This study investigated the testicular changes in the rat induced by the nonspecific phosphodiesterase inhibitor, theophylline using magnetic resonance microscopy (MRM) and ubiquitin immunostaining techniques. In vivo T1- and T2-weighted images were acquired at 2 T under anesthesia. Increased signal observed in the theophylline-treated rats suggests that leakage of MRM contrast was occurring. In vivo MRM results indicate that day 16 testis displayed an increased T1-weighted water signal in the area of the seminiferous tubule that decreased by day 32. These findings were validated by histopathology, suggesting that in vivo MRM has the sensitivity to predict changes in testis and epididymal tissues. The participation of the ubiquitin system was investigated, using probes for various markers of the ubiquitin-proteasome pathway. MRM can be used to detect subtle changes in the vascular perfusion of organ systems, and the up-regulation/mobilization of ubiquitin-proteasome pathway may be one of the mechanisms used in theophylline-treated epididymis to remove damaged cells before storage in the cauda epididymis. The combined use of in vivo MRM and subsequent tissue or seminal analysis for the presence of ubiquitin in longitudinal studies may become an important biomarker for assessing testis toxicities drug studies.

Background and objective: In this randomized, double-blind study, we aimed to investigate the effect of aminophylline on recovery from sevoflurane.

Methods: One-hundred ASA I–II patients scheduled for elective surgery were randomly divided into two groups receiving either NaCl 0.9% (Group 1, n = 50) or aminophylline 5 mg kg−1 (Group 2, n = 50). All patients were premedicated with atropine 0.01 mg kg−1 and midazolam 0.06 mg kg−1 intramuscularly. Anaesthesia was induced with propofol 2 mg kg−1 for muscle relaxation, and atracurium 0.5 mg kg−1 was maintained with sevoflurane 2% in 50% oxygen and nitrous oxide. Further atracurium (0.1 mg kg−1 was given when needed. Aminophylline or saline was given after sevoflurane was discontinued. Heart rate, mean arterial pressure, peripheral oxygen saturation, the duration of anaesthesia and recovery times (eye opening, verbal response, extubation and successful performance of arithmetical calculations) were recorded.

Results: There were no statistically significant differences in mean arterial pressure, peripheral oxygen saturation and anaesthesia time between the two groups. Heart rate increased significantly (P < 0.05) after aminophylline and was also higher than in the placebo group. Recovery times were significantly shorter (P < 0.001) in the patients receiving aminophylline.

Conclusions: Aminophylline speeded recovery after sevoflurane anaesthesia and it may have some advantage in anaesthesia practice for patients.

An RNA aptamer containing a 15-nt binding site shows high affinity and specificity for the bronchodilator theophylline. A variety of base modifications or 2′ deoxyribose substitutions in binding-site residues were tested for theophylline-binding affinity and the results were compared with the previously determined three-dimensional structure of the RNA–theophylline complex. The RNA–theophylline complex contains a U6-A28-U23 base triple, and disruption of this A28-U23 Hoogsteen-pair by a 7-deaza, 2′-deoxy A28 mutant reduces theophylline binding >45-fold at 25 °C. U24 is part of a U-turn in the core of the RNA, and disruption of this U-turn motif by a 2′-deoxy substitution of U24 also reduces theophylline binding by >90-fold. Several mutations outside the “conserved core” of the RNA aptamer showed reduced binding affinity, and these effects could be rationalized by comparison with the three-dimensional structure of the complex. Divalent ions are absolutely required for high-affinity theophylline binding. High-affinity binding was observed with 5 mM Mg2+, Mn2+, or Co2+ ions, whereas little or no significant binding was observed for other divalent or lanthanide ions. A metal-binding site in the core of the complex was revealed by paramagnetic Mn2+-induced broadening of specific RNA resonances in the NMR spectra. When caffeine is added to the aptamer in tenfold excess, the NMR spectra show no evidence for binding in the conserved core and instead the drug stacks on the terminal helix. The lack of interaction between caffeine and the theophylline-binding site emphasizes the extreme molecular discrimination of this RNA aptamer.

The acute influence of therapeutic doses of theophylline on cerebral blood flow velocities during general anaesthesia induced either by halothane or isoflurane has not been elucidated previously. The aim of this study, was therefore to investigate these effects during steady state anaesthetic conditions in anaesthetized patients using transcranial Doppler sonography. Thirty-four Patients were investigated. Anaesthesia was maintained either with 1 MAC (minimum alveolar concentration) halothane (n=16) or 1 MAC isoflurane (n=18); FiO2: 40%; end-expiratory pCO2: normocapnia. Theophylline administration was performed before surgery by infusing 6 mg kg−1 over a period of 7.5 min. Measurements were recorded prior to theophylline administration, and immediately after 2 mg kg−1 (2.5 min), 4 mg kg−1 (5 min) and 6 mg kg−1 (7.5 min), as well as 5, 10, 15, 20, 30 and 45 min after theophylline administration. Recorded variables included blood pressure, heart rate, arterial oxygen saturation, end-expiratory pCO2, body temperatures, middle cerebral artery blood flow velocity and pulsatility index. Theophylline administration was well tolerated by all study subjects. Heart rate, blood pressure, body temperatures, arterial oxygen saturation and end-expiratory pCO2 remained constant during the whole examination period. Following theophylline, mean blood flow velocity decreased by 25% in the halothane and by 30% in the isoflurane group (P< 0.05). By the end of the examination period, mean blood flow velocity had not yet recovered to the initial values whereby in both groups the mean blood flow velocity was 26% below the initial values. In the isoflurane group, the pulsatility index increased by about 20% (P< 0.05) and remained high until the end of the examination. In the halothane group, however, there were no changes in the pulsatility index. Our results show a remarkable, significant and simultaneous decrease in blood flow velocity in the middle cerebral artery associated with theophylline administration during halothane and isoflurane anaesthesia in man.