Tailored-BODIPY/Amphiphilic Cyclodextrin Nanoassemblies with PDT Effectiveness.

Amphiphilic cyclodextrins (aCDs) are an intriguing class of carrier systems which, recently, have been proposed to deliver porphyrinoids and anticancer drugs or combined dose of both for dual therapeutic applications. The design of nanoassemblies based on aCD and photosensitizers (PSs) aims to preserve the photodynamic therapy (PDT) efficacy of PS, reducing the tendency of PS to self-aggregate, without affecting the quantum yield of singlet oxygen (1O2) production, and, not less importantly, minimizing dark toxicity and reducing photosensitization effects. With this idea in mind, in this paper, we focus on nanoassemblies between a non-ionic aCD (SC6OH) and halo-alkyl tailored iodinated boron-dipyrromethenes (BODIPY) dye, a class of molecules which recently have been successfully proposed as a stimulating alternative to porphyrinoids for their high photodynamic efficacy. Nanoassemblies of BODIPY/aCD (BL01I@SC6OH) were prepared in different aqueous media by evaporation of mixed organic film of aCD and BODIPY, hydration, and sonication. The nanostructures were characterized, measuring their hydrodynamic diameter and ξ-potential and also evaluating their time-stability in biological relevant media. Taking advantage of emissive properties of the not-iodinated BODIPY analogue (BL01), nanoassemblies based on aCD and BL01 were investigated as model system to get insight on entanglement of BODIPY in the amphiphile in aqueous dispersion, pointing out that BODIPY is well-entrapped in monomeric form (τ ≅ 6.5 ns) within the colloidal carriers. Also morphology and fluorescence emission properties were elucidated after casting the solution on glass. BL01@SC6OH is easily detectable in cytoplasm of HCT116 cell lines, evidencing the remarkable intracellular penetration of this nanoassembly similar to free BODIPY. On the same cell lines, the photodynamically active assembly BL01I/aCD shows toxicity upon irradiation. Despite the fact that free BL01I is more PDT active than its assembly, aCD can modulate the cell uptake of BODIPY, pointing out the potential of this system for in vivo PDT application.

Pure optical nano-writing on light- switchable spiropyrans/merocyanine thin film.

We report optical writing at the nanometer scale of spin coated PMMA-spiropyran films. By using a near-field optical microscope, pure optical nano-writing with a resolution of 160 nm and writing speed of 0.4 µm/s was achieved. Simultaneous topographic and optical writing was also obtained by simply coupling to the near-field few more mW of laser power. Due to the fast optical response of the spiropyran molecule, nano-lithography on PMMA-spyropyran thin films appears to be very attractive for future photonics applications.

Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature.

BACKGROUND: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation. METHODS: Primary CD44⁺CD24⁻ breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques. RESULTS: Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44⁻CD24⁺ and showed tumorigenic abilities after injection in secondary mice. CD44⁻CD24⁺ CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs. CONCLUSION: Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.

Teriparatide increases the maturation of circulating osteoblast precursors.

UNLABELLED: This study shows that teriparatide promotes the circulating osteoblast (OB) precursor degree of maturation in patients affected by postmenopausal osteoporosis. INTRODUCTION: Anabolic treatment with teriparatide has proven effective for the therapy of postmenopausal osteoporosis and significantly reduces the risk of non-vertebral fragility fractures. The aim of this study was to investigate the effect of teriparatide on circulating OB precursors. METHODS: We evaluated by flow cytometry and real-time PCR the expression of OBs typical markers in peripheral blood mononuclear cells during treatment with teriparatide plus calcium and vitamin D, raloxifene plus calcium and vitamin D or calcium and vitamin D alone at various time points. Serum bone alkaline phosphatase and osteocalcin (OC) were measured as markers of bone turnover. RESULTS: Our results show that circulating OB precursors are more numerous and more immature in patients affected by fragility fractures than in osteoporotic patients without fractures. We also show that teriparatide treatment increases the expression of alkaline phosphatase and of OC in OB precursors; thus, it increases their degree of maturation. CONCLUSIONS: We suggest that teriparatide acts as anabolic agents also by promoting the maturation of OB precursors.

Real-time monitoring of the surface relief formation on azo-polymer films upon near-field excitation.

We use near-field optical microscopy to investigate the early state formation of photo-induced topographical structures on the free surface of azobenzene-containing polymers. The near-field technique is employed to monitor in real time the mass migration during the embossing of the surface of 50/50 copolymer films of polymethacrylate and polymethacrylate containing 3-methyl-4'-pentyloxy-azobenzene units. The dynamic of surface relief formation induced by light have been investigated as a function of the sample temperature. Furthermore, a formula derived from Navier-Stokes equations for classical laminar flow has been used to fit the mass displacement data during the embossing process. Excellent agreements between the experimental data and the fitting formula have been found for all the temperature considered.

Polarization-maintaining near-field optical probes.

We demonstrate that tapered optical fibre probes can be easily modified in the taper cone to realize an electric dipole producing a well-defined near-field polarized light. This novel structure is made of a Short-cut Double C-shaped probe design combined to the usual full metal coating near the tapered end of the fibre. Hence, the cone at the apex of the probe is excited by an equivalent dipole whose spatial orientation is dictated by the probe geometry, regardless the polarization state of the incoming light. Properties and performances of such a configuration are first predicted by a finite-difference time domain simulation, showing that the near field coming out from the probe is linearly polarized. Following this novel design, a probe prototype is manufactured and tested. Its measured polar diagram confirms the polarization maintenance property in the near field.

Wide angle near-field optical probes by reverse tube etching.

We present a simple modification of the tube etching process for the fabrication of fiber probes for near-field optical microscopy. It increases the taper angle of the probe by a factor of two. The novelty is that the fiber is immersed in hydrofluoric acid and chemically etched in an upside-down geometry. The tip formation occurs inside the micrometer tube cavity formed by the polymeric jacket. By applying this approach, called reverse tube etching, to multimode fibers with 200/250 microm core/cladding diameter, we have fabricated tapered regions featuring high surface smoothness and average cone angles of approximately 30 degrees . A simple model based on the crucial role of the gravity in removing the etching products, explains the tip formation process.

Solution-deposited microstructures based on aluminum-tris-hydroxyquinoline.

Iridescent organic films consisting of quasi-parallel wire-like microstructures are grown by castings from ethanol solutions containing mixtures of aluminium-tris-hydroxyquinoline and 1,10-phenanthroline. Spectrophotometric measurements carried out in the ultraviolet-visible range indicate that the microstructured films have angular-dependent optical behaviour, which is motivated by a refractive-index modulation over dimensions that are comparable to visible-light wavelengths. According to the results of investigations carried out by means of optical microscopy, atomic force microscopy (AFM), and scanning near-field optical microscopy (SNOM), the refractive-index modulation originates from a thickness modulation and a phase separation that occurs as the aluminium-tris-hydroxyquinoline and phenanthroline co-crystallize, with the former material being arranged to form a green luminescent pattern on the top of the latter one.

A versatile multipurpose scanning probe microscope.

A combined scanning probe microscope has been developed that allows simultaneous operation as a non-contact/tapping mode atomic force microscope, a scattering near-field optical microscope, and a scanning tunnelling microscope on conductive samples. The instrument is based on a commercial optical microscope. It operates with etched tungsten tips and exploits a tuning fork detection system for tip/sample distance control. The system has been tested on a p-doped silicon substrate with aluminium depositions, being able to discriminate the two materials by the electrical and optical images with a lateral resolution of 130 nm.

Near-field Raman imaging of morphological and chemical defects in organic crystals with subdiffraction resolution.

In this study we report on the application of an aperture near-field optical microscope for Raman imaging of organic materials. Spectral analysis and detailed Raman imaging are performed with integration times of 100 ms per point, without the aid of field enhancement effects. The studied samples consist of two high Raman-efficiency molecular samples: a 7,7',8,8'-tetracyanoquinodimethane crystal showing surface defects and a 7,7',8,8'-tetracyanoquinodimethane thin film characterized by the presence of submicrometre-sized organometallic copper-salt complexes. In the first case, the effect of the surface deformation was studied, whereas in the second sample we were able to chemically image the formation of salt complexes. Subdiffraction resolution was achieved in both studies.

Morphologic variations in bacteria under stress conditions: near-field optical studies.

The morphologic and structural variations suffered by cells of a population of Pseudomonas aeruginosa ATCC 27853 under stress conditions were investigated by using scanning near-field optical microscopy. The analysis of the images, supported by microbiological data, showed that the bacteria evolved from the initial distribution of rod-shaped cells of standard size to a population with structural and morphologic modifications. The detection of variations in the optical reflectivity over a subwavelength scale (< or = 100 nm), combined with the concurrently acquired topographical signal, allowed the visualisation of rod-shaped bacteria going towards a lytic process and entire "U"-shaped cells. In the latter cells, which derived from a morphology refolding of rod bacteria, cellular matter seemed to rearrange itself to attain a coccoid stress resistant form, responsible for the residual viability of the population.

Optical near-field harmonic demodulation in apertureless microscopy.

Spatial derivatives of the optical fields scattered by a surface can be investigated by apertureless near-field optical microscopy by modulating sinusoidally the probe to sample distance and detecting the optical signal at the first and higher harmonics. Demodulation up to the fifth harmonic order has been accomplished on a sample of close-packed latex spheres by means of the silicon tip of a scanning interference apertureless microscope. The working principles of such microscope are reviewed. The experimental configuration used comprises a tuning-fork-based tapping-mode atomic force microscope for the distance stabilization, and a double-modulation technique for complete separation of the topography tracking from the optical detection. Simple modelling provides first indications for the interpretation of experimental data. The technique described here provides either artefact-free near-field optical imaging, or detailed information on the structure of the near fields scattered by a surface.

Arrhythmias during dipyridamole test. Report of 3 cases.

The authors report three cases in which the dipyridamole test provoked: (1) junctional rhythm with AV dissociation; (2) sinus arrest; (3) 2:1 AV block. The three cases described above draw attention to the possible effect of dipyridamole on the AV conduction, which is not yet completely known. This unwanted effect suggests that careful ECG monitoring should be performed during the dipyridamole test.

Modulated parasystole complicating permanent ventricular pacing: the different influence of spontaneous and paced impulses upon the parasystolic rhythm.

A case of modulated ventricular parasystole observed in a patient with a VVIM pacemaker is reported. Analysis reveals that the electronic influence (modulation) effected upon the parasystolic focus by the sinus impulses is different from that exerted by the paced impulses. Furthermore, fusion beats reflect an intermediate modulating effect according to the prevalence of the sinus or the paced wavefront.

Effects of calcitonin on morphine tolerance and withdrawal syndrome in morphine physically dependent rats.

We investigated the effect of acute or chronic peripheral administration of [Asu1.7]eel-calcitonin on the development of tolerance to the analgesic effect of morphine and on the naloxone-precipitated withdrawal syndrome in morphine-dependent rats. Neither the analgesic effect of acute morphine nor the development of tolerance to the antinociceptive effect of this drug was modified by calcitonin. However, the chronic but not the acute administration of calcitonin attenuated some signs and symptoms of morphine withdrawal.

[Effects of propafenone on arrhythmias induced by exertion in patients with ischemic cardiopathy]. / Effetti del propafenone sulle aritmie indotte dallo sforzo in pazienti con cardiopatia ischemica.

The efficacy of Propafenone to prevent exercise-induced ventricular arrhythmias (EIVA) has been studied in eleven patients affected by ischemic heart disease. None of the patients manifested any arrhythmia at rest, but ventricular arrhythmias occurred in every case during a treadmill test. EIVA disappeared after Propafenone in nine patients, while a reduction by 90% was achieved in the remaining two patients. A further treadmill test carried out five days after withdrawal of the drug induced again the same ventricular arrhythmias in all the patients. Thus, Propafenone appears effective to prevent EIVA in patients with ischemic heart disease.