Dehydro-dermorphins

Dehydrophenylalanine having the Z-configuration (ΔPhe) and D-Phe were incorporated in positions 3 and/or 5 into dermorphin-(1–5)-peptide amide (H-Tyr-D-Ala-Phe-Gly-Tyr-NH₂) in order to study the effect of structure or configurational changes. On GPI preparation, whereas the activity of [L-Phe⁵]-pentapeptide was fourfold higher than parent peptide and comparable to that of dermorphin, the substitution of Phe³ by its D-enantiomer was barely tolerated. The pentapeptides containing ΔPhe in positions 3 and/or 5 displayed even lower potency: particularly the unsaturation at position 3 alone or at position 3 and 5 was very detrimental to μ activity.     

Do European GSM Mobile Cellular Phones Pose a Potential Risk to Pacemaker Patients?

BARBARO, V., et al .: Do European GSM Mobile Cellular Phones Pose a Potential Risk to Pacemaker Patients? A series of in vivo trials were carried out in order to verify whether the electromagnetic field radiated by GSM (Groupe Systemes Mobiles) mobile cellular phones might affect implanted pacemakers. Two European GSM phones of 2-watt power were tested and trials conducted on 101 pacemaker implanted outpatients attending day hospital for routine check-up, who volunteered for trials. Forty-three pacemaker models from 11 manufacturers were tested in all. When the sensing threshold of the pacemakers was set at a minimum and the antenna of the phone was in direct contact with the patient's chest, interference was detected for 26 implanted pacemakers. Specifically, pulse inhibition in 10 of 101 cases, ventricular triggering in 9 of 46 DDD-VDD pacemakers, and asynchronous pacing in 4 of 52 devices. Pulse inhibition was also observed combined with asynchronous pacing in 1 of 52 cases and with ventricular triggering in 2 of 46 cases. Minimum effect duration was ca. 3 seconds but in 6 cases effects continued as long as the interfering GSM signal was on. No permanent malfunctioning or changes in the programmed parameters were detected. Whenever interference was detected, trials were repeated to determine the maximum sensing threshold at which interference persisted (with the antenna in contact with the skin over the pacemaker). Then maximum distance between antenna and pacemaker at which interference occurred was determined at pacemaker maximum and minimum sensing threshold. Under our experimental conditions electromagnetic interference effects were detected at a maximum distance of 10 cm with the pacemaker programmed at its minimum sensing threshold. When the phone antenna was in direct contact with patient's skin over the implant, electromagnetic interference effects occurred at maximum ventricular and atrial sensing thresholds of 4 mV and 2.5 mV, respectively.     

Synthesis and biological activity of carboxyl terminally extended dermorphins

Dermorphinoyl(DMR)-glycine, DMR-sarcosine and DMR-glycyl-arginine have been prepared in order to examine the effect of C-terminal extension of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂) on opioid activity. On GPI preparation the addition of Gly, Sar, or Gly-Arg to the carboxyl terminus of dermorphinoic acid was detrimental to μ activity: dermorphinoyl-derivatives, in fact, retain only 5–20% of dermorphin potency. Following intracerebroventricular administration (tail-flick test), whereas the analgesic activities of compounds showed the trend dermorphin >DMR-Sar> DMR-Gly-Arg>DMR-Gly>morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR-Gly-Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively.     

Emergency Cardiac Pacing for Severe Bradycardia

ALTAMURA, G., ET AL.: Emergency Cardiac Pacing for Severe Bradycardia. Our study included the treatment of transcutaneous cardiac pacing (TCP) in 32 patients: (A) 19 patients were treated in the emergency area for complete symptomatic AV block before endocavitary pacing; (B) five patients were in asystole following DC shock or out-of-hospital cardiac arrest; and (C) eight patients were affected by bifascicular block undergoing emergency surgery and were treated in order to prevent complete AV block. Two transcutaneous stimulators were used. PaceAid-CRC model 50/52 with 20-msec pulse width; the electrodes were positioned on the V, ECG position and on the back. Results: in all but two patients, it was possible to obtain stable cardiac capture; in one patient arrived in hospital in asystole after prolonged cardiac arrest and in the other one was affected by complete AV block, TCP was ineffective. In groups A and B, TCP was maintained for a mean time of 15 minutes; in group C, TCP was tested in all patients, but performed in only one patient during surgery. Mean threshold was 81 mA. Stimulation was well tolerated in all but five patients. TCP is a reliable, noninvasive method that offers the possibility to initiate pacing within seconds and can be used by medical staff. In our opinion, it should be considered as the first choice emergency treatment of severe symptomatic bradycardia. In asystole, beneficial effects can be obtained only if TCP is performed early enough after the onset of arrhythmia.