Adverse reactions to drugs: in vitro studies with isolated cells

Objective and design: Drug-induced adverse reactions can be allergic or pseudoallergic in nature, in this study the histamine releasing ability of 4 radiographic contrast media and 2 opioid analgesics was tested on a variety of mast cell containing cell suspensions.

Time-averaged velocity and turbulence intensity at the initial downstream flow from a six-bladed propeller

The current study investigated the time-averaged velocity and turbulence intensity at the initial downstream flow from a six-bladed ship propeller. The six-bladed propeller provided the rapid periodical pulses of thrust in one revolution due to the blades leading to a complex downstream jet. The six-bladed propeller is popular as a boat racing propeller, but the presentation of its flow structure was rarely found in the previous studies. In this study, the experiments were carried out in a water tank to measure the time-averaged velocity and turbulence intensity by using a Laser Doppler Anemometry (LDA) system. The jet was produced by rotating the propeller at a constant speed powered by an electric motor. The maximum tangential and radial velocities of the six-bladed propeller were of 76% and 17% of the maximum axial velocity respectively. The study found that the six-bladed propeller has a lower tangential velocity, but a higher radial velocity with its own diffusing mechanism when comparing to the three-bladed propeller.

Enhancement Factor for Gas Absorption in a Finite Liquid Layer. Part 2: First- and Second-Order Reactions in a Liquid in Plug Flow

Gas absorption accompanied by an irreversible chemical reaction of first-order or second-order in a liquid layer of finite thickness in plug flow has been investigated. The analytical solution to the enhancement factor has been derived for the case of a first-order reaction, and the exact solution to the enhancement factor has been obtained via numerical simulation for the case of a second-order reaction. The enhancement factor in both cases is presented as a function of the Fourier number and tends to deviate from the prediction of the existing enhancement factor expressions based on the penetration theory at Fourier numbers above 0.1 due to the absence of a well-mixed bulk region in the liquid layer. Approximate enhancement factor expressions that describe the analytical and exact solutions with an accuracy of 5?% and 9?%, respectively, have been proposed.

Repeat prescribing of non-steroidal anti-inflammatory drugs excluding aspirin:how careful are we?

About 5% of all National Health Service prescriptions in Britain and a quarter of reports of suspected adverse reactions are accounted for by non-steroidal anti-inflammatory drugs. Their prescription was investigated in two computerised group practices serving 11850 patients. Altogether 198 patients receiving repeat prescriptions of non-steroidal anti-inflammatory drugs were identified and relevant clinical details extracted from their notes. Of these patients, 119 were over 65 years old; 172 were receiving one of six different non-steroidal anti-inflammatory drugs; and 76 were taking drugs that can interact with non-steroidal anti-inflammatory drugs. Ninety one patients had one or more medical conditions that may be aggravated by non-steroidal anti-inflammatory drugs, and 36 had experienced side effects important enough for their treatment to be changed. A questionnaire to assess opinions and knowledge of non-steroidal anti-inflammatory drugs was given to 42 general practitioners and 26 rheumatologists. Although the two groups showed a comparable knowledge of the properties and costs of non-steroidal anti-inflammatory drugs, they differed significantly in their views on the circumstances under which these drugs should be used. Clear guidelines on the prescription of these drugs would indicate when careful monitoring is essential for patients to benefit from them safely.

Development of a five-plex flow cytometric immunoassay for the simultaneous detection of six coccidiostats in feed and eggs

Coccidiostats are the only veterinary drugs still permitted to be used as feed additives to treat poultry for coccidiosis. To protect consumers, maximum levels for their presence in food and feed have been set by the European Union (EU). To monitor these coccidiostats, a rapid and inexpensive screening method would be a useful tool. The development of such a screening method, using a flow cytometry-based immunoassay, is described. The assay uses five sets of colour-coded paramagnetic microspheres for the detection of six selected priority coccidiostats. Different coccidiostats, with and without carrier proteins, were covalently coupled onto different bead sets and tested in combination with polyclonal antisera and with a fluorescent-labelled secondary antibody. The five optimal combinations were selected for this multiplex and a simple-to-use sample extraction method was applied for screening blank and spiked eggs and feed samples. A very good correlation (r ranging from 0.995 to 0.999) was obtained with the responses obtained in two different flow cytometers (Luminex 100 and FLEXMAP 3D). The sensitivities obtained were in accordance with the levels set by the EU as the measured limits of detection for narasin/salinomycin, lasalocid, diclazuril, nicarbazin (4,4'-dinitrocarbanilide) and monensin in eggs were 0.01, 0.1, 0.5, 53 and 0.1 µg/kg and in feed 0.1, 0.2, 0.3, 9 and 1.5 µg/kg, respectively.

Minimizing side reactions in chemoenzymatic dynamic kinetic resolution: organometallic and material strategies

Chemoenzymatic dynamic kinetic resolution (DKR) of rac-1-phenyl ethanol into R-1-phenylethanol acetate was investigated with emphasis on the minimization of side reactions. The organometallic hydrogen transfer (racemization) catalyst was varied, and this was observed to alter the rate and extent of oxidation of the alcohol to form ketone side products. The performance of highly active catalyst [(pentamethylcyclopentadienyl) IrCl2(1-benzyl,3-methyl-imidazol-2-ylidene)] was found to depend on the batch of lipase B used. The interaction between the bio- and chemo-catalysts was reduced by employing physical entrapment of the enzyme in silica using a sol-gel process. The nature of the gelation method was found to be important, with an alkaline method preferred, as an acidic method was found to initiate a further side reaction, the acid catalyzed dehydration of the secondary alcohol. The acidic gel was found to be a heterogeneous solid acid.

Rapid differentiation between fluconazole-sensitive and -resistant species of Candida directly from positive blood-culture bottles by real-time PCR

In view of both the delay in obtaining identification by conventional methods following blood-culture positivity in patients with candidaemia and the close relationship between species and fluconazole (FLC) susceptibility, early speciation of positive blood cultures has the potential to influence therapeutic decisions. The aim was to develop a rapid test to differentiate FLC-resistant from FLC-sensitive Candida species. Three TaqMan-based real-time PCR assays were developed to identify up to six Candida species directly from BacT/Alert blood-culture bottles that showed yeast cells on Gram staining at the time of initial positivity. Target sequences in the rRNA gene complex were amplified, using a consensus two-step PCR protocol, to identify Candida albicans, Candida parapsilosis, Candida tropicalis, Candida dubliniensis, Candida glabrata and Candida krusei; these are the most commonly encountered Candida species in blood cultures. The first four of these (the characteristically FLC-sensitive group) were identified in a single reaction tube using one fluorescent TaqMan probe targeting 1 8S rRNA sequences conserved in the four species. The FLC-resistant species C. krusei and C. glabrata were detected in two further reactions, each with species-specific probes. This method was validated with clinical specimens (blood cultures) positive for yeast (n=33 sets) and the results were 100% concordant with those of phenotypic identification carried out concomitantly. The reported assay significantly reduces the time required to identify the presence of C. glabrata and C. krusei in comparison with a conventional phenotypic method, from ~72 to

Immune reactions to Bacteroides fragilis populations with three different types of capsule in a model of infection

The survival and growth of populations of the obligately anaerobic pathogenic bacterium Bacteroides fragilis enriched for large capsules (LCs), small capsules (SCs) or an electron-dense layer (EDL; non-capsulate by light microscopy) were examined in a mouse model of infection over a minimum period of 20 d. Chambers which allowed the influx of leukocytes, but not the efflux of bacteria, were implanted in the mouse peritoneal cavity. The LC and EDL populations consistently attained viable cell densities of the order of 10(8)-10(9) c.f.u. ml-1 within 24 h, whereas the SC population did not. However, after 3 d, all three bacterial populations maintained total viable numbers of 10(8)-10(9) c.f.u. ml-1 within the chambers. LC expression was selected against within 24 h in the model, the populations becoming non-capsulate by light microscopy, whereas in the SC population expression of the SC was retained by approximately 90% of the population. The EDL population remained non-capsulate by light microscopy throughout. Lymphocytes infiltrated the chambers to an equal extent for all three B. fragilis populations and at approximately 1000 times higher concentration than chambers which contained only quarter-strength Ringer's solution. The presence of neutrophils within the chambers did not cause a decrease in the total viable bacterial count. Each population elicited antibodies specific for outer-membrane proteins and polysaccharide, as detected by immunoblotting, which cross-reacted with the other populations. Differences were observed in the immunogenicity of the outer-membrane proteins within the three populations. Neutrophils were initially the predominant cell type in the chambers, but as the total leukocyte count increased with incubation time, neutrophils were outnumbered by other leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimates of peer effects in adolescent smoking across twenty six European countries

Although it is widely believed that one of the key factors influencing whether an adolescent smokes or not is the smoking behaviour of his or her peers, empirical evidence on the magnitude of such peer effects, and even on their existence, is mixed. This existing evidence comes from a range of studies using a variety of country-specific data sources and a variety of identification strategies. This paper exploits a rich source of individual level, school-based, survey data on adolescent substance use across countries - the 2007 European Schools Survey Project on Alcohol and Other Drugs - to provide estimates of peer effects between classmates in adolescent smoking for 75,000 individuals across 26 European countries, using the same methods in each case. The results suggest statistically significant peer effects in almost all cases. These peer effects estimates are large: on average across countries, the probability that a 'typical' adolescent smokes increases by between.31 and.38 percentage points for a one percentage point increase in the proportion of classmates that smoke. Further, estimated peer effects in adolescent smoking are stronger intra-gender than inter-gender. They also vary across countries: in Belgium, for example, a one percentage point increase in reference group smoking is associated with a.16 to.27 percentage point increase in own smoking probability; in the Netherlands the corresponding increase is between.42 and.59 percentage points. © 2011 Elsevier Ltd.