PubMed · 13095479
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F GIALDI, R PONCI. 1953. [Tablets for sublingual use].. https://pubmed.ncbi.nlm.nih.gov/13095479/
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Introducing Drosophila models in neuropharmacological research helps to discover new mechanisms of drug action. In fruit flies, the pharmacobehavioral approach has been used to evaluate the effects of drugs of abuse including cocaine. Standard procedures of cocaine administration to flies employ drug vaporization whereas behavior is evaluated either by trained observers or by videotaping followed by analysis via a computer-operated tracking system. Because in mammalian studies cocaine is typically administered by injection, a procedure that ensures precise and timely dose delivery, we developed a method for injecting cocaine into adult Drosophila. To objectively measure the behavioral response of flies to cocaine injections, we adapted the standard Drosophila Activity Monitoring System (Trikinetics). We found that in wild-type Canton S flies, cocaine injections produce a dose-dependent increase in the number of hyperactivity bursts and that repeated injections of cocaine produce behavioral sensitization. Acute responses to cocaine were observed also in period null (per(0)) mutant flies, but in these flies, repeated injections of cocaine did not produce sensitization. In conclusion, we developed a method for accurately measuring the behavioral effects of cocaine in adult fruit flies that can be applied to studies of the mechanisms of behavioral sensitization.
OBJECTIVES: We set out to determine the effect of sublingual nitroglycerin (NTG), as used during routine tilt testing in patients with unexplained syncope, on hemodynamic characteristics and baroreflex control of heart rate (HR) and systemic vascular resistance (SVR). BACKGROUND: Nitroglycerin is used in tilt testing to elicit a vasovagal response. It is known to induce venous dilation and enhance pooling. Also, NTG is lipophilic and readily passes cell membranes, and animal studies suggest a sympatho-inhibitory effect of NTG on circulatory control. METHODS: Routine tilt testing was conducted in 39 patients with suspected vasovagal syncope (age 36 +/- 16 years, 18 females). Patients were otherwise healthy and free of medication. Before a loss of consciousness set in, oncoming syncope was cut short by tilt-back or counter-maneuvers. Finger arterial pressure was monitored continuously (Finapres). Left ventricular stroke volume (SV) was computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of HR was estimated in the time and frequency domains. RESULTS: During tilt testing, 22 patients developed presyncope. After NTG administration but before presyncope, SV and cardiac output (CO) decreased (p < 0.001), whereas SVR and HR increased (p < 0.001) in all patients. Arterial pressure was initially maintained. Baroreflex sensitivity decreased after NTG. On Cox regression analysis, the occurrence of a vasovagal response was related to a drop in SV after NTG (hazard ratio 0.86, p = 0.005). CONCLUSIONS: The cardiovascular response to NTG is similar in vasovagal and non-vasovagal patients, but more pronounced in those with tilt-positive results. The NTG-facilitated presyncope appears to be CO-mediated, and there is no evidence of NTG-induced sympathetic inhibition.
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