Cyclosporin A in Fat Emulsion Carriers: Experimental Studies on Pharmacokinetics and Tissue Distribution

Abstract: In the commercially available intravenous formulation of Cyclosporin A (Sandimmun®), polyoxyethylated castor oil (Cremophor®EL) is used as a solubilizing agent. We have recently reported that the acute nephrotoxic effect of this preparation was alleviated by replacing Cremophor®EL with a soybean oil-based fat emulsion in a rat model. To further explore the potential of fat emulsions as carriers for cyclosporin A, data on the in vivo pharmacokinetics and tissue distribution are required. In this study in pigs, the pharmacokinetics of soybean oil-cyclosporin A was compared to that of Sandimmun®. The two formulations seemed bioequivalent, as there were no significant differences in the systemic clearances, volumes of distribution or elimination half-lives. Moreover, the tissue distributions of soybean oil-cyclosporin A and Sandimmun® were compared in rats. These studies also included two additional lipid-based carriers: one based on iodized ester of poppy seed oil and the other on a liposomal preparation. The tissue distributions were found to be similar regardless of the carriers used. Fat emulsion carriers seem to offer possibilities for preparing better tolerated intravenous formulations of cyclosporin A while maintaining the same characteristics concerning pharmacokinetics and tissue distribution.     

葛根素的心血管系统药理作用及机理研究

纵观近年来对葛根素在心血管系统药理作用及机理研究方面的进展发现，葛根素对心血管系统具有抗心律失常、降血压、扩张冠状动脉、抗心肌缺血、抗过氧化、抗缺血-再灌注损伤、影响血液动力学和血小板聚集、保护血管等作用。其临床应用前景良好，其药效机制研究及临床应用有待更深一步的探究。     

Socio‐cultural practices of deciduous canine tooth bud removal among Maasai children

The removal of teeth amongst the Maasai is a traditional practice as part of an initiation or to make space for feeding in an event of diseases locking the jaw. Removal of deciduous canine tooth buds (DCB) among infants below 2 years has been reported in several studies to be common mainly amongst communities in East Africa, Ethiopia and Sudan. The main reason for the practice revolves around the belief that tooth buds or ‘maggots’ are false teeth, nylon or worms and are responsible for diarrhoea, vomiting, fever and growth retardation in children, amongst other illnesses. The main objective of this study was to assess the socio‐cultural factors which contribute to this practice. The main methods of data collected included Focus Group Discussions (FGD) with mothers of children in that age group and Traditional Birth Attendants (TBA). In‐depth interviews (IDI) were conducted with key informants versed with Maasai traditions whereas observations were done within the manyattas where participants live. Proceedings at both the FGD and the ID1 were recorded on paper and were analysed thematically. The study showed that the removal of canine tooth buds amongst children that started initially with calves ‐ that diseases that cause diarrhoea in calves were brought about by the canine tooth buds that were turning reddish in colour ‐ is deeply rooted and practised in the community despite sensitisation interventions mounted jointly by the University of Nairobi, Kenya Medical Research Institute and the Kenya Medical Training College, among others. This study discovered that canine tooth buds are associated with bad spirits that cause diarrhoea and vomiting and the belief that removing them is a sure way of providing a cure for all children's ailments.     

Successful treatment of oesophageal candidiasis by micafungin: a novel systemic antifungal agent

AIM: To determine the minimum effective dose and safety of micafungin in the treatment of HIV-related oesophageal candidiasis. METHOD: A total of 120 patients were enrolled in this open label study of the effects of daily 1 h infusions of micafungin on endoscopically proven fungal oesophagitis. Patients were randomly assigned to receive 12.5, 25, 50, 75 and 100 mg of micafungin daily. Response was evaluated clinically and endoscopically. RESULTS: The protocol defined minimum effective dose of micafungin was 12.5 mg. The percentage of patients experiencing clearing of physical signs and symptoms showed a dose-response relationship and reached 94.7% in the 100 mg dose group. All patients in the 50, 75 and 100 mg dose groups achieved an endoscopically verified improvement in oesophagitis. Adverse effects of micafungin were generally mild and not dose-related. No serious renal, hepatic or drug-related infusion reactions were encountered. CONCLUSION: Micafungin was found to be effective, well-tolerated and safe. The minimum effective dose was found to be 12.5 mg and a significant linear trend in the successful treatment of oesophageal candidiasis was observed across the doses used with 75 and 100 mg dose levels achieving high rates of clinical and endoscopic cure.     

Morphine and alternative opioids in cancer pain: the EAPC recommendations

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.     

Mental health first aid training for the Chinese community in Melbourne,Australia: effects on knowledge about and attitudes toward people with mental illness

Background  

The aim of this study was to investigate in members of the Chinese community in Melbourne the impact of Mental Health First Aid (MHFA) training on knowledge about mental disorders and on attitudes to people with mental illness. The hypotheses were that at the end of the training participants would have increased knowledge of mental disorders and related treatments, and decreased negative attitudes towards people with mental disorders.     

Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society.

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi-squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p< 0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates.