Photosensitisers - the progression from photodynamic therapy to anti-infective surfaces

Introduction: The application of light as a stimulus in pharmaceutical systems and the associated ability to provide precise spatiotemporal control over location, wavelength and intensity, allowing ease of external control independent of environmental conditionals, has led to its increased use. Of particular note is the use of light with photosensitisers.

Areas covered: Photosensitisers are widely used in photodynamic therapy to cause a cidal effect towards cells on irradiation due to the generation of reactive oxygen species. These cidal effects have also been used to treat infectious diseases. The effects and benefits of photosensitisers in the treatment of such conditions are still being developed and further realised, with the design of novel delivery strategies. This review provides an overview of the realisation of the pharmaceutically relevant uses of photosensitisers, both in the context of current research and in terms of current clinical application, and looks to the future direction of research.

Expert opinion: Substantial advances have been and are being made in the use of photosensitisers. Of particular note are their antimicrobial applications, due to absence of resistance that is so frequently associated with conventional treatments. Their potency of action and the ability to immobilise to polymeric supports is opening a wide range of possibilities with great potential for use in healthcare infection prevention strategies.

A European Culture War in the Twentieth Century? Antic-Catholicism and Anti-Bolshevism between Moscow, Berlin, and the Vatican 1922 to 1933

The term “culture war” has become a generic expression for secular-catholic conflicts across nineteenth-century Europe. Yet, if measured by acts of violence, anticlericalism peaked in the years between 1927 and 1939, when thousands of Catholic priests and believers were imprisoned or executed and hundreds of churches razed in Mexico, Spain and Russia. This essay argues that not only in these three countries, but indeed across Europe a culture war raged in the interwar period. It takes, as a case study, the interaction of communist and Catholic actors located in the Vatican, the Soviet Union, and Germany in the period between the beginning of the Pontificate of Pius XI in 1922 and Hitler’s appointment as chancellor of Germany in 1933. Using correspondence and reports from the Vatican archives, this essay shows how Papal officials and communist leaders each sought to mobilize the German populace to achieve their own diplomatic ends. German Catholics and communists gladly responded to the call to arms that sounded from Rome and Moscow in 1930, but they did so also to further their own domestic goals. The case study shows how national contexts inflected the transnational dynamics of radical anti-Catholicism in interwar Europe. In the end, agitation against “godlessness” did not lead to the return of a “Christian State” desired by many conservative Christians. Instead, the culture war further destabilized the republic and added a religious dimension to a landscape well suited to National Socialist efforts to reach a Christian population otherwise mistrustful of its völkisch and anticlerical elements.

In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine

Background: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. Five species of Schistosoma are known to infect humans, out of which S. haematobium is the most prevalent, causing the chronic parasitic disease schistosomiasis that still represents a major problem of public health in many regions of the world and especially in tropical areas, leading to serious manifestations and mortality in developing countries. Since the 1970s, praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis, but concerns about relying on a single drug to treat millions of people, and the potential appearance of drug resistance, make identification of alternative schistosomiasis chemotherapies a high priority. Alkylphospholipid analogs (APLs), together with their prototypic molecule edelfosine (EDLF), are a family of synthetic antineoplastic compounds that show additional pharmacological actions, including antiparasitic activities against several protozoan parasites.

Methodology/Principal Findings: We found APLs ranked edelfosine> perifosine> erucylphosphocholine> miltefosine for their in vitro schistosomicidal activity against adult S. mansoni worms. Edelfosine accumulated mainly in the worm tegument, and led to tegumental alterations, membrane permeabilization, motility impairment, blockade of male-female pairing as well as induction of apoptosis-like processes in cells in the close vicinity to the tegument. Edelfosine oral treatment also showed in vivo schistosomicidal activity and decreased significantly the egg burden in the liver, a key event in schistosomiasis.

Conclusions/Significance: Our data show that edelfosine is the most potent APL in killing S. mansoni adult worms in vitro. Edelfosine schistosomicidal activity seems to depend on its action on the tegumental structure, leading to tegumental damage, membrane permeabilization and apoptosis-like cell death. Oral administration of edelfosine diminished worm and egg burdens in S. mansoni-infected CD1 mice. Here we report that edelfosine showed promising antischistosomal properties in vitro and in vivo.

A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation

Elafin is a serine protease inhibitor produced by epithelial and immune cells with anti-inflammatory properties. Research has shown that dysregulated protease activity may elicit proteolytic cleavage of elafin, thereby impairing the innate immune function of the protein. The aim of this study was to generate variants of elafin (GG- and QQ-elafin) that exhibit increased protease resistance while retaining the biological properties of wild-type (WT) elafin. Similar to WT-elafin, GG- and QQ-elafin variants retained antiprotease activity and susceptibility to transglutaminase-mediated fibronectin cross-linking. However, in contrast to WT-elafin, GG- and QQ-elafin displayed significantly enhanced resistance to degradation when incubated with bronchoalveolar lavage fluid from patients with cystic fibrosis. Intriguingly, both variants, particularly GG-elafin, demonstrated improved lipopolysaccharide (LPS) neutralization properties in vitro. In addition, GG-elafin showed improved anti-inflammatory activity in a mouse model of LPS-induced acute lung inflammation. Inflammatory cell infiltration into the lung was reduced in lungs of mice treated with GG-elafin, predominantly neutrophilic infiltration. A reduction in MCP-1 levels in GG-elafin treated mice compared to the LPS alone treatment group was also demonstrated. GG-elafin showed increased functionality when compared to WT-elafin and may be of future therapeutic relevance in the treatment of lung diseases characterized by a protease burden.

Short comment: To Nail a Jellyfish? Finding a progressive agenda for EU anti-discrimination law

The title of this short (about 4500 words) intervention translates to "To Nail a Jellyfish? Finding a progressive agenda for EU anti-discrimination law". I engage with those criticising EU anti-discrimination law as yet another emanation of the EU's "neo-liberal" nature which fails to establish a viable social policy regime. I criticise this in two directions. First, I take issue with the theory that anti-discrimination law and policy has to be part of social policy. Actually, the field has a mission which differs from social policy, in that it addresses disadvantage resulting from othering, combating stereotypes as well as promoting accomodation of difference. Second, I show how the critique of judicialisation of policy is not unique to anti-discrimination law and policy. The so called turn to rights based employment law has been criticised under this mantra by those who fear that collective labour law mechanisms will become less prevalent. Further, those who have engaged with anti-discrimination law for a much longer time than those criticising it have also devised means to overcome the individualistic tendencies of rights adjudication. They have (partly successfully) argued in favour of establishing equality bodies and creating positive obligations. Thus, the critique neglects the field it takes on, and does not accept the fact that anti-discrimination law and policy must be considered a field in its own right instead of the servant of social law and policy.
Now, this is more a summary than an abstract - since I realise that not everyone reads German.

The anti-atherogenic effects of eicosapentaenoic and docosahexaenoic acid are dependent on the stage of THP-1 macrophage differentiation.

In this study LC n-3 PUFA-specific effects on the degree of monocyte differentiation and macrophage foam cell formation were investigated by treating PMA-induced immature and mature macrophage models with LC n-3/n-6 PUFA during and post-differentiation. During immature macrophage differentiation LC n-3 PUFA alone decreased TNFα mRNA levels. EPA, and the n-6 PUFAs, linoleic acid and arachidonic acid, decreased CD36 mRNA levels, and EPA also downregulated CD49d cell-surface expression. Both LC n-3 PUFA reduced LDLr mRNA levels in immature macrophages, while DHA alone reduced levels in mature macrophages. Post-differentiation, n-3 and -6 PUFA reduced basal, but not oxidised LDL dependent cholesterol levels in immature macrophages. LC n-3 PUFA-specific reductions in LDLr and LOX-1 mRNA expression were also observed.

This study found LC n-3 PUFA specific, anti-atherogenic effects were more significant in immature macrophages. LC n-3 PUFA effects may be modulated by the extent of monocyte to macrophage differentiation.

The application of Raman and anti-stokes Raman spectroscopy for in situ monitoring of structural changes in laser irradiated titanium dioxide materials

The use of Raman and anti-stokes Raman spectroscopy to investigate the effect of exposure to high power laser radiation on the crystalline phases of TiO₂ has been investigated. Measurement of the changes, over several time integrals, in the Raman and anti-stokes Raman of TiO₂ spectra with exposure to laser radiation is reported. Raman and anti-stokes Raman provide detail on both the structure and the kinetic process of changes in crystalline phases in the titania material. The effect of laser exposure resulted in the generation of increasing amounts of the rutile crystalline phase from the anatase crystalline phase during exposure. The Raman spectra displayed bands at 144 cm^-1 (A1g), 197 cm^-1 (Eg), 398 cm^-1 (B1g), 515 cm^-1 (A1g), and 640 cm^-1 (Eg) assigned to anatase which were replaced by bands at 143 cm^-1 (B1g), 235 cm^-1 (2 phonon process), 448 cm^-1 (Eg) and 612 cm^-1 (A1g) which were assigned to rutile. This indicated that laser irradiation of TiO₂ changes the crystalline phase from anatase to rutile. Raman and anti-stokes Raman are highly sensitive to the crystalline forms of TiO₂ and allow characterisation of the effect of laser irradiation upon TiO₂. This technique would also be applicable as an in situ method for monitoring changes during the laser irradiation process