Stereoselective plasma protein binding of ibuprofen enantiomers

Summary We have developed a novel and reproducible method for determining the plasma protein binding of the two ibuprofen enantiomers in the presence of each other. The method involves the use of radiolabelled racemic ibuprofen, equilibrium dialysis, derivatization of the enantiomers to diastereomeric amides, high-performance liquid chromatography, and radiochemical analysis.We have determined the plasma protein binding of R(–)- and S(+)-ibuprofen in 6 healthy male volunteers after the oral administration of 800 mg racemic ibuprofen.The mean time-averaged percentage unbound of the R(–)-enantiomer, 0.419 was significantly less than that of the S(+)-enantiomer, 0.643, consistent with stereoselective plasma protein binding.The percentage unbound of each ibuprofen enantiomer was concentration-dependent over the therapeutic concentration range and was influenced by the presence of its optical antipode.     

The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents.     

Trial of an intervention to reduce chronic benzodiazepine use among residents of aged-care accommodation

Abstract Background: Many residents of aged-care accommodation are chronic users of benzodiazepines. This pattern of use contradicts current guidelines and may adversely affect residents. It was hypothesised that a lasting reduction in benzodiazepine use could be achieved through a programme which involved prescribers, residents and caregivers in the change process. Aim: To demonstrate that an intervention which involved education and relaxation training for patients, and education of prescribers and caregivers, could reduce levels of chronic benzodiazepine use among residents of an aged-care facility. Methods: Two aged-care facilities from metropolitan Adelaide were chosen; one received the intervention, the other was a no-intervention comparison. Pre-test, post-test and follow-up interviews were conducted with 60 residents: 27 from the intervention setting and 33 from the comparison setting. Residents at the intervention setting were provided with relaxation skills training, and their medical practitioners and caregivers were provided with information about alternative strategies for managing sleep disturbance. Outcome measures were: the proportion of residents using benzodiazepines, total medication use, cognitive performance, emotional responsiveness, subjective health and sleep ratings and an index of well-being. Results: The proportion of participants in the intervention condition who used benzodiazepines declined significantly (from 70% to 35%); the reduction was maintained over the subsequent three months. No adverse consequences were associated with cessation of benzodiazepine use; there was improvement in emotional responsiveness among those who ceased benzodiazepine use. This structured intervention strategy is a useful approach for reducing levels of chronic benzodiazepine use among residents of aged-care accommodation.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

The effects of anesthesia on the excretion of an isotonic saline load in the rat

The ability to excrete a volume of isotonic saline equal to 10% of body weight infused over 60 min, was examined in awake rats and in rats anesthetized with 1 of the 2 agents most commonly used in renal clearance studies, Inactin or Nembutal. Rats anesthetized with Inactin excreted significantly less of the infused sodium during the period of infusion and in the 120-min post-infusion periods as compared to Nembutal-anesthetized rats or awake rats. Following saline infusion, there was a significantly greater decrease in serum protein concentration (25.5±4.7%) in rats anesthetized with Inactin, compared to that observed in the awake or Nembutal-treated rats. In a separate group of saline-infused awake rats, induction of anesthesia with Inactin resulted in a significant increase in hematocrit and a decrease in serum protein concentration. These studies suggest that Inactin anesthesia decreases the ability of the kidney to excrete a saline load and that, in studies of sodium excretion in the rat, especially if volume expansion is to be part of the experimental protocol, Nembutal rather than Inactin may be the anesthetic of choice.These studies were performed while Drs. Knight and Frankfurt were Fellows in Nephrology of Baylor College of Medicine, and were supported in part by a Clinical Investigatorship award to Dr. Weinman and an Associate Investigatorship award to Dr. Frankfurt from the Veterans Administration. This work was presented in part at the Combined Session, Southern Section, American Federation for Clinical Research and the Southern Society for Clinical Investigation, New Orleans, Louisiana, January 27–29, 1977, and has appeared in abstract form in Clin. Res.25, 61 A (1977)