A reasonably accurate estimate of the relative physiological value of natural and of synthetic ar-tocopherols is needed by the clinician, the pharmaceutical industry, and the experimental nutritionist to facilitate their use of vitamin E in a more quantitative manner. At present there is preliminary information available for two species of animals. It was tentatively established (1) in 1944 tha...

The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In th...

Single morphine injections induce a state of acute opioid dependence measured by an increase in naloxone potency to precipitate withdrawal. Repeated morphine exposure (daily/weekly intervals) results in further potentiation of naloxone potency, perhaps due to conditioning mechanisms. The current study tested the hypothesis that previously neutral stimuli could elicit a conditioned potentiation ...

A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measur...

Opioid rotation is a strategy applied during opioid therapy for pain that refers to a switch from one opioid to another in an effort to improve clinical outcomes (benefits or harms). It begins with the selection of a new drug at a starting dose that minimizes potential risks while ideally maintaining analgesic efficacy. The selection of a starting dose must be informed by an estimate of the rel...

BACKGROUND Intrathecal anesthesia is commonly used for cesarean section. Bupivacaine and ropivacaine have all been used as intrathecal drugs. The minimum effective local anesthetic dose (MLAD) of intrathecal ropivacaine for non-obstetric patients has been reported. However, few data are available on the MLAD of hyperbaric ropivacaine for obstetric patients and the relative potency to bupivacain...

BACKGROUND Comparing the relative potency of new local anaesthetics such as levobupivacaine and ropivacaine with bupivacaine by the minimum local analgesic concentration model has not been described for neonatal spinal anaesthesia. This information is important to compare agents and to determine the most effective spinal dose. METHODS We performed a two-stage study to determine the ED50, the ...

We wish to use prior information on an existing drug in the design and analysis of a dose-response study for a new drug candidate within the same pharmacological class. Using the Bayesian methodology, this prior information can be used quantitatively and the randomization can be weighted in favor of the new compound, where there is less information. An Emax model is used to describe the dose-re...

Studies using dry powder devices have suggested that fluticasone propionate (FP) has a greater systemic effect than budesonide (BUD). The aim of the present study was to investigate and compare the relative systemic potency of FP and BUD from their respective pressurized metered-dose inhalers (pMDIs). A placebo-controlled, open, randomized, cross-over study was conducted in 21 healthy male volu...