Highly porous phosphate-based glasses for controlled delivery of antibacterial Cu ions prepared via sol-gel chemistry.

Mesoporous glasses are a promising class of bioresorbable biomaterials characterized by high surface area and extended porosity in the range of 2 to 50 nm. These peculiar properties make them ideal materials for the controlled release of therapeutic ions and molecules. Whilst mesoporous silicate-based glasses (MSG) have been widely investigated, much less work has been done on mesoporous phosphate-based glasses (MPG). In the present study, MPG in the P2O5-CaO-Na2O system, undoped and doped with 1, 3, and 5 mol% of Cu ions were synthesized via a combination of the sol-gel method and supramolecular templating. The non-ionic triblock copolymer Pluronic P123 was used as a templating agent. The porous structure was studied via a combination of Scanning Electron Microscopy (SEM), Small-Angle X-ray Scattering (SAXS), and N2 adsorption-desorption analysis at 77 K. The structure of the phosphate network was investigated via solid state 31P Magic Angle Spinning Nuclear Magnetic Resonance (31P MAS-NMR) and Fourier Transform Infrared (FTIR) spectroscopy. Degradation studies, performed in water via Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), showed that phosphates, Ca2+, Na+ and Cu ions are released in a controlled manner over a 7 days period. The controlled release of Cu, proportional to the copper loading, imbues antibacterial properties to MPG. A significant statistical reduction of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacterial viability was observed over a 3 days period. E. coli appeared to be more resistant than S. aureus to the antibacterial effect of copper. This study shows that copper doped MPG have great potential as bioresorbable materials for controlled delivery of antibacterial ions.

Invasive Fish and Sea Urchins Drive the Status of Canopy Forming Macroalgae in the Eastern Mediterranean.

Canopy-forming macroalgae, such as Cystoseira sensu lato, increase the three-dimensional complexity and spatial heterogeneity of rocky reefs, enhancing biodiversity and productivity in coastal areas. Extensive loss of canopy algae has been recorded in recent decades throughout the Mediterranean Sea due to various anthropogenic pressures. In this study, we assessed the biomass of fish assemblages, sea urchin density, and the vertical distribution of macroalgal communities in the Aegean and Levantine Seas. The herbivore fish biomass was significantly higher in the South Aegean and Levantine compared to the North Aegean. Very low sea urchin densities suggest local collapses in the South Aegean and the Levantine. In most sites in the South Aegean and the Levantine, the ecological status of macroalgal communities was low or very low at depths deeper than 2 m, with limited or no canopy algae. In many sites, canopy algae were restricted to a very narrow, shallow zone, where grazing pressure may be limited due to harsh hydrodynamic conditions. Using Generalized Linear Mixed Models, we demonstrated that the presence of canopy algae is negatively correlated with the biomass of the invasive Siganus spp. and sea urchins. The loss of Cystoseira s.l. forests is alarming, and urgent conservation actions are needed.

Silver-doped phosphate coacervates to inhibit pathogenic bacteria associated with wound infections: an in vitro study.

There is a great demand from patients requiring skin repair, as a result of poorly healed acute wounds or chronic wounds. These patients are at high risk of constant inflammation that often leads to life-threatening infections. Therefore, there is an urgent need for new materials that could rapidly stimulate the healing process and simultaneously prevent infections. Phosphate-based coacervates (PC) have been the subject of increased interest due to their great potential in tissue regeneration and as controlled delivery systems. Being bioresorbable, they dissolve over time and simultaneously release therapeutic species in a continuous manner. Of particular interest is the controlled release of metallic antibacterial ions (e.g. Ag+), a promising alternative to conventional treatments based on antibiotics, often associated with antibacterial resistance (AMR). This study investigates a series of PC gels containing a range of concentrations of the antibacterial ion Ag+ (0.1, 0.3 and 0.75 mol%). Dissolution tests have demonstrated controlled release of Ag+ over time, resulting in a significant bacterial reduction (up to 7 log), against both non-AMR and AMR strains of both Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa). Dissolution tests have also shown controlled release of phosphates, Ca2+, Na+ and Ag+ with most of the release occurring in the first 24 h. Biocompatibility studies, assessed using dissolution products in contact with human keratinocyte cells (HaCaT) and bacterial strains, have shown a significant increase in cell viability (p ≤ 0.001) when gels are dissolved in cell medium compared to the control. These results suggest that gel-like silver doped PCs are promising multifunctional materials for smart wound dressings, being capable of simultaneously inhibit pathogenic bacteria and maintain good cell viability.

Identification of Antimicrobial Compounds in Two Streptomyces sp. Strains Isolated From Beehives.

The World Health Organization warns that the alarming increase in antibiotic resistant bacteria will lead to 2.7 million deaths annually due to the lack of effective antibiotic therapies. Clearly, there is an urgent need for short-term alternatives that help to alleviate these alarming figures. In this respect, the scientific community is exploring neglected ecological niches from which the prototypical antibiotic-producing bacteria Streptomycetes are expected to be present. Recent studies have reported that honeybees and their products carry Streptomyces species that possess strong antibacterial activity. In this study, we have investigated the antibiotic profile of two Streptomycetes strains that were isolated from beehives. One of the isolates is the strain Streptomyces albus AN1, which derives from pollen, and shows potent antimicrobial activity against Candida albicans. The other isolate is the strain Streptomyces griseoaurantiacus AD2, which was isolated from honey, and displays a broad range of antimicrobial activity against different Gram-positive bacteria, including pathogens such as Staphylococcus aureus and Enterococus faecalis. Cultures of S. griseoaurantiacus AD2 have the capacity to produce the antibacterial compounds undecylprodigiosin and manumycin, while those of S. albus AN1 accumulate antifungal compounds such as candicidins and antimycins. Furthermore, genome and dereplication analyses suggest that the number of putative bioactive metabolites produced by AD2 and AN1 is considerably high, including compounds with anti-microbial and anti-cancer properties. Our results postulate that beehives are a promising source for the discovery of novel bioactive compounds that might be of interest to the agri-food sector and healthcare pharmaceuticals.

Antibacterial Copper-Doped Calcium Phosphate Glasses for Bone Tissue Regeneration.

Calcium phosphate glasses are a promising new generation of biomaterials that can simultaneously induce tissue regeneration and controlled release of therapeutic molecules. In this work, novel calcium phosphate glasses containing 0, 2, 4, and 6 mol % Cu2+ were synthesized via room temperature precipitation reaction in aqueous solution. The effect of Cu2+ addition on the glass properties and structure was investigated using thermal analysis, 31P solid-state MAS NMR, Raman spectroscopy, and X-ray diffraction. All glasses crystallize at temperature >500 °C and are mainly formed by Q1 groups. The release of P, Ca, and Cu in solution over time was monitored via inductively coupled plasma-optical emission spectroscopy. It was found that with increasing Cu content, the amount of P and Ca released decreases whereas the amount of Cu released increases. The effect of Cu2+ release on the antibacterial activity against S. aureus, a bacterial strain commonly found in postsurgery infections, has been investigated. The addition of copper has been shown to infer the glasses antibacterial properties. As expected, the antibacterial activity of the glasses increases with increasing Cu2+ content. Cytocompatibility was assessed by seeding human osteoblast-like osteosarcoma cells Saos-2 (HTB85) on the glass particles. A significant increase in cell number was observed in all the glasses investigated. The copper-doped calcium phosphate glasses have proven to be multifunctional, as they combine bone regenerative properties with antibacterial activity. Therefore, they have great potential as antibacterial bioresorbable materials for hard tissue regeneration.

Snake venom poisoning in Greece. Experiences with 147 cases.

BACKGROUND: Snake venom poisoning is a medical emergency requiring immediate attention. Bites from poisonous European snakes can lead to local tissue damage and systemic symptoms. Vipera ammodytes accounts for the most envenomation in Greece. METHODS: The demographic and epidemiological characteristics, clinical symptoms and signs, laboratory findings, treatment, and outcome of 147 consecutive victims of V. ammodytes admitted to our hospital from 1988 to 2003 were reviewed and analyzed. RESULTS: The most common symptoms and signs included fang marks (100%), pain (100%), swelling (98.64%), ecchymosis (60.54%), tachycardia (32.65%), fainting or dizziness (29.93%), fever (23.13%), enlargement of regional lymph nodes (17.69%), nausea (16.33%), hypotension (13.61%), and vomiting (12.93%). The main complications were reduced range of motion, thrombophlebitis, local hemorrhagic blister formation, skin bleeding, rhabdomyolysis, reduced sensation, acute renal failure, necrosis with tissue loss, carpal tunnel syndrome, compartment syndrome, Kounis syndrome, and digit amputation. CONCLUSIONS: A V. ammodytes bite is a potentially serious event that requires immediate hospital care. Yet, the majority of victims can be treated successfully with conservative methods. No deaths occurred in our series.

The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal.

PURPOSE: To define the risk of hydroxychloroquine (HCQ)-related retinal toxicity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who are receiving recommended dosages of the drug (< or =6.5 mg/kg/day). DESIGN: Prospective cohort study, from 1985 to 2000. PARTICIPANTS: Greek patients with RA (n = 335) and SLE (n = 191) treated with HCQ, 400 of whom had completed at least 6 years of treatment. METHODS: Ophthalmologic evaluation was performed every 6 months from 1985 to 1995, and yearly thereafter. This consisted of best-corrected visual acuity, color vision testing, static central visual field testing, fundoscopy, electroretinography, and fluorescein angiography, when indicated. MAIN OUTCOME MEASURES: Fundus lesions attributed to HCQ. RESULTS: No HCQ retinal toxicity was noted in any of the 526 patients during the first 6 years of treatment. Two (3.4%) of the first 58 long-term (>6 years) treated patients developed HCQ-related maculopathy at 8 and 6.5 years of treatment, despite regular ophthalmologic evaluation. On follow-up 7 and 9 years after cessation of HCQ treatment, both patients had stable eye disease. No HCQ retinal toxicity was observed in the subsequent 342 patients who were treated for >6 years. Overall, the incidence of HCQ-related retinopathy in 400 patients who were treated with recommended dosages of the drug for a mean of 8.7 years was reduced to 0.5%. CONCLUSIONS: After a baseline ophthalmic examination to confirm the absence of preexisting fundus pathology, patients with normal renal function may receive HCQ at a maximal daily dosage of 6.5 mg/kg and continue safely for 6 years. However, annual screening is recommended in patients who have taken the drug, even in recommended doses, for >6 years.