Photochemotherapeutic Strategy against Acanthamoeba Infections

Acanthamoeba is a protist pathogen that can cause serious human infections, including blinding keratitis and a granulomatous amoebic encephalitis that almost always results in death. The current treatment for these infections includes a mixture of drugs, and even then, a recurrence can occur. Photochemotherapy has shown promise in the treatment of Acanthamoeba infections; however, the selective targeting of pathogenic Acanthamoeba has remained a major concern. The mannose-binding protein is an important adhesin expressed on the surface membranes of pathogenic Acanthamoeba organisms. To specifically target Acanthamoeba, the overall aim of this study was to synthesize a photosensitizing compound (porphyrin) conjugated with mannose and test its efficacy in vitro. The synthesis of mannose-conjugated porphyrin was achieved by mixing benzaldehyde and pyrrole, yielding tetraphenylporphyrin. Tetraphenylporphyrin was then converted into mono-nitrophenylporphyrin by selectively nitrating the para position of the phenyl rings, as confirmed by nuclear magnetic resonance (NMR) spectroscopy. The mono-nitrophenylporphyrin was reduced to mono-aminophenylporphyrin in the presence of tin dichloride and confirmed by a peak at m/z 629. Finally, mono-aminoporphyrin was conjugated with mannose, resulting in the formation of an imine bond. Mannose-conjugated porphyrin was confirmed through spectroscopic analysis and showed that it absorbed light of wavelengths ranging from 425 to 475 nm. To determine the antiacanthamoebic effects of the derived product, amoebae were incubated with mannose-conjugated porphyrin for 1 h and washed 3 times to remove extracellular compound. Next, the amoebae were exposed to light of the appropriate wavelength for 1 h. The results revealed that mannose-conjugated porphyrin produced potent trophicidal effects and blocked excystation. In contrast, Acanthamoeba castellanii incubated with mannose alone and porphyrin alone did not exhibit an antiamoebic effect. Consistently, pretreatment with mannose-conjugated porphyrin reduced the A. castellanii-mediated host cell cytotoxicity from 97% to 4.9%. In contrast, treatment with porphyrin, mannose, or solvent alone had no protective effects on the host cells. These data suggest that mannose-conjugated porphyrin has application for the targeted photodynamic therapy of Acanthamoeba infections and may serve as a model in the development of therapeutic interventions against other eukaryotic infections.     

Thermophysical and Mechanical Properties of Hardened Cement Paste with Microencapsulated Phase Change Materials for Energy Storage

In this research, structural-functional integrated cement-based materials were prepared by employing cement paste and a microencapsulated phase change material (MPCM) manufactured using urea-formaldehyde resin as the shell and paraffin as the core material. The encapsulation ratio of the MPCM could reach up to 91.21 wt%. Thermal energy storage cement pastes (TESCPs) incorporated with different MPCM contents (5%, 10%, 15%, 20% and 25% by weight of cement) were developed, and their thermal and mechanical properties were studied. The results showed that the total energy storage capacity of the hardened cement specimens with MPCM increased by up to 3.9-times compared with that of the control cement paste. The thermal conductivity at different temperature levels (35–36 °C, 55–56 °C and 72–74 °C) decreased with the increase of MPCM content, and the decrease was the highest when the temperature level was 55–56 °C. Moreover, the compressive strength, flexural strength and density of hardened cement paste decreased with the increase in MPCM content linearly. Among the evaluated properties, the compressive strength of TESCPs had a larger and faster degradation with the increase of MPCM content.     

A dysglycaemic effect of statins in diabetes: relevance to clinical practice?

In this issue of the journal, Erqou and colleagues (DOI 10.1007/s00125-014-3374-x) report, in a systematic review and meta-analysis of randomised trials, a very modest (1.3 mmol/mol or 0.12%) albeit significant increase in HbA_1c in patients with diabetes treated with statins, compared with control. Here, we discuss the clinical relevance of the findings. Given the overwhelming benefit of statins on cardiovascular outcomes in diabetes, current guidelines recommending statins for primary prevention in type 2 diabetes should not change, and any effect on microvascular risk is likely to be minimal. Of course, all patients recommended for statin treatment, whether they have diabetes or not, should now be warned of a slight potential for dysglycaemia on starting statins, but at the same time they should be told that very modest lifestyle improvement will help offset this dysglycaemia risk. Finally, we remind colleagues that nearly all drugs have side effects and we should not be surprised by this statin–dysglycaemia effect, which can be easily managed.