The influence of rotational error and axial shift of toric intraocular lenses on residual astigmatism.

Purpose: Accurate alignment of Toric Intraocular Lens (T-IOLs) in cataract surgery is crucial for good visual outcomes. The purpose of this study was to evaluate the influence of rotation, axial shift and their combined effects on the refractive error and image quality of a wide range of T-IOL powers (from +1.50 D to +6.

Multi-toric optical element to compensate ocular astigmatism with increased tolerance under rotation.

A new, to the best of our knowledge, optical element designed to compensate regular astigmatism while exhibiting increased tolerance to rotational misalignment is introduced. The element incorporates an optical design based on concentric annular regions with slightly different cylindrical axis angular positions. To assess visual quality performance as a function of rotation, retinal image simulation and clinical assessments with an adaptive optics visual simulator were carried out.

Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. Identification of a suitable "back-up" compound for N-tert-butyl isoquine.

On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline amodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed ADME studies and in vitro and in vivo toxicological assessment. 4'-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as a candidate for further development studies based on potent activity versus chloroquine-sensitive and resistant parasites, moderate to excellent oral bioavailability, low toxicity in in vitro studies, and an acceptable safety profile.

Candidate selection and preclinical evaluation of N-tert-butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for the 21st century.

N-tert-Butyl isoquine (4) (GSK369796) is a 4-aminoquinoline drug candidate selected and developed as part of a public-private partnership between academics at Liverpool, MMV, and GSK pharmaceuticals. This molecule was rationally designed based on chemical, toxicological, pharmacokinetic, and pharmacodynamic considerations and was selected based on excellent activity against Plasmodium falciparum in vitro and rodent malaria parasites in vivo. The optimized chemistry delivered this novel synthetic quinoline in a two-step procedure from cheap and readily available starting materials.

Effect of the haematocrit layer geometry on Plasmodium falciparum static thin-layer in vitro cultures.

Background: In vitro cultivation of Plasmodium falciparum is usually carried out through the continuous preservation of infected erythrocytes deposited in static thin layers of settled haematocrit. This technique, called the candle-jar method, was first achieved by Trager and Jensen in 1976 and has undergone slight modifications since then. However, no systematic studies concerning the geometry of the haematocrit layer have been carried out.

Two-step synthesis of achiral dispiro-1,2,4,5-tetraoxanes with outstanding antimalarial activity, low toxicity, and high-stability profiles.

A rapid, two-step synthesis of a range of dispiro-1,2,4,5-tetraoxanes with potent antimalarial activity both in vitro and in vivo has been achieved. These 1,2,4,5-tetraoxanes have been proven to be superior to 1,2,4-trioxolanes in terms of stability and to be superior to trioxane analogues in terms of both stability and activity. Selected analogues have in vitro nanomolar antimalarial activity and good oral activity and are nontoxic in screens for both cytotoxicity and genotoxicity.

Individual-based model and simulation of Plasmodium falciparum infected erythrocyte in vitro cultures.

Malaria is still one of the most fatal diseases in the world. Development of an effective treatment or vaccine requires the cultivation of the parasite that causes it: Plasmodium falciparum. Several methods for in vitro cultivation of P.

Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel anti-malarial mitochondrial electron transport inhibitor.

GW844520 is a potent and selective inhibitor of the cytochrome bc1 complex of mitochondrial electron transport in P. falciparum, the parasite primarily responsible for the mortality associated with malaria worldwide. GW844520 is fully active against the parasite including resistance isolates, showing no cross resistance with agents in use.

Computer-assisted enhanced volumetric segmentation magnetic resonance imaging data using a mixture of artificial neural networks.

An accurate computer-assisted method able to perform regional segmentation on 3D single modality images and measure its volume is designed using a mixture of unsupervised and supervised artificial neural networks. Firstly, an unsupervised artificial neural network is used to estimate representative textures that appear in the images. The region of interest of the resultant images is selected by means of a multi-layer perceptron after a training using a single sample slice, which contains a central portion of the 3D region of interest.

Candida albicans infection enhances immunosuppression induced by cyclophosphamide by selective priming of suppressive myeloid progenitors for NO production.

Systemic infections caused by fungi after cytoreductive therapies are especially difficult to deal with in spite of currently available antimicrobials. However, little is known about the effects of fungi on the immune system of immunosuppressed hosts. We have addressed this by studying the in vitro T cell responses after systemic infection with Candida albicans in cyclophosphamide-treated mice.

Monitoring acute inflammatory processes in mouse muscle by MR imaging and spectroscopy: a comparison with pathological results.

We have studied an animal model of acute local inflammation in muscle induced by Aspergillus fumigatus by using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We have compared our data to those found using histopathology and segmentation maps obtained by the mathematical processing of three-dimensional T2-weighted MRI data via a neural network. The MRI patterns agreed satisfactorily with the clinical and biological evidence of the phases of acute local infection and its evolution towards chronicity.

Nitric oxide-producing CD11b(+)Ly-6G(Gr-1)(+)CD31(ER-MP12)(+) cells in the spleen of cyclophosphamide-treated mice: implications for T-cell responses in immunosuppressed mice.

During recovery from intensive chemotherapy with cyclophosphamide (CTX), mice suffer a severe but transitory impairment in spleen cell proliferation to T-cell mitogens (Con A or anti-CD3 plus IL-2). Although CTX treatment reduced spleen T-cell cellularity, this cannot fully account for T-cell unresponsiveness. The results showed that CTX induces the colonization of spleen by an immature myeloid CD11b(+)Ly-6G(+)CD31(+) population.

Bacteriocin 28b, a chromosomally encoded bacteriocin produced by most Serratia marcescens biotypes.

Twenty-six Serratia marcescens strains belonging to fifteen different biotypes were found to produce bacteriocins active against Escherichia coli. On the basis of the pattern of bacteriocin sensitivity of E. coli mutant strains, immunological assays and Southern blot hybridization with a probe for the S.

Cloning and DNA sequence analysis of a bacteriocin gene of Serratia marcescens.

Serratia marcescens N28b synthesized and secreted a bacteriocin, with a molecular mass of 45 kDa, which was capable of inhibiting the growth of Escherichia coli. The expression of this bacteriocin was negligible unless induced with mitomycin C. The genes encoding the bacteriocin were cloned in plasmid pBR328.

Activity of E-3846, a new fluoroquinolone, in vitro and in experimental cystitis and pyelonephritis in rats.

The in vitro antibacterial activity of E-3846, a new fluoroquinolone carboxylic acid derivative with a pyrrol ring substituent at position 7, was evaluated in comparison with norfloxacin and ciprofloxacin. E-3846 was more active than the reference quinolones against Staphylococcus species, including methicillin-resistant strains. E-3846 was similar to ciprofloxacin and more active than norfloxacin against Streptococcus (Enterococcus) faecalis.

Glucose-6-phosphate dehydrogenase alloenzymes and their relationship to pigmentation in Serratia marcescens.

A comparative study of environmental and clinical isolates of Serratia marcescens was undertaken with regard to glucose-6-phosphate dehydrogenase (G6PD) electrophoretic mobility and the production of prodigiosin. Two electromorphs of G6PD with electrophoretic mobilities of 0.22 and 0.

Morphological characterization of the Serratia marcescens bacteriophage SLP.

SLP is a lambda-like bacteriophage specific for Serratia marcescens strains. Morphological studies have demonstrated that SLP virions present two cross-bar structures on its tail not described in bacteriophages specific for Enterobacteriaceae. SDS-polyacrylamide gel electrophoresis of major capsid proteins as well as electron micrographs are reported.