HPLC-UV determination of metformin in human plasma for application in pharmacokinetics and bioequivalence studies

In this study, a simple, rapid and sensitive HPLC method with UV detection is described for determination of metformin in plasma samples from bioequivalence assays. Sample preparation was accomplished through protein precipitation with acetonitrile and chromatographic separation was performed on a reversed-phase phenyl column at 40 degrees C. Mobile phase consisted of a mixture of phosphate buffer and acetonitrile at flow rate of 1.0 ml/min. Wavelength was set at 236 nm. The method was applied to a bioequivalence study of two drug products containing metformin, and allowed determination of metformin at low concentrations with a higher throughput than previously described methods. (c) 2007 Elsevier B.V. All rights reserved.

Determination of mitragynine in rat plasma by LC-MS/MS: Application to pharmacokinetics

This study used for the first time LC-MS/MS for the analysis of mitragynine (MIT), a mu-opioid agonist with antinociceptive and antitussive properties, in rat plasma. Mitragynine and the internal standard (amitriptyline) were extracted from plasma with hexane-isoamyl alcohol and resolved on a Lichrospher (R) RP-SelectB column (9.80 and 12.90 min, respectively). The quantification limit was 0.2 ng/mL within a linear range of 0.2-1000 ng/mL The method was applied to quantify mitragynine in plasma samples of rats (n = 8 per sampling time) treated with a single oral dose of 20 mg/kg. The following pharmacokinetic parameters were obtained (mean): maximum plasma concentration: 424 ng/mL; time to reach maximum plasma concentration: 1.26 h; elimination half-life: 3.85 h, apparent total clearance: 6.35 L/h/kg, and apparent volume of distribution: 37.90 L/kg. (C) 2009 Elsevier B.V. All rights reserved.

Gypsum solubility in seawater, and its application to bauxite residue amelioration

The solubilities and dissolution rates of three gypsum sources (analytical grade (AG), phosphogypsum (PG) and mined gypsum (MG)) with six MG size fractions ((mm) > 2.0, 1.0-2.0, 0.5-1.0, 0.25-0.5, 0.125-0.25, and < 0.125) were investigated in triple deionised water (TDI) and seawater to examine their suitability for bauxite residue amelioration. Gypsum solubility was greater in seawater (3.8 g L 1) than TDI (2.9 g L 1) due to the ionic strength effect, with dissolution in both TDI and seawater following first order kinetics. Dissolution rate constants varied with gypsum source (AR > PG > MG) due to reactivity and surface area differences, with 1:20 gypsum:solution suspensions reaching saturation within 15 s (AR) to 30 min (MG > 2.0). The ability of bauxite residue to adsorb Ca from solution was also examined. The quantity of the total solution Ca adsorbed was found to be small (5 %). These low rates of solution Ca adsorption combined with the comparatively rapid dissolution rates preclude the application of gypsum to the residue sand/seawater slurry as a method for residue amelioration. Instead, direct field application to the residue would ensure more efficient gypsum use. In addition, the formation of a sparingly soluble CaCO3 coating around the gypsum particles after mixing in a highly alkaline seawater/supernatant liquor (SNL) solution greatly reduced the rate of gypsum dissolution.

Is ultra-rapid opioid detoxification a viable option in the treatment of opioid dependence?

Ultra-rapid opioid detoxification (UROD) involves the acceleration of opioid withdrawal hv administering thp opioid receptor antagonist naltrexone under general anaesthesia. There is evidence from uncontrolled and a few controlled studies that UROD accelerates opioid withdrawal and that it achieves high rates of completion of acute opioid withdrawal. However, there is clear evidence that the use of a general anaesthetic is not required to accelerate withdrawal or to achieve high rates of completion of acute opioid withdrawal. These goals can be achieved by using naltrexone or naloxone to accelerate withdrawal under light sedation, a procedure known as rapid opioid detoxification under sedation (ROD). There is also evidence that use of an opioid antagonist is not required to achieve a high rate of completion of acute opioid withdrawal. The mixed agonist-antagonist buprenorphine has achieved comparable rates of completion in similarly selected patients with fewer withdrawal symptoms. There is no evidence from controlled trials that either UROD or ROD increases the rate of abstinence from opioids 6 or 12 months after withdrawal. UROD and ROD may increase the number of patients who are inducted onto naltrexone maintenance (NM) therapy but extensive experience with NM therapy suggests that it only has a limited role in selected patients. Given the lack of evidence of substantially increased rates of abstinence, and the need for anaesthetists and high dependency beds, UROD has at best a very minor role in the treatment of a handful of opioid dependent patients who are unable to complete withdraw in any other way. ROD may have more of a role as one option for opioid withdrawal in well motivated patients who want to be rapidly inducted onto NM therapy or who want to enter other types of abstinence-oriented treatment.

Encoding combinatorial libraries: A novel application of fluorescent silica colloids

A major challenge associated with using large chemical libraries synthesized on microscopic solid support beads is the rapid discrimination of individual compounds in these libraries. This challenge can be overcome by encoding the beads with 1 mum silica colloidal particles (reporters) that contain specific and identifiable combinations of fluorescent byes. The colored bar code generated on support beads during combinatorial library synthesis can be easily, rapidly, and inexpensively decoded through the use of fluorescence microscopy. All reporters are precoated with polyelectrolytes [poly(acrylic acid), PAA, poly(sodium 4-styrenesulfonate PSSS, polyethylenimine, PEI, and/or poly(diallyldimethylammonium chloride), PDADMAC] with the aim of enhancing surface charge, promoting electrostatic attraction to the bead, and facilitating polymer bridging between the bead and reporter for permanent adhesion. As shown in this article, reporters coated with polyelectrolytes clearly outperform uncoated reporters with regard to quantity of attached reporters per bead (54 +/- 23 in 2500 mum(2) area for PEI/PAA coated and 11 +/- 6 for uncoated reporters) and minimization of cross-contamination (1 red reporter in 2500 mum(2) area of green-labeled bead for PEI/PAA coated and 26 +/- 15 red reporters on green-labeled beads for uncoated reporters after 10 days). Examination of various polyelectrolyte systems shows that the magnitude of the xi -potential of polyelectrolyte-coated reporters (-64 mV for PDADMAC/PSSS and -42 mV for PEI/PAA-coated reporters) has no correlation with the number of reporters that adhere to the solid support beads (21 +/- 16 in 2500 mum(2) area for PDADMAC/PSSS and 54 +/- 23 for PEI/PAA-coated reporters). The contribution of polymer bridging to the adhesion has a far greater influence than electrostatic attraction and is demonstrated by modification of the polyelectrolyte multilayers using gamma irradiation of precoated reporters either in aqueous solution or in polyelectrolyte solution.

Rapid increases in cytokinin concentration in lateral buds of chickpea (Cicer arietinum L) during release of apical dominance

We examined the role of cytokinins (CKs) in release of apical dominance in lateral buds of chickpea (Cicer arietinum L.). Shoot decapitation or application of CKs (benzyladenine, zeatin or dihydrozeatin) stimulated rapid bud growth. Time-lapse video recording revealed growth initiation within 2 h of application of 200 pmol benzyladenine or within 3 h of decapitation. Endogenous CK content in buds changed little in the first 2 h after shoot decapitation, but significantly increased by 6 h, somewhat later than the initiation of bud growth. The main elevated CK was zeatin riboside, whose content per bud increased 7-fold by 6 h and 25-fold by 24 h. Lesser changes were found in amounts of zeatin and isopentenyl adenine CKs. We have yet to distinguish whether these CKs are imported from the roots via the xylem stream or are synthesised in situ in the buds, but CKs may be part of an endogenous signal involved in lateral bud growth stimulation following shoot decapitation. To our knowledge, this is the first detailed report of CK levels in buds themselves during release of apical dominance.

Inhibition of spontaneous neurotransmission in the nucleus of solitary tract of the rat by the cannabinoid agonist WIN 55212-2 is not via CB1 or CB2 receptors

Cannabinoids have been shown to modulate central autonomic regulation and baroreflex control of blood pressure. Both CB1 and CB2 cannabinoid receptors have been described in the nucleus tractus solitarius (NTS), which receives direct afferent projections of cardiovascular reflexes. in the present study we evaluated the effects of WIN 55212-2 (WIN), a cannabinoid agonist, on fast neurotransmission in the NTS. We recorded spontaneous post-synaptic currents using the whole-cell configuration in NTS cells in brainstem slices from young rats (25-30 days old). Application of 5 mu M WIN inhibited the frequency of both glutamatergic and GABAergic sPSCs, without affecting their amplitudes. Effects of WIN were not blocked by application of the CB1 antagonist AM251, the CB2 antagonist AM630 or the varmiloid receptor TRPV1 antagonist AMG9810, suggesting that the effect of WIN is via a non-CB1 non-CB2 receptor. Neither the CB1/CB2 agonist HU210 nor the CB1 agonist ACPA affected the frequency of sPSCs. We conclude WIN inhibits the neurotransmission in the NTS of young rats via a receptor distinct from CB1 or CB2. (c) 2008 Elsevier B.V. All rights reserved.

Identifying trajectories of adolescent smoking: An application of latent growth mixture modeling

The goal of the current study was to identify discrete longitudinal patterns of change in adolescent smoking using latent growth mixture modeling. Five distinct longitudinal patterns were identified. A group of early rapid escalators was characterized by early escalation (at age 13) that rapidly increased to heavy smoking. A pattern characterized by occasional puffing up until age 15, at which time smoking escalated to moderate levels was also identified (late moderate escalators). Another group included adolescents who, after age 15, began to escalate slowly in their smoking to light (0.5 cigarettes per month) levels (late slow escalators). Finally, a group of stable light smokers (those who smoked 1-2 cigarettes per month) and a group of stable puffers (those. who smoked only a few puffs per month) were also identified. The stable puffer group was the largest group and represented 25% of smokers.

A rapid method for determining recent sunscreen use in field studies

The role of sunscreens in preventing skin cancer and melanoma is the focus of ongoing research. Currently, there is no objective measure which can be used in field studies to determine whether a person has applied sunscreen to their skin, and researchers must use indirect assessments such as questionnaires. We sought to develop a rapid, non-invasive method for identifying sunscreen on the skin for use in epidemiological studies. Our basic method is to swab the skin, elute any residues which have been adsorbed onto the swab by rinsing in ethanol, and submit the eluted washings for spectrophotometric analysis. In a controlled study, we applied 0.1 ml of sunscreen to a 50 cm(2) grid on both forearms of 21 volunteers. Each forearm was allocated one of 10 different sunscreen brands. The skin was swabbed after intervals of 20 min, 1 h, 2 h and 4 h. In a field study conducted among 12 children aged 2-4 years attending a child care centre, sunscreen was applied to the faces of half the children. Swabs were then taken from the face and back of all children without knowledge of sunscreen status. In the controlled study, sunscreen was clearly detectable up to 2 h after application for all brands containing organic sunscreen, and marginally detectable at 4 h. In the field study, this method correctly identified all children with and without sunscreen. We conclude that spectrophotometric analysis of skin swabs can reliably detect the presence of sunscreen on the skin for up to 2 It after application. (C) 2002 Elsevier Science B.V. All rights reserved.

A creative solution for rapid and inexpensive model-making in product design processes

Innovative Developments in Virtual and Physical Prototyping

A creative solution for rapid and inexpensive model-making in product design processes

Rapid prototyping (RP) is an approach for automatically building a physical object through solid freeform fabrication. Nowadays, RP has become a vital aspect of most product development processes, due to the significant competitive advantages it offers compared to traditional manual model making. Even in academic environments, it is important to be able to quickly create accurate physical representations of concept solutions. Some of these can be used for simple visual validation, while others can be employed for ergonomic assessment by potential users or even for physical testing. However, the cost of traditional RP methods prevents their use in most academic environments on a regular basis, and even for very preliminary prototypes in many small companies. That results in delaying the first physical prototypes to later stages, or creating very rough mock-ups which are not as useful as they could be. In this paper we propose an approach for rapid and inexpensive model-making, which was developed in an academic context, and which can be employed for a variety of objects.

Interpretation of the presence of IgM and IgG antibodies in a rapid test for dengue: analysis of dengue antibody prevalence in Fortaleza City in the 20th year of the epidemic

INTRODUCTION: The diagnosis of dengue and the differentiation between primary and secondary infections are important for monitoring the spread of the epidemic and identifying the risk of severe forms of the disease. The detection of immunoglobulin (Ig)M and IgG antibodies is the main technique for the laboratory diagnosis of dengue. The present study assessed the application of a rapid test for dengue concerning detection of new cases, reinfection recognition, and estimation of the epidemic attack rate. METHODS: This was a retrospective, cross-sectional, descriptive study on dengue using the Fortaleza Health Municipal Department database. The results from 1,530 tested samples, from 2005-2006, were compared with data from epidemiological studies of dengue outbreaks in 1996, 2003, and 2010. RESULTS: The rapid test confirmed 52% recent infections in the tested patients with clinical suspicion of dengue: 40% detected using IgM and 12% of new cases using IgG in the non-reactive IgM results. The positive IgM plus negative IgG (IgM+ plus IgG-) results showed that 38% of those patients had a recent primary dengue infection, while the positive IgG plus either positive or negative IgM (IgG+ plus IgM+/-) results indicated that 62% had dengue for at least a second time (recent secondary infections). This proportion of reinfections permitted us to estimate the attack rate as >62% of the population sample. CONCLUSIONS: The rapid test for dengue has enhanced our ability to detect new infections and to characterize them into primary and secondary infections, permitting the estimation of the minimal attack rate for a population during an outbreak.

ParallelKnoppix - Rapid deployment of a linux cluster for MPI parallel processing using non-dedicated computers

This note describes ParallelKnoppix, a bootable CD that allows creation of a Linux cluster in very little time. An experienced user can create a cluster ready to execute MPI programs in less than 10 minutes. The computers used may be heterogeneous machines, of the IA-32 architecture. When the cluster is shut down, all machines except one are in their original state, and the last can be returned to its original state by deleting a directory. The system thus provides a means of using non-dedicated computers to create a cluster. An example session is documented.

Validation of an analytical method for nitrous oxide (N2O) laughing gas by headspace gas chromatography coupled to mass spectrometry (HS-GC-MS): Forensic application to a lethal intoxication.

Drug abuse is a widespread problem affecting both teenagers and adults. Nitrous oxide is becoming increasingly popular as an inhalation drug, causing harmful neurological and hematological effects. Some gas chromatography-mass spectrometry (GC-MS) methods for nitrous oxide measurement have been previously described. The main drawbacks of these methods include a lack of sensitivity for forensic applications; including an inability to quantitatively determine the concentration of gas present. The following study provides a validated method using HS-GC-MS which incorporates hydrogen sulfide as a suitable internal standard allowing the quantification of nitrous oxide. Upon analysis, sample and internal standard have similar retention times and are eluted quickly from the molecular sieve 5Å PLOT capillary column and the Porabond Q column therefore providing rapid data collection whilst preserving well defined peaks. After validation, the method has been applied to a real case of N2O intoxication indicating concentrations in a mono-intoxication.

Hydrogeophysical data integration at larger scales: Application of Bayesian sequential simulation for the characterization of heterogeneous alluvial aquifers

Knowledge of the spatial distribution of hydraulic conductivity (K) within an aquifer is critical for reliable predictions of solute transport and the development of effective groundwater management and/or remediation strategies. While core analyses and hydraulic logging can provide highly detailed information, such information is inherently localized around boreholes that tend to be sparsely distributed throughout the aquifer volume. Conversely, larger-scale hydraulic experiments like pumping and tracer tests provide relatively low-resolution estimates of K in the investigated subsurface region. As a result, traditional hydrogeological measurement techniques contain a gap in terms of spatial resolution and coverage, and they are often alone inadequate for characterizing heterogeneous aquifers. Geophysical methods have the potential to bridge this gap. The recent increased interest in the application of geophysical methods to hydrogeological problems is clearly evidenced by the formation and rapid growth of the domain of hydrogeophysics over the past decade (e.g., Rubin and Hubbard, 2005).