XY model, which is assumed to be describing the quantum fluctuations of the phase of the superconducting order parameter. The principal result is that the destruction of phase coherence in d-wave superconductors typically, and immediately, leads to antiferromagnetism. The transition can be understood in terms of the spontaneous breaking of an approximate "chiral" SU(2) symmetry, which may be discerned at low enough energies in the standard d-wave superconductor. The mechanism of the symmetry breaking is analogous to the dynamical mass generation in the QED3, with the "mass" here being proportional to staggered magnetization. Other insulating phases that break chiral symmetry include the translationally invariant "d+ip" and "d+is" insulators, and various one dimensional charge-density and spin-density waves. The theory offers an explanation for the rounded d-wave-like dispersion seen in ARPES experiments on Ca2CuO2Cl2 (F. Ronning et. al., Science 282, 2067 (1998)).Comment: Revtex, 20 pages, 5 figures; this is a much extended follow-up to the Phys. Rev. Lett. vol.88, 047006 (2002) (cond-mat/0110188); improved presentation, many additional explanations, comments, and references added, sec. IV rewritten. Final version, to appear in Phys. Rev.