Micro-Structural Analysis of Tablet Surface Layers by Intelligent Laser Speckle Classification (<Emphasis Type="Italic">ILSC</Emphasis>) Technique: an Application in the Study of both Surface Defects and Subsurface Granule Structures

Purpose

As a consequence of the latest developments in laser technologies it is now possible to develop a low-cost and accurate tablet inspection system by the unification of optical and artificial intelligence methods.

Method

The functionality of the proposed system is based on a sequence of texture analysis of laser speckle images (using laser sources of 650 and 808 nm, VIS/IR) followed by the optimization of texture parameters using Bayesian Networks (BN).

Results

In the first part of this work, a Bayesian inference method was used to detect microscale tablet defects that are generated “progressively” during production whereas in the second part a Bayesian classifier method was used to discriminate between tablets made from different granule sizes. In part two, it was shown that (i) the comparatively higher energy (5 mW) IR laser light generates different speckle effects than the lower energy visible (Red 3 mW) by interacting with deeper subsurface of the tablets and (ii) by using multi-classifier systems (MCS) to fuse the Bayesian classifiers from both types of speckle images it was possible to achieve a higher discrimination power (88% classification accuracy) for distinguishing between tablets made from different granule sizes than one can achieve from a single image type.

Conclusion

It is suggested that this unified method has the potential to provide for a comprehensive analysis of both tablet quality attributes, on the one hand, and failure modes, on the other, that might be used in the development of a low-cost tablet inspection system.

     

The epidemiological impact of antiretroviral use predicted by mathematical models: a review

This review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented.     

First report and toxicological assessment of the cyanobacterium Cylindrospermopsis raciborskii from Portuguese freshwaters

The freshwater cyanobacterium Cylindrospermopsis raciborskii has become increasingly prevalent in freshwaters worldwide. This species is a concern from a water quality perspective due to its known ability to produce a potent hepatotoxic alkaloid cylindrospermopsin, which has been implicated in outbreaks of human sickness and cattle mortality. C. raciborskii strains isolated from Brazil have also been found to produce the highly toxic paralytic shellfish poisons (PSPs). This article reports the toxicity of four strains of C. raciborskii taken from three reservoirs and one river in Portugal, as well as the occurrence of this species in other water bodies used for potable and recreational purposes. All four strains grown in pure culture in the laboratory were found to be toxic in the mouse bioassay at 8-24h after intraperitoneal administration of single doses ranging from 1337 to 1572 mgkg(-1) Histological examination indicated that liver damage was the primary lesion; in addition, there was inflammation in the intestine. HPLC/MS tests for the presence of cylindrospermopsin, microcystins, and PSP toxins were negative. The available evidence suggests that another toxin may be present. This constitutes the first report of toxic C. raciborskii in Europe and draws attention to the need for increased monitoring of this cyanobacterium in water bodies used for potable and recreational purposes.     

Application of the neuroblastoma assay for paralytic shellfish poisons to neurotoxic freshwater cyanobacteria: interlaboratory calibration and comparison with other methods of analysis

Paralytic shellfish poisons (PSPs) are produced by freshwater cyanobacteria and pose a threat to human and animal drinking-water supplies. The wide range of toxin analogues (and the likelihood that further analogues remain to be discovered) means that chromatographic methods are not always reliable indicators of toxicity. Although the mouse bioassay remains the method of choice in the seafood industry, its use is increasingly being questioned on ethical grounds. The cell-based Neuro-2A neuroblastoma toxicity assay is an alternative bioassay validated for testing shellfish extracts, so it was of interest to determine its applicability with the different suite of toxin analogues produced by cyanobacteria. Cyanobacterial bloom samples from Australia, Brazil, and France were assayed using the neuroblastoma assay, liquid chromatography-tandem mass spectrometry (LC-MS/MS), high-performance liquid chromatography with postcolumn derivatization and fluorescence detection, and the Jellett Rapid Test for PSP. To assess interlaboratory variability, the neuroblastoma assay was set up in laboratories in Paris (France) and Adelaide (Australia). Neuroblastoma and chromatographic methods gave comparable results except in the case of the neurotoxic Brazilian samples: LC-MS/MS did not detect the putative new PSPs contained in these samples. Inter- and intralaboratory variability of the neuroblastoma assay was typical of biological assays but no greater than that found for interassay variability between different chromatographic determinations. The batch of Jellett Rapid Tests for PSP used did not yield quantitative results. Overall, the neuroblastoma assay was useful as a screening assay for determination of toxicity caused by saxitoxin neurotoxins in freshwater cyanobacteria, having the advantage of being sensitive to unidentified toxins that currently cannot be quantified by chromatographic means.     

Antioxidant activities of extracts from five anti-viral medicinal plants

The antioxidant activities of five medicinal plants (Ampelopsis sinica, Ampelopsis humiliforlia var. heterophylla, Potentilla freyniana, Selaginella labordei and Chrysanthemum multiflorum), used in the Hubei province of China, have been investigated using both enzymatic and non-enzymatic in vitro antioxidant assays. Extracts from all five of the plants inhibited xanthine oxidase and lipoxygenase activities, and were scavengers of the ABTS*+ radical cation using the Trolox equivalent antioxidant capacity assay (TEAC). Extracts from Potentilla freyniana and Selaginella labordei down-regulated cyclooxygenase-2 gene expression, measured by real-time RT-PCR, in human colon adenocarcinoma CaCo-2 cells.     

Pharmacokinetic profile of Mitoguazone (MGBG) in patients with AIDS related non-Hodgkin's lymphoma

Summary Mitoguazone is a unique chemotherapeutic agent whose activity is believed to result primarily from the competitive inhibition of S-adenosyl-methionine decarboxylase leading to a disruption in polyamine biosynthesis. Initial clinical trials demonstrated that the dose-limiting toxicities (mucositis and myelosuppression) of Mitoguazone were both dose and schedule dependent. Early pharmacokinetic studies of Mitoguazone in man revealed a prolonged half-life. Concurrent with a recent Phase II trial of Mitoguazone in patients with AIDS related non-Hodgkin's lymphoma, the single dose pharmacokinetics of Mitoguazone were characterized. Twelve patients received 600 mg/m² of intravenous Mitoguazone over 30 minutes on an intermittent every 2 week schedule. Blood, urine, cerebrospinal fluid (CSF), pleural fluid and tissue samples were collected and analyzed by HPLC. Mitoguazone was cleared from the plasma triexponentially with a harmonic mean terminal half-life of 175 hours and a mean residence time of 192 hours. Peak plasma levels occurred immediately post-infusion, ranged from 6.47 to 42.8 g/ml, and remained (for an extended period) well above the reported concentration for inhibition of polyamine biosynthesis. Plasma clearance averaged 4.73 l/hr/m² with a relatively large apparent volume of distribution at steady-state of 1012 l/m² indicating tissue sequestration. Renal excretion of unchanged Mitoguazone accounted for an average of 15.8% of the dose within 48 to 72 hours post-administration. Detectable levels of drug were present in random voided samples eight days post-dose. Mitoguazone levels in CSF ranged from 22 to 186 ng/ml post-dose with CSF/plasma ratios ranging from 0.6% to 7%. The pleural fluid/plasma ratio was approximately 1. Tissue levels of Mitoguazone were highest in the liver followed by lymph node, spleen and the brain.     

Fear of crime and health in residential tower blocks. A case study in Liverpool, UK

BACKGROUND: Though it is often assumed that fear of crime erodes mental health, research evidence is limited. Our study seeks to assess the relationship between these attributes in residents of the city of Liverpool. METHOD: Evidence is drawn from a sample survey of 407 adults living in 21 tower blocks. A number of social and psychosocial attributes linked with feelings of safety are compared with self-reported health status using logistic and multiple regression techniques. Possible reciprocal relationships were investigated using two-stage least squares. RESULTS: Fear of crime in this sample is generally much lower in the home than in Britain as a whole and much higher out on the neighbouring streets at night, but there are sub-group variations. We find significant associations between fear of crime and health status. Feelings of safety when out alone after dark is the most consistent predictor of health status. Those feeling safe score significantly higher on all five dimensions of the SF-36 measure which cover mental and social well-being. Mental health is the strongest correlate and is probably a consequence rather than cause of feelings of safety. CONCLUSION: The evidence suggests elderly residents believe tower blocks provide safe accommodation. However, feelings of safety in these 'fortresses' do not generally extend to walking in neighbouring streets. Fear of crime erodes quality of life and is associated with poorer health.     

Solubilities of Crystalline Drugs in Polymers: An Improved Analytical Method and Comparison of Solubilities of Indomethacin and Nifedipine in PVP,PVP/VA,and PVAc

A previous method for measuring solubilities of crystalline drugs in polymers has been improved to enable longer equilibration and used to survey the solubilities of indomethacin (IMC) and nifedipine (NIF) in two homo-polymers [polyvinyl pyrrolidone (PVP) and polyvinyl acetate (PVAc)] and their co-polymer (PVP/VA). These data are important for understanding the stability of amorphous drug-polymer dispersions, a strategy actively explored for delivering poorly soluble drugs. Measuring solubilities in polymers is difficult because their high viscosities impede the attainment of solubility equilibrium. In this method, a drug-polymer mixture prepared by cryomilling is annealed at different temperatures and analyzed by differential scanning calorimetry to determine whether undissolved crystals remain and thus the upper and lower bounds of the equilibrium solution temperature. The new annealing method yielded results consistent with those obtained with the previous scanning method at relatively high temperatures, but revised slightly the previous results at lower temperatures. It also lowered the temperature of measurement closer to the glass transition temperature. For d-mannitol and IMC dissolving in PVP, the polymer’s molecular weight has little effect on the weight-based solubility. For IMC and NIF, the dissolving powers of the polymers follow the order PVP > PVP/VA > PVAc. In each polymer studied, NIF is less soluble than IMC. The activities of IMC and NIF dissolved in various polymers are reasonably well fitted to the Flory-Huggins model, yielding the relevant drug-polymer interaction parameters. The new annealing method yields more accurate data than the previous scanning method when solubility equilibrium is slow to achieve. In practice, these two methods can be combined for efficiency. The measured solubilities are not readily anticipated, which underscores the importance of accurate experimental data for developing predictive models. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4023–4031, 2010