Imaging beta-adrenoceptors in the human brain with (S)-1'-[F-18]fluorocarazolol

We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[F-18]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pK(i) beta(1) 9.4, beta(2) 10.0, 5HT(1A) 7.4, 5HT(1B) 8.1) and rapidly crosses the blood-brain barrier. Methods: The (S)-[F-18]fluorocarazolol (74 MBq, >37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk, The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode. Results: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum, Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain, The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals. Conclusion: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease

Imaging beta-adrenoceptors in the human brain with (S)-1'-[F-18]fluorocarazolol

We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[F-18]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pK(i) beta(1) 9.4, beta(2) 10.0, 5HT(1A) 7.4, 5HT(1B) 8.1) and rapidly crosses the blood-brain barrier. Methods: The (S)-[F-18]fluorocarazolol (74 MBq, >37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk, The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode. Results: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum, Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain, The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals. Conclusion: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease

Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor density and electrical activation pattern in a rabbit model of non-ischemic heart failure

BACKGROUND: Since only little is known on stem cell therapy in non-ischemic heart failure we wanted to know whether a long-term improvement of cardiac function in non-ischemic heart failure can be achieved by stem cell transplantation. METHODS: White male New Zealand rabbits were treated with doxorubicine (3 mg/kg/week; 6 weeks) to induce dilative non-ischemic cardiomyopathy. Thereafter, we obtained autologous bone marrow stem cells (BMSC) and injected 1.5–2.0 Mio cells in 1 ml medium by infiltrating the myocardium via a left anterolateral thoracotomy in comparison to sham-operated rabbits. 4 weeks later intracardiac contractility was determined in-vivo using a Millar catheter. Thereafter, the heart was excised and processed for radioligand binding assays to detect β(1)- and β(2)-adrenoceptor density. In addition, catecholamine plasma levels were determined via HPLC. In a subgroup we investigated cardiac electrophysiology by use of 256 channel mapping. RESULTS: In doxorubicine-treated animals β-adrenoceptor density was significantly down-regulated in left ventricle and septum, but not in right ventricle, thereby indicating a typical left ventricular heart failure. Sham-operated rabbits exhibited the same down-regulation. In contrast, BMSC transplantation led to significantly less β-adrenoceptor down-regulation in septum and left ventricle. Cardiac contractility was significantly decreased in heart failure and sham-operated rabbits, but was significantly higher in BMSC-transplanted hearts. Norepinephrine and epinephrine plasma levels were enhanced in heart failure and sham-operated animals, while these were not different from normal in BMSC-transplanted animals. Electrophysiological mapping revealed unaltered electrophysiology and did not show signs of arrhythmogeneity. CONCLUSION: BMSC transplantation improves sympathoadrenal dysregualtion in non-ischemic heart failure

Optical pump rectification emission: route to terahertz free-standing surface potential diagnostics

We introduce a method for diagnosing the electric surface potential of a semiconductor based on THz surface generation. In our scheme, that we name Optical Pump Rectification Emission, a THz field is generated directly on the surface via surface optical rectification of an ultrashort pulse after which the DC surface potential is screened with a second optical pump pulse. As the THz generation directly relates to the surface potential arising from the surface states, we can then observe the temporal dynamics of the static surface field induced by the screening effect of the photo-carriers. Such an approach is potentially insensitive to bulk carrier dynamics and does not require special illumination geometries

Similarities and differences in the autonomic control of airway and urinary bladder smooth muscle

The airways and the urinary bladder are both hollow organs serving very different functions, i.e. air flow and urine storage, respectively. While the autonomic nervous system seems to play only a minor if any role in the physiological regulation of airway tone during normal breathing, it is important in the physiological regulation of bladder smooth muscle contraction and relaxation. While both tissues share a greater expression of M2 than of M3 muscarinic receptors, smooth muscle contraction in both is largely mediated by the smaller M3 population apparently involving phospholipase C activation to only a minor if any extent. While smooth muscle in both tissues can be relaxed by β-adrenoceptor stimulation, this primarily involves β2-adrenoceptors in human airways and β3-adrenoceptors in human bladder. Despite activation of adenylyl cyclase by either subtype, cyclic adenosine monophosphate plays only a minor role in bladder relaxation by β-agonists; an important but not exclusive function is known in airway relaxation. While airway β2-adrenoceptors are sensitive to agonist-induced desensitization, β3-adrenoceptors are generally considered to exhibit much less if any sensitivity to desensitization. Gene polymorphisms exist in the genes of both β2- and β3-adrenoceptors. Despite being not fully conclusive, the available data suggest some role of β2-adrenoceptor polymorphisms in airway function and its treatment by receptor agonists, whereas the available data on β3-adrenoceptor polymorphisms and bladder function are too limited to allow robust interpretation. We conclude that the distinct functions of airways and urinary bladder are reflected in a differential regulation by the autonomic nervous system. Studying these differences may be informative for a better understanding of each tissue