Biomedical subjects

Mark Wainwright

Publications and source records attributed to Mark Wainwright.

9 recordsLinked to original sources

PubMed2006

Phenothiazinium derivatives for pathogen inactivation in blood products.

Phenothiazine-based photosensitisers have been employed in photoantimicrobial research for nearly 80 years, both as lead and novel compounds. However, the main structural variations have mainly involved the auxochromic side chains and little has been reported concerning either peripheral substitution or structures with chromophores other than those of the phenothiazinium or annelated benzo[a]phenothiazinium type. In terms of application, the phenothiazinium series has featured commonly in cytology and cytopathology, as well as in haematological staining. The current work covers the evolution of improved photosensitisers based on the phenothiazine ring system, with particular reference to the field of pathogen inactivation, and the structural alteration of lead compounds such as methylene blue and Nile blue to yield improved photosensitisers for this important aspect of blood product safety.

Blood↗

PubMed2006

Phenothiazinium-based photobactericidal materials.

Photosensitisers based on the phenothiazinium chromophore have been reported to be bactericidal on illumination via a singlet oxygen-mediated mechanism. The current work reports on the immobilisation of the methylene blue analogue, new methylene blue, in polymer resins, and the preliminary development of photobactericidal materials. The resultant materials exhibited measurable levels of singlet oxygen and were photobactericidal against both Staphylococcus epidermidis and Escherichia coli. Such materials may be of use in surface disinfection/infection control in the healthcare milieu.

Anti-Bacterial Agents↗

PubMed2005

The phenothiazinium chromophore and the evolution of antimalarial drugs.

The phenothiazinium salt methylene blue [3,7-bis(dimethylamino)phenothiazinium chloride] is the oldest known synthetic antimalarial drug, its clinical efficacy having been reported in 1891. The role of methylene blue in the evolution of the modern antimalarial armoury is often unappreciated, yet it can be linked directly to standard drugs such as chloroquine and its congeners. Also, in the face of increasing plasmodial resistance to modern antimalarials, phenothiazinium derivatives have again featured as lead compounds in drug research. The precise mode of action of methylene blue and its commercial analogues against Plasmodium spp. remains a cause for conjecture, having been variously described as nucleic acid intercalation, food vacuole basification, parasite redox cycle interference and haem polymerization inhibition. That the activity of the series may be due to more than one route - i.e. a multifactorial activity - underlines the utility of these compounds in antimalarial research either as single drugs or as adjuvants (partners in a drug combination), particularly in the face of resistant parasitic strains.

Animals↗

PubMed2004

Photoinactivation of viruses.

Although the photodynamic effect was demonstrated against viral targets more than seventy years ago, the use of photosensitisers as antivirals in vivo has been slow in gaining acceptance. From a clinical viewpoint, this may be due to the pronounced side effects produced in several cases of the phototreatment of herpes genitalis in the early 1970s, the unfortunate patients presenting with post-treatment Bowen's disease. Currently, the clinical use of photosensitisers in this field is limited to the treatment of laryngeal papillomata. However, considerable progress has been made in the photodynamic disinfection of blood products. Photoantivirals have traditionally been targeted at viral nucleic acid, in many cases via an intercalative mechanism. However, given the potential for deleterious sequelae associated with this route, the design of new photosensitisers should encourage alternative targets, such as viral enzymes or the cell envelope (where this exists). Targeting is obviously determined by the chemistry of the photosensitiser employed and there are many different structural types available. The chemistry, photochemistry and cellular effects of the various agents are discussed, along with future prospects for this exciting area of medicine.

Antiviral Agents↗

PubMed2004

Genetic and environmental sources of covariance between reading tests used in neuropsychological assessment and IQ subtests.

In this study, we examined genetic and environmental influences on covariation among two reading tests used in neuropsychological assessment (Cambridge Contextual Reading Test [CCRT], [Beardsall, L., and Huppert, F. A. (1994). J. Clin. Exp. Neuropsychol. 16:232-242], Schonell Graded Word Reading Test [SGWRT], [Schonell, F. J., and Schonell, P. E. (1960). Diagnostic and attainment testing. Edinburgh: Oliver and Boyd.]) and among a selection of IQ subtests from the Multidimensional Aptitude Battery (MAB), [Jackson, D. N. (1984). Multidimensional aptitude battery, Ontario: Research Psychologists Press.] and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) [Wechsler, D. (1981). Manual for the Wechsler Adult Intelligence Scale-Revised (WAIS-R). San Antonio: The Psychological Corporation]. Participants were 225 monozygotic and 275 dizygotic twin pairs aged from 15 years to 18 years (mean, 16 years). For Verbal IQ subtests, phenotypic correlations with the reading tests ranged from 0.44 to 0.65. For Performance IQ subtests, phenotypic correlations with the reading tests ranged from 0.23 to 0.34. Results of Structural Equation Modeling (SEM) supported a model with one genetic General factor and three genetic group factors (Verbal, Performance, Reading). Reading performance was influenced by the genetic General factor (accounting for 13% and 20% of the variance for the CCRT and SGWRT, respectively), the genetic Verbal factor (explaining 17% and 19% of variance for the CCRT and SGWRT), and the genetic Reading factor (explaining 21% of the variance for both the CCRT and SGWRT). A common environment factor accounted for 25% and 14% of the CCRT and SGWRT variance, respectively. Genetic influences accounted for more than half of the phenotypic covariance between the reading tests and each of the IQ subtests. The heritabilities of the CCRT and SGWRT were 0.54 and 0.65, respectively. Observable covariance between reading assessments used by neuropsychologists to estimate IQ and IQ subtests appears to be largely due to genetic effects.

Adolescent↗

PubMed2003

Local treatment of viral disease using photodynamic therapy.

Although reports of the photodynamic inactivation of viruses appeared in 1928, long before chemotherapeutic antiviral drugs, the first clinical trial in humans-the topical treatment of herpes genitalis-did not take place until the early 1970s. Trials were discontinued due to the transformation of healthy cells and concomitant incidence of Bowen's disease in some patients, probably due to the migration of infective sections of photodamaged viral nucleic acid. With the modern development of photodynamic therapy as a cancer treatment and the use of photosensitisers in the photodecontamination of blood products, a great deal of experience has been gained, both in the minimisation of side effects in humans and in the targeting and eradication of viruses. This suggests that the photodynamic approach to a range of virus-associated infections, lesions and cancer might now be revisited with greater success.

Humans↗

PubMed2003

Quinoline and cyanine dyes--putative anti-MRSA drugs.

One way in which drug-resistant bacteria may be attacked is to screen new series of candidate compounds. Quaternary quinoline compounds and dyes were studied by Carl Browning (1887-1972) and Julius Cohen (1859-1935). A remarkable part of Browning and Cohen's work was the early development of structure-activity relationships for their series of compounds. Thus cationic species were found generally to be more effective antibacterials than neutrals or anionics, and the testing of partial or deconstructed active molecules was also carried out. Much of this work underpinned the fuller understanding of e.g. aminoacridine action developed by Adrien Albert (1907-1989), himself also a collaborator of Browning. Analysis of the activity of a range of compounds developed by Browning and Cohen suggests that these might again be examined as topical antimicrobials in the fight against methicillin-resistant S. aureus (MRSA) and other resistant bacteria.

Anti-Bacterial Agents↗

PubMed2002

The emerging chemistry of blood product disinfection.

Given the importance and limitations of the blood supply worldwide, widely applicable procedures for the inactivation of pathogens (viruses, bacteria, protozoa etc.) in donated blood and blood products are now required. Conventional treatments such as ultraviolet irradiation cause damage to therapeutic components in the blood, so more targeted approaches are being sought. These include targeted chemotherapy, photochemotherapy and photodynamic antimicrobial chemotherapy (PACT).

Biological Products↗

PubMed2002

Pathogen inactivation in blood products.

A combination of the economic importance of blood as a resource and the advent of the AIDS epidemic has led to a requirement for improved pathogen screening techniques for donated blood. However, due to window periods where infective agents cannot be detected, the ability to disinfect of blood and its derivatives plasma, platelets and red blood cell concentrates has assumed great importance. Whereas conventional disinfection techniques such as solvent-detergent treatment or ultra-violet irradiation may be employed in plasma or protein concentrates, the collateral damage associated with such treatments disallows their use with cellular fractions. In many ways the pathogen selectivity required here is akin to standard antimicrobial chemotherapy but is complicated by the requirement for activity against the full range of microbes--viruses, bacteria, yeasts and protozoa--rather than simply antibacterial or antiviral etc. The recent problems due to prion agents in the blood supply mean that such agents should also be included in any proposed disinfecting regimen. Several new approaches to microbial disinfection have been proposed by academia and the "blood industrials" : targeted chemotherapy, photochemotherapy and photodynamic antimicrobial chemotherapy.

Animals↗