Dilute-solution properties are important sources of information on the structure of macromolecules. Analyzing experimental data and extracting information on structural properties require theoretical and computational resources. The resources needed to study rigid particles are manageable; however, studying flexible particles is more challenging. This is because, unlike rigid bodies, and as a consequence of the conformational variability arising from flexibility, flexible particles do not have a definite size and shape. In addition to their overall translational and rotational Brownian motion, the dynamics of flexible particles in solution has an internal component: size/shape conformational fluctuations. In order to facilitate the study of flexible macromolecule hydrodynamics, we have implemented existing theories within several computer programs. MONTEHYDRO combines Monte Carlo simulations based on the importance-sampling algorithm to generate conformations from which, in addition to conformational quantities, the hydrodynamic properties of flexible particles can be obtained using rigid-body treatment. SIMUFLEX is a suite based on a Brownian dynamics simulation of macromolecules, comprising BROWFLEX, for the generation of trajectories, and ANAFLEX, for the calculation of static and time-dependent properties as well as the simulation of single-particle events. In this paper, we present some concepts which are fundamental to the methods implemented in those computational tools, as well as examples of their utilization in various biomacromolecule applications, with a particular emphasis on double-stranded DNA in various cases: coarse-grained double-helical models for moderately short DNA; the worm-like model treatment of DNA over an extremely wide range of sizes (from 8 to 200,000 base pairs); and the problem of the anomalous rotational-speed dependence of the sedimentation coefficient of very long DNA. SIMUFLEX has also been particularly useful for studying intrinsically partially disordered proteins, whose structure comprises both ordered, globular domains as well as flexible tail and linker chains. To illustrate applications in the field of synthetic polymers, we describe a study on dendrimers, with aspects related to drug delivery in targeted therapies.

A computer programs suite, SIMUFLEX, has been constructed for the calculation of solution properties of flexible macromolecules modeled as bead-and-connector models of arbitrary topology. The suite consists mainly of two independent programs, BROWFLEX that generates the macromolecular trajectory by using the Brownian dynamics technique and ANAFLEX that analyzes that trajectory to get solution properties of the macromolecule. In this paper, we describe theoretical aspects about the macromolecular model and the Brownian dynamics algorithm used and describe some of the numerous properties that can be evaluated. In order to provide examples of the application of the methodology, we present simulations of dynamic properties of DNA with length ranging from 10 to 10(5) base pairs. SIMUFLEX is able to run simulations with more or less coarse-grained models, thus enabling such multiple-scale studies.

This study aimed at evaluating the incorporation of two antimicrobial drugs (nystatin and polynoxylin) as regards: the effect of the liner on the activity of the drug, determination of the least effective concentration of each drug and its duration of action, as well as assessment of the effect of the drug on the mechanical properties and the chemical composition of the liner. Results showed that nystatin added to denture liners in three different concentrations by weight (3%, 5%, 10%) acted effectively against Candida albicans, and that there was a direct relationship between concentration of Nystatin and its duration of action. The inhibitory effect of nystatin (10%) lasted for at least 32 weeks (end of study period). Furthermore, this concentration did not affect the strength properties of the liner. On the other hand, polynoxylin inhibited a number of strains of bacteria and Candida only in high concentrations (40-60%), and these concentrations adversely affected the strength properties of the liner.

An assessment of two dressings used in the treatment of the toenail bed, comparing healing rates and complications reported.

To prevent ascending urinary infection in patients following transurethral prostatectomy, we have studied the use of a topical antibacterial agent applied to the groin and external genitalia. A prospective randomized controlled trial was conducted, with 50 patients being treated by daily application of a 2% polynoxylin powder, and 50 patients acting as untreated controls. Patient age and duration of catheterization were similar in the treated and untreated groups. No significant benefit was seen in the treated cohort (P greater than 0.05) in terms of reduction in postoperative urinary infection.

The antimicrobial activity of polynoxylin, an alkali urea-formaldehyde condensation product, has been examined. The minimum inhibitory concentration (MIC) for 1000 clinical isolates of bacteria and yeasts was in the range 1024-16,384 mg/l. Cidal concentrations of the drug were within one dilution of the corresponding values for MIC, the results suggest a cumulative mode of antimicrobial activity. Formaldehyde, the putative active component of polynoxylin, was released into water from 10% (w/w) cream preparation which gave a maximum yield of 1.56 mg within 6 h. The limited water solubility of polynoxylin, cumulative mode of antimicrobial action and presence of pre-formed formaldehyde in the pharmaceutical preparation, suggest the possibility of sustained activity when applied to skin. The slow solubilization of particulate polynoxylin and gradual liberation of inhibitory degradation products may further enhance the inherent antimicrobial activity afforded by the presence of pre-formed formaldehyde.

Polynoxylin and noxythiolin (Anaflex and Noxyflex) have been recommended for the treatment of certain bacterial infections. Both compounds were shown to release formaldehyde. Detailed studies with noxythiolin showed that it decomposed in solution to liberate most of its formaldehyde, and that solutions of formaldehyde of the appropriate strength gave zones of inhibition on seeded plates comparable in size with those given by noxythiolin. It is suggested that the effects observed with these compounds are caused by the formaldehyde released.