Medicine or ecstasy? The importance of the logo

Some pharmaceutical tablets have an appearance that resembles that of ecstasy (a logo and often a name referring to it, a given shape and/or a colour). These are sometimes sold in the street as ‘ecstasy’. In order to assess the knowledge of this phenomenon, surveys were conducted among designer drug users (DDUsers), pharmacists and pharmaceutical firms. Three surveys were conducted: the first one was conducted among DDUsers by means of an anonymous questionnaire; the second one consisted of a 1‐month postal survey within a network of 155 community pharmacies in the Aquitaine region, Southwestern France and the third one consisted of a postal questionnaire sent to 71 pharmaceutical firms. Nineteen users, 77 pharmacists and 25 pharmaceutical firms participated in the surveys. All DDUsers knew the existence of what they call ecstasy ‘swindles’, but less than one quarter of the pharmacists and one third of pharmaceutical firms were aware of the potential recreational and involuntary misuse of medicines. The phenomenon of ‘swindle’ in the illicit market is not new. However, the sale of medicines because of their appearance or logo seems to be quite rare. In order to limit this diversion, prevention should be reinforced. In addition, recommendations on the appearance of medicine tablets should be set up by regulatory agencies in charge of medicine approval.     

Post-operative C-reactive protein profile following abdominal wall reconstruction with transversus abdominis posterior components separation

IntroductionAbdominal wall reconstruction using posterior component separation with transversus abdominis release (AWTAR) produces a unique post-operative CRP profile, when compared to routine elective colorectal operations. Therefore, we aim to establish the normal post-operative C-reactive protein (poCRP) profile following AWRTAR and reduce the unnecessary invasive interventions in patients already at greater risk of septic complications.MethodsA retrospective analysis of daily poCRP levels was performed both for patients who underwent uncomplicated AWRTAR (n = 12), and a comparator group of uncomplicated open right hemicolectomies (RH) matched for age and sex (n = 24). All operations in both groups were performed by a single surgeon from 2013 to 2015.ResultsThe median (IQR) age was 62 (16) and 67 (16) years respectively, with a higher proportion of males to females in both groups (10:2 vs. 17:7). The poCRP profile follows an initial steep rise, peaking at day 2 followed by a gradual washout phase. The poCRP peak is significantly greater in the AWRTAR group compared to the RH group (274 [95%CI ±25] vs. 160 [95%CI ± 27]; p = 0.0001), with a positive correlation between day 2 CRP levels and operative length (r = 0.56).ConclusionsWe have demonstrated that uncomplicated AWRTAR provokes a significantly greater poCRP rise (>200) compared to that well described in the literature for uncomplicated open colectomy. As poCRP is an important marker of post-operative recovery with abnormally high levels associated with septic complications, these data should help clinicians interpret the post-operative clinical course after AWRTAR.     

Effects of fluoride tablets on caries and fluorosis occurrence among 6‐ to 9‐year olds using fluoridated salt

Meyer‐Lueckel H, Grundmann E, Stang A. Effects of fluoride tablets on caries and fluorosis occurrence among 6‐ to 9‐year olds using fluoridated salt. Community Dent Oral Epidemiol 2010; 38: 315–323. © 2010 John Wiley & Sons A/S Abstract – Objective: The aim of this retrospective cohort study was to investigate the association between the use of fluoride tablets among users of fluoridated salt and the occurrence of caries and fluorosis. Materials and methods: We examined 583 school children aged 6–9 years in Berlin, Germany for caries‐status (modified defs ≥ 1; d₃‐level) and fluorosis occurrence on central incisors (TSIF ≥ 1). Parents completed questionnaires about several sociodemographic and oral health related factors of the previous years. To adjust for confounding, we used log‐risk regression and estimated relative risks (RR) and 95% confidence intervals. Results: The mean modified defs was 3.2 (SD = 5.9) and 58% children were caries‐free. Twenty‐two per cent of the children revealed mild fluorosis (TSIF 1 and 2). Length of fluoride tablet use was inversely associated (adjusted for age and SES) with caries‐status: 2–4 years: RR = 0.8, 95%CI: 0.7–1.0, ≥5 years: RR = 0.5, 95%CI 0.3–0.7 (reference: 0–1 year use). This inverse association could mainly be observed in children who consumed fluoridated salt as well. Relative risks for mild fluorosis were 1.8 (95%CI: 1.1–2.9) and 2.7 (95%CI: 1.6–4.5) for fluoride tablet use of 2–4 years and ≥5 years, respectively compared with 0–1 year use. Conclusions: Fluoride tablets seem to be effective in reducing the occurrence of caries in children with low caries levels in particular among those using fluoridated salt as well. However, fluoride tablets increase the occurrence of mild fluorosis in permanent incisors.     

A modified cytotoxicity assay with high sensitivity

Since adoptive immunotherapy using lymphokine activated killer (LAK) cells and interleukin-2 (IL-2) has been introduced into clinical medicine, there has been a growing interest in cytotoxicity assays. The standard ⁵¹chromium release assay has certain disadvantages, in particular limited sensitivity, because of a high, nonspecific background release. We examined the conditions under which tritiated thymidine, which has been used to assess slow macrophage mediated cytolysis, can be utilized to assess the rapid cytotoxic activity of unstimulated PBL and LAK cells.

The optimal assay duration for the ³H-thymidine (³H-TdR) release assay is 24 h. Under standard conditions actively proliferating effector cells do incorporate some of the ³H-TdR released by the target cells during this time, leading to false low results. This problem can be abolished by the addition of excessive amounts of cold TdR to the assay medium. We found a good correlation of the results of the TdR release assay and the Cr release assay. Using the very sensitive TdR release assay, unexpected significant cytolysis of the so-called ‘NK resistant’ Daudi cells by unstimulated PBL is demonstrated. The modified ³H-TdR release assay is well-suited to monitor the immunological effects of immunotherapy, using IL-2 and LAK cells.     

Indirect treatment comparison of two non-invasive patient-controlled analgesia treatments for acute post-operative pain management

Objectives: To evaluate the relative clinical efficacy, safety, and tolerability associated with two non-invasive patient-controlled analgesia (PCA) treatments, sufentanil sublingual tablet system (SSTS) and fentanyl iontophoretic patient-controlled transdermal system (PCTS). These two treatments have recently been approved in the EU for the management of acute moderate-to-severe post-operative pain in adult patients.

Methods: As no head-to-head trials comparing SSTS and PCTS currently exist, indirect treatment comparison (ITC) analyses were conducted to evaluate SSTS or PCTS versus intravenous (IV) morphine PCA.

Results: Five studies, four assessing PCTS and one assessing SSTS, were included in this analysis. SSTS had statistical or numerical advantages over PCTS for both patient global assessment (PGA) and healthcare professional global assessment (HPGA) outcomes at all time points investigated. SSTS was also associated with greater patient ease of use (weighted mean difference [WMD]: 0.13; 95% confidence interval [CI]: ?0.02–0.28) and a higher patient satisfaction score (WMD: 0.31; 95% CI: 0.05–0.57; p?=?.019) compared with PCTS. In terms of tolerability, all-cause withdrawals from treatment were reported to be less likely with SSTS (risk ratio: 0.65; 95% CI: 0.42–1.02). No significant differences were observed between SSTS and PCTS in terms of safety and adverse events.

Conclusions: In the absence of direct head-to-head data, the combination of promising phase III trial results compared to IV morphine PCA, a SLR comparison against other opioid treatments, and the results of this exploratory analysis present a strong rationale in support of SSTS as a key option for management of post-operative pain.     

Release characteristics of polymethacrylate nanospheres containing coumarin-6

Sustained release nanospheres were prepared from the polymethacrylates Eudragit^r` S₁₀₀ and E₁₀₀ containing a water insoluble dye by a salting-out method. Coumarin-6 was used as a model for insoluble analgesics to ascertain uptake and release properties dependent on polymer characteristics and pH. Morphology and particle size were characterized by scanning electron microscopy (SEM). Particles were smooth, spherical and uniform with diameters ranging from 0.6–0.8 μm. Yield was 38% and 86% for E₁₀₀and S₁₀₀, respectively, and encapsulation of coumarin-6 efficiency was 58% and 75%, respectively. Coumarin-6 was stable within the polymer matrix at temperatures from -20$C to 45$C for 4 months. Release was most efficient from S₁₀₀ polymers in phosphate buffer at pH 7.4 and 8.0 reaching a maximum ～ 5 hours prior to samples at pH 7.0 and 9.0. Release was biphasic and concentration as a function of the square root of time produced linear data suggesting a Higuchi type diffusion from a polymer matrix. Release from E₁₀₀ was 65% lower than that from S₁₀₀ and was not solely dependent upon the ionization of polymer but most likely due to a combination of factors including buffer ionization.     

Prediction of oral disintegration time of fast disintegrating tablets using texture analyzer and computational optimization

One of the promising approaches to predict in vivo disintegration time of orally disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the method is able to provide good in vitro in vivo correlation (IVIVC) in the case of different tablets, it might be able to predict the oral disintegration time of similar products. However, there are many tablet parameters that influence the in vivo and the in vitro disintegration time of ODT products. Therefore, the measured in vitro and in vivo disintegration times can occasionally differ, even if they coincide in most cases of the investigated products and the in vivo disintegration times may also change if the aimed patient group is suffering from a special illness. If the method is no longer able to provide good IVIVC, then the modification of a single instrumental parameter may not be successful and the in vitro method must be re-set in a complex manner in order to provide satisfactory results. In the present experiment, an optimization process was developed based on texture analysis measurements using five different tablets in order to predict their in vivo disintegration times, and the optimized texture analysis method was evaluated using independent tablets.     

Graded synaptic transmission at the Caenorhabditis elegans neuromuscular junction

Most neurotransmission is mediated by action potentials, whereas sensory neurons propagate electrical signals passively and release neurotransmitter in a graded manner. Here, we demonstrate that Caenorhabditis elegans neuromuscular junctions release neurotransmitter in a graded fashion. When motor neurons were depolarized by light-activation of channelrhodopsin-2, the evoked postsynaptic current scaled with the strength of the stimulation. When motor neurons were hyperpolarized by light-activation of halorhodopsin, tonic release of synaptic vesicles was decreased. These data suggest that both evoked and tonic neurotransmitter release is graded in response to membrane potential. Acetylcholine synapses are depressed by high-frequency stimulation, in part due to desensitization of the nicotine-sensitve ACR-16 receptor. By contrast, GABA synapses facilitate before becoming depressed. Graded transmission and plasticity confer a broad dynamic range to these synapses. Graded release precisely transmits stimulation intensity, even hyperpolarizing inputs. Synaptic plasticity alters the balance of excitatory and inhibitory inputs into the muscle in a use-dependent manner.     

肝得治片质量标准研究

目的制订肝得治片的质量控制方法。方法采用高效液相色谱法测定：C18柱（5μm,4.6×250mm）;乙腈-0.4%磷酸溶液（25：75）为流动相;检测波长为280nm。结果黄芩苷在0.1352-1.3520μg间线性关系良好,r=0.9999;回收率为97.03%,RSD=1.63%。结论本方法重现性好,可用于该制剂的质量控制。