Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated <it>Plasmodium falciparum </it>malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the <it>in vivo </it>efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam^®, Mephaquin^®, and Mefloquina-AC^®Farma) given in combination with artesunate.</p> <p>Methods</p> <p>Thirty-nine non-pregnant adults with <it>P. falciparum </it>mono-infection were randomly assigned to receive artesunate in combination with either (1) Lariam, (2) Mephaquin, or (3) Mefloquina AC. Patients were assessed on Day 0 (with blood samples for pharmacokinetics at 0, 2, 4, and 8 hours), 1, 2, 3, 7, and then weekly until day 56. Clinical and parasitological outcomes were based on the standardized WHO protocol.</p> <p>Whole blood mefloquine concentrations were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined using non-compartmental analysis of concentration versus time data.</p> <p>Results</p> <p>By day 3, all patients had cleared parasitaemia except for one patient in the AC Farma arm; this patient cleared by day 4. No recurrences of parasitaemia were seen in any of the 34 patients. All three MQ formulations had a terminal half-life of 14–15 days and time to maximum plasma concentration of 45–52 hours. The maximal concentration (C_max) and interquartile range was 2,820 ng/ml (2,614–3,108) for Lariam, 2,500 ng/ml (2,363–2,713) for Mephaquin, and 2,750 ng/ml (2,550–3,000) for Mefloquina AC Farma. The pharmacokinetics of the three formulations were generally similar, with the exception of the C_maxof Mephaquin which was significantly different to that of Lariam (<it>p </it>= 0.04).</p> <p>Conclusion</p> <p>All three formulations had similar pharmacokinetics; in addition, the pharmacokinetics seen in this Peruvian population were similar to reports from other ethnic groups. All patients rapidly cleared their parasitaemia with no evidence of recrudescence by Day 56. Continued surveillance is needed to ensure that patients continue to receive optimal therapy.</p

Detection of Batrachochytrium dendrobatidis in amphibians imported into the UK for the pet trade

There is increasing evidence that the global spread of the fungal pathogen Batrachochytrium dendrobatidis (Bd) has been facilitated by the international trade in amphibians. Bd was first detected in the UK in 2004, and has since been detected in multiple wild amphibian populations. Most amphibians imported into the UK for the pet trade from outside the European Union enter the country via Heathrow Animal Reception Centre (HARC), where Bd positive animals have been previously detected. Data on the volume, diversity and origin of imported amphibians were collected for 59 consignments arriving at HARC between November 2009 and June 2012, along with a surveillance study to investigate the prevalence of Bd in these animals. Forty three amphibian genera were recorded, originating from 12 countries. It was estimated that 5000 – 7000 amphibians are imported through HARC into the UK annually for the pet trade. Bd was detected in consignments from the USA and Tanzania, in six genera, resulting in an overall prevalence of 3.6%. This suggests that imported amphibians are a source of Bd within the international pet trade

Support for people who use Anabolic Androgenic Steroids: A Systematic Scoping Review into what they want and what they access.

BACKGROUND: Since there is a paucity of research on support for people using Anabolic Androgenic Steroids (AAS), we aimed to identify and synthesise the available evidence in this field. Gaining an understanding of the support both accessed and wanted by recreational AAS users will be of use to professionals who provide services to intravenous substance users and also to those working in the fields of public health and social care, with the aim to increase engagement of those using AAS. METHODS: A systematic scoping review of the literature to explore and identify the nature and scope of information and support both accessed and wanted by non-prescribed AAS users. Any support services or information designed to help people who use AAS were considered. RESULTS: We identified 23 papers and one report for review, which indicated that AAS users access a range of sources of information on: how to inject, substance effectiveness, dosages and side effects, suggesting this is the type of information users want. AAS users sought support from a range of sources including medical professionals, needle and syringe programmes, friends, dealers, and via the internet, suggesting that, different sources were used dependent on the information or support sought. DISCUSSION: AAS users tended to prefer peer advice and support over that of professionals, and access information online via specialist forums, reflecting the stigma that is experienced by AAS users. These tendencies can act as barriers to accessing services provided by professionals. CONCLUSIONS: Support needs to be specific and targeted towards AAS users. Sensitivity to their perceptions of their drug-use and the associated stigma of being classified in the same sub-set as other illicit drug users is relevant to facilitating successful engagement

The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin–positive interneurons

The aim of this study was to evaluate the behavioral effects of chronic (six weeks) nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose) administration (in order to mimic heavy human abuse), and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break), applied alone and simultaneously with ND, in male rats (n = 40). Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV) content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF) test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone) and in elevated plus maze (EPM) test (decrease in frequency and cumulative duration in open arms, and total exploratory activity), that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region), followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters), and in evoked beam-walking test (increase in time to cross the beam), compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system) may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols