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Article Abstract

Rationale: Although nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions.

Objectives: To determine the feasibility of a pulsed-nicotine infusion model in smokers.

Methods: Following overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1) high/fast: 1.0 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2) high/slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; (3) low/fast: 0.2 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4) low/slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and (5) placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session.

Results: Both the high/fast and high/slow conditions were associated with greater "head rush" and "high" (p < 0.05). The high/fast condition also provided greater suppression of urges to smoke and nicotine withdrawal (p < 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. The high/fast and high/slow conditions produced greater increases in heart rate (p < 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test.

Conclusions: These findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches.

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http://dx.doi.org/10.1007/s00213-022-06162-0DOI Listing

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Article Synopsis
  • The study aimed to assess the feasibility of a pulsed-nicotine infusion model in smokers, contrasting it with regular cigarette consumption.
  • Participants, after abstaining from cigarettes overnight, experienced various infusion conditions (high/fast, high/slow, low/fast, low/slow, and placebo) to evaluate the effects on their craving and cognitive performance.
  • Results indicated that higher doses delivered quickly or slowly reduced smoking urges and withdrawal symptoms more effectively, while also increasing heart rate, suggesting that this model can be helpful for future smoking cessation research.
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Background: When women require induction of labour, oxytocin is the most common agent used, delivered by an intravenous infusion titrated to uterine contraction strength and frequency. There is debate over the optimum dose regimen and how it impacts on maternal and fetal outcomes, particularly induction to birth interval, mode of birth, and rates of hyperstimulation. Current induction of labour regimens include both high- and low-dose regimens and are delivered by either continuous or pulsed infusions, with both linear and non-linear incremental increases in oxytocin dose.

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Object: Although pulsatile and continuous infusion paradigms have been described for convective delivery of drugs, the effectiveness and properties of each flow paradigm are unknown. To determine the effectiveness and properties of pulsatile and continuous convective infusion paradigms, the authors compared these convective flow methods in the gray and white matter of primates.

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An in vitro flow model to study streaming during pelvic intra-arterial drug infusions.

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Regional delivery of suitable drugs by intra-arterial infusion may offer a therapeutic advantage. High concentrations in the tumor are sought with reduced systemic toxicity. Adequate mixing of drug solutions with perfusing blood is essential to provide uniform distribution of drug to tumor-bearing tissue distal to the infusion site.

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To simulate the intra-arterial infusion of chemotherapy, ink was infused at a steady rate through a vascular catheter inserted in a transparent tube carrying water at a rate similar to that of arterial blood. The ink ran in one or two discrete streams for 10 to 15 cm before mixing with the water, and there were substantial differences in the concentrations of ink in the water collected from side holes made at various distances from the catheter tip. If the ink was delivered in short pulses, however, it mixed with the water 2 to 3 cm beyond the catheter tip, and the samples collected from the side holes showed similar concentrations of ink.

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