Preparation of Biocompatible Carboxymethyl Chitosan Nanoparticles for Delivery of Antibiotic Drug.

Preparation of biocompatible carboxymethyl chitosan nanoparticles for delivery of antibiotic drug.

Biomed Res Int. 2013; 2013: 236469
Zhao L, Zhu B, Jia Y, Hou W, Su C

Objective. To prepare biocompatible ciprofloxacin-loaded carboxymethyl chitosan nanoparticles (CCC NPs) and evaluate their cell specificity as well as antibacterial activity against Escherichia coli in vitro. Methods. CCC NPs were prepared by ionic cross-linking method and optimized by using Box-Behnken response surface method (BBRSM). Zeta potential, drug encapsulation, and release of the obtained nanoparticles in vitro were thoroughly investigated. Minimum inhibitory concentration (MIC) and killing profiles of free or ciprofloxacin-loaded nanoparticles against Escherichia coli were documented. The cytotoicity of blank nanoparticles and cellular uptake of CCC NPs were also investigated. Results. The obtained particles were monodisperse nanospheres with an average hydrated diameter of 151?±?5.67?nm and surface of charge -22.9?±?2.21?mV. The MICs of free ciprofloxacin and CCC NPs were 0.16 and 0.08??g/mL, respectively. Blank nanoparticles showed no obvious cell inhibition within 24?h, and noticeable phagocytosis effect was observed in the presence of CCC NPs. Conclusion. This study shows that CCC NPs have stronger antibacterial activity against Escherichia coli than the free ciprofloxacin because they can easily be uptaken by cells. The obtained CCC NPs have promising prospect in drug delivery field. HubMed – drug


Net present value approaches for drug discovery.

Springerplus. 2013 Dec; 2(1): 140
Svennebring AM, Wikberg JE

Three dedicated approaches to the calculation of the risk-adjusted net present value (rNPV) in drug discovery projects under different assumptions are suggested. The probability of finding a candidate drug suitable for clinical development and the time to the initiation of the clinical development is assumed to be flexible in contrast to the previously used models. The rNPV of the post-discovery cash flows is calculated as the probability weighted average of the rNPV at each potential time of initiation of clinical development. Practical considerations how to set probability rates, in particular during the initiation and termination of a project is discussed. HubMed – drug


The cost effectiveness of pandemic influenza interventions: a pandemic severity based analysis.

PLoS One. 2013; 8(4): e61504
Milne GJ, Halder N, Kelso JK

The impact of a newly emerged influenza pandemic will depend on its transmissibility and severity. Understanding how these pandemic features impact on the effectiveness and cost effectiveness of alternative intervention strategies is important for pandemic planning.A cost effectiveness analysis of a comprehensive range of social distancing and antiviral drug strategies intended to mitigate a future pandemic was conducted using a simulation model of a community of ?30,000 in Australia. Six pandemic severity categories were defined based on case fatality ratio (CFR), using data from the 2009/2010 pandemic to relate hospitalisation rates to CFR.Intervention strategies combining school closure with antiviral treatment and prophylaxis are the most cost effective strategies in terms of cost per life year saved (LYS) for all severity categories. The cost component in the cost per LYS ratio varies depending on pandemic severity: for a severe pandemic (CFR of 2.5%) the cost is ?$ 9 k per LYS; for a low severity pandemic (CFR of 0.1%) this strategy costs ?$ 58 k per LYS; for a pandemic with very low severity similar to the 2009 pandemic (CFR of 0.03%) the cost is ?$ 155 per LYS. With high severity pandemics (CFR >0.75%) the most effective attack rate reduction strategies are also the most cost effective. During low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, while for high severity pandemics costs are dominated by hospitalisation costs and productivity losses due to death.The most cost effective strategies for mitigating an influenza pandemic involve combining sustained social distancing with the use of antiviral agents. For low severity pandemics the most cost effective strategies involve antiviral treatment, prophylaxis and short durations of school closure; while these are cost effective they are less effective than other strategies in reducing the infection rate. HubMed – drug


Verbal Memory Deficits Are Correlated with Prefrontal Hypometabolism in (18)FDG PET of Recreational MDMA Users.

PLoS One. 2013; 8(4): e61234
Bosch OG, Wagner M, Jessen F, Kühn KU, Joe A, Seifritz E, Maier W, Biersack HJ, Quednow BB

3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users.Brain glucose metabolism in rest was assessed using 2-deoxy-2-((18)F)fluoro-D-glucose positron emission tomography ((18)FDG PET) in 19 male recreational users of MDMA and 19 male drug-naïve controls. (18)FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test.As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei) of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex.Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users arise from combined fronto-parieto-mediotemporal dysfunction. HubMed – drug


Pattern of Drug Use and Depressive Symptoms among Amphetamine Type Stimulants Users in Beijing and Guangdong Province, China.

PLoS One. 2013; 8(4): e60544
Bao YP, Qiu Y, Yan SY, Jia ZJ, Li SX, Lian Z, Mu Y, Liu ZM

In recent years, amphetamine-type stimulants (ATS) have increased dramatically in East-south Asia, especially in China. Most ATS users suffered from psychosis comorbidity, and depression is the main syndrome in ATS users.A cross-sectional study of depressive symptoms and associated factors among ATS users was conducted in compulsory and voluntary drug detoxification and rehabilitation centers of Beijing and Guangdong Province from March, 2010 to August, 2010. Total 402 eligible participants were recruited and investigated by trained interviewers using a structured questionnaire, the depression was measured by the short 13-item Beck Depression Inventory (BDI-13). Multiple logistic regression was used to determine the impact of associated risk factors of depressive symptoms (%?8). PRINCIPLE FINDING: The mean score of BDI-13 is 8.11, and 169 participants (42.04%) have depressive symptoms, including 106 (26.37%) with moderate and 63 (15.67%) with severe depressive symptoms. Higher dose of ATS use, history of ATS relapse were associated with moderate and severe depressive symptoms, the adjusted odds ratios (OR) was 2.62, (95% CI: 1.45-4.74) and 2.01 (95% CI: 1.18-3.42) respectively. The cessation of 12 months or more had less risk of depressive symptoms than the current users, the OR was 0.46 (95% CI: 0.24-0.91), and the ATS users reporting nicotine dependence and alcohol drinking had significantly more risk of depressive symptoms for 3.11 (1.83-5.28) and 2.22 (1.35-3.65) times than those without these behaviors.Depressive symptoms co-occurred frequently among ATS users in China. The efforts that facilitate drug users’ attempts to stop using ATS use and relapse, quit cigarette smoking and stop alcohol drinking during the ATS treatment and management process should be supported as they may contribute to improving the mental health among this population. HubMed – drug