Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP) : evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users

BACKGROUND: 2,4-Dinitrophenol (DNP) poses serious health-risks to humans. The aims of this three-stage multidisciplinary project were, for the first time, to assess the risks to the general public from fraudulent sale of or adulteration/contamination with DNP; and to investigate motives, reasons and risk-management among DNP-user bodybuilders and avid exercisers. METHODS: Using multiple search-engines and guidance for Internet research, online retailers and bodybuilding forums/blogs were systematically explored for availability of DNP, advice offered on DNP use and user profiles. Ninety-eight pre-workout and weight-loss supplements were purchased and analysed for DNP using liquid-chromatography-mass-spectrometry. Psychosocial variables were captured in an international sample of 35 DNP users (26.06 ± 6.10 years, 94.3 % male) with an anonymous, semi-qualitative self-reported survey. RESULTS: Although an industrial chemical, evidence from the Internet showed that DNP is sold 'as is', in capsules or tablets to suit human consumption, and is used 'uncut'. Analytical results confirmed that DNP is not on the supplement market disguised under fictitious supplement names, but infrequently was present as contaminant in some supplements (14/98) at low concentration (<100mcg/kg). Users make conscious and 'informed' decisions about DNP; are well-prepared for the side-effects and show nonchalant attitude toward self-experimentation with DNP. Steps are often taken to ensure that DNP is genuine. Personal experience with performance- and appearance enhancing substances appears to be a gateway to DNP. Advice on DNP and experiences are shared online. The significant discrepancy between the normative perception and the actual visibility suggests that DNP use is-contrary to the Internet accounts-a highly concealed and lonesome activity in real life. Positive experiences with the expected weight-loss prevail over the negative experiences from side effects (all but two users considered using DNP again) and help with using DNP safely is considered preferable over scare-tactics. CONCLUSION: Legislation banning DNP sale for human consumption protects the general public but DNP is sold 'as is' and used 'uncut' by determined users who are not dissuaded from experimenting with DNP based on health threats. Further research with stakeholders' active participation is imperative for targeted, proactive public health policies and harm-reduction measures for DNP, and other illicit supplements

RNA Interference and Single Particle Tracking Analysis of Hepatitis C Virus Endocytosis

Hepatitis C virus (HCV) enters hepatocytes following a complex set of receptor interactions, culminating in internalization via clathrin-mediated endocytosis. However, aside from receptors, little is known about the cellular molecular requirements for infectious HCV entry. Therefore, we analyzed a siRNA library that targets 140 cellular membrane trafficking genes to identify host genes required for infectious HCV production and HCV pseudoparticle entry. This approach identified 16 host cofactors of HCV entry that function primarily in clathrin-mediated endocytosis, including components of the clathrin endocytosis machinery, actin polymerization, receptor internalization and sorting, and endosomal acidification. We next developed single particle tracking analysis of highly infectious fluorescent HCV particles to examine the co-trafficking of HCV virions with cellular cofactors of endocytosis. We observe multiple, sequential interactions of HCV virions with the actin cytoskeleton, including retraction along filopodia, actin nucleation during internalization, and migration of internalized particles along actin stress fibers. HCV co-localizes with clathrin and the ubiquitin ligase c-Cbl prior to internalization. Entering HCV particles are associated with the receptor molecules CD81 and the tight junction protein, claudin-1; however, HCV-claudin-1 interactions were not restricted to Huh-7.5 cell-cell junctions. Surprisingly, HCV internalization generally occurred outside of Huh-7.5 cell-cell junctions, which may reflect the poorly polarized nature of current HCV cell culture models. Following internalization, HCV particles transport with GFP-Rab5a positive endosomes, which is consistent with trafficking to the early endosome. This study presents technical advances for imaging HCV entry, in addition to identifying new host cofactors of HCV infection, some of which may be antiviral targets

Health impact of smoking - an unforgiveable omission in a doctor's repertoire.

Thomas I Lemon Institute of Medical Education, Cardiff University, Cardiff, UKRahman et al1 should be thanked for their discussion-provoking paper investigating the smoking behavior of patients and staff in a hospital based in Melbourne, Australia. The authors hoped to gather epidemiological data surrounding smoking, information on dependence to nicotine, and attitudes toward both the health impact and quitting strategies of smokers.&nbsp;View original paper by Rahman et a

Scientific LetterHomemade heroin substitute causing hallucinations

Click on the link to view the Letter.Afr J Psychiatry 2013;16:

Scientific Letter: Homemade heroin substitute causing hallucinations

No AbstractsAfrican Journal of Psychiatry • November 2013, 16(6

Prescribing tests must have curriculum support

Rupali D Shah, Thomas I LemonSchool of Medicine, Cardiff University, University Hospital of Wales, Cardiff, WalesGordon, Catchpole and Baker1 have discussed and investigated a very interesting, currently relevant, subject in medical education; particularly with the introduction of the prescribing test for undergraduates trialled in the UK this year and set to become a fully-fledged part of the curriculum and assessment criteria for 2014 graduates.2 It would of course be of great interest to compare the themes discussed in this paper and see they how would compare to recent graduates in late 2014.View original paper by Gordon and colleagues

Relationship between interblink interval and dopamine

Thomas I Lemon, Rupali D ShahSchool of Medicine, Cardiff University, University Hospital of Wales, Cardiff, United KingdomAn interesting study recently reported by Johnston et al1 investigated the interblink interval between dry and normal eye subjects. The authors concluded that this interval was reduced in dry eyes in comparison with normal eyes, that there was a greater variability in interblink intervals in normal eyes, and that the parameters were useful for diagnosis of dry eye disease.1View original paper by Johnston and colleague

BAK additive influence on results

Rupali D Shah, Thomas I Lemon, Ashley Yarrow-JenkinsInstitute of Medical Education, Cardiff University, Cardiff, Wales, UKThis letter is in regards to Fukuda et al.1 We thank the authors for their informative contribution. The use of rabbit specimens was relevant to this study as previously alluded to by Wilhelmus, who concluded from his research that rabbit eyes were more susceptible to irritants than human eyes.2View original paper by Fukuda and colleagues