The phototoxicity of aged human retinal melanosomes

The purpose of this study was to determine whether an age-related increase in photoreactivity of human retinal melanosomes (MS) can cause phototoxicity to retinal pigment epithelium (RPE) cells. MS were isolated post mortem from young (20-30 years, young human melanosomes [YHMs]) and old (60-90 years, old human melanosomes [OHMs]) human eyes and from young bovine eyes (bovine melanosomes [BMs]). Confluent cultured ARPE-19 cells were fed equivalent numbers of OHMs or BMs and accumulated similar amounts of melanin as determined by electron paramagnetic resonance assay. Cells with and without MS were either maintained in the dark or exposed to blue light for up to 96 h and assessed for alterations in cell morphology, cell viability and lysosomal integrity. Incubation of cells in dark in the presence of internalized MS or irradiation of cells with blue light in the absence or presence of BMs did not significantly affect cell viability. However, exposures to blue light in the presence of OHMs resulted in abnormal cell morphology, up to approximately 75% decrease in mitochondrial activity, loss of lysosomal pH and cell death. OHMs contained significantly less melanin than YHMs, supporting the hypothesis that melanin undergoes degradation during RPE aging. Our results demonstrate that aged MS can be phototoxic to human RPE cells and support a contributing role of MS in RPE aging and in the pathogenesis of age-related macular degeneration.     

On a class of non-self-adjoint periodic eigenproblems with boundary and interior singularities

We prove that all the eigenvalues of a certain highly non-self-adjoint Sturm-Liouville differential operator are real. The results presented are motivated by and extend those recently found by various authors (Benilov et al. (2003) [3], Davies (2007) [7] and Weir (2008) [18]) on the stability of a model describing small oscillations of a thin layer of fluid inside a rotating cylinder.     

A Convenient Synthesis of N-(α-Aminobenzyl)formamides

Three-component condensation of benzaldehyde, formamide, and morpholine or piperidine, results in an expeditious synthesis of the N-(α-dialkylaminobenzyl)-formamides.     

The separation by thin-layer chromatography of trace metals as their tetraphenylporphyrin chelates.

The tetraphenylporphyrin chelates of iron, cobalt, manganese, nickel, zinc, copper, rhodium lead, cadmium and mercury were prepared and their chromatographic behaviour investigated using four different adsorbents and eleven different solvent systems. Mixtures of lead, cadmium and mercury chelates exhibited isographic behaviour in all conditions; mixtures of the other metal chelates were adequately resolved on silica (MN Polygram Sil SHR) by the solvent system light petroleum (b.p. 80-100 degrees)-toluene-acetic acid-water (66:33:85:15, v/v, upper phase). The intense colours of the chelates permit their visual detection at levels of about 10(-10) moles; using the integrated ion-current mass spectrometric procedure, as little as 10(-14) moles of metal could be detected and assessed.     

Zinc-mediated intramolecular acyl and imino transfer reactions of aryl iodides

A method for the coupling of acyl and imino substituents to the sterically encumbered 5-position of a 4-aminoquinazoline was developed. Starting with a 4-amino-5-iodoquinazoline, the method employs a facile intramolecular zinc-mediated transfer from the 4-amino group to the iodo-bearing carbon. The method was found to be effective for a variety of substituents, in particular a pyridyl group required for the synthesis of Pfizer’s prostate selective α₁ antagonist candidate for the treatment of benign prostatic hyperplasia, UK-338,003.     

Synthesis of difunctional polystyrenes and their incorporation in block copolymers with bisphenol a polycarbonate

Block polymers of polystyrene and bisphenol A polycarbonate have been prepared and their bulk viscosities studied as functions of both shear stress and polystyrene block length. The polystyrene blocks were α,ω-diacid chlorides prepared from the reaction of “living” polystyrenes with diacid chlorides. These reactions were studied in order to discover the most effective way of preparing the polystyrene diacid chlorides. The polystyrene diacid chlorides are best prepared by reaction of disodiopolystyrene with phosgene. The flow properties of the block copolymers depend on the composition of the polymers but do not depend on the length of the polystyrene blocks.     

A Novel Application of Indocyanine Green Immunofluorescence in Emergent Colorectal Surgery

Here, we report on the feasibility of ICG fluorescence imaging to localize lesions in emergent minimally invasive surgery. A 49-year old female presented to the emergency department with a previously unknown malignant bowel obstruction. She was taken emergently to the operating room for a laparoscopic extended right hemicolectomy, based on tumor location from imaging. With intraoperative difficulty localizing the lesion, an on-table colonoscopy was performed. When the tumor was encountered, peritumoral ICG injections were performed, and the fluorescence lymphoscintigraphy was performed intraoperatively in an attempt to visualize the primary tumor laparoscopically. Intraoperative ICG Immunofluorescence allowed precise, real-time localization of the mass in the descending colon. This information changed the course of the operation, as a laparoscopic left hemicolectomy was then performed instead of the planned extended right hemicolectomy. The patient underwent an end-to-end anastomosis without the need for a defunctioning ileostomy. From this case, we demonstrate the use of ICG fluorescence imaging for tumor localization in the emergent setting is safe, feasible, and effective. This information gained from this technology enables real-time decision making, and can even change the operative plan in the emergent setting for the best patient outcomes. What does this paper add to the existing literature? This paper offers a novel application of an emerging technology- ICG fluorescence- that in this capacity allowed precise, real-time localization of a previously unknown mass in the emergent setting, and changed the course of the operation.     

HFO-1234yf as a CF3 Building Block: Synthesis of Trifluoromethyl Quinoline and Chromene Derivatives from Trifluoromethyl-ynones

Trifluoromethyl ynones derived from the refrigerant gas HFO-1234yf (2,3,3,3-tetrafluoropropene) react with nucleophiles via a Michael-type addition process and the allenolate intermediate formed reacts intramolecularly with a carbonyl group to form heterocyclic derivatives. Thus, reaction of 2-amino and 2-hydroxyl benzaldehyde or ketone substrates with trifluoromethyl ynone derivatives gives trifluoromethyl quinoline and chromene products by a one-pot tandem ring closing sequence, forming pharmaceutically relevant structures from an inexpensive starting material without the need for transition metals or column chromatography. The 2-trifluoromethylquinoline products also show unusual fluxional behaviour, which was explored through 2-D NMR and X-ray crystallographic studies.     

Concentration Dependence of Vitamin C in Combinations with Vitamin E and Zeaxanthin on Light‐Induced Toxicity to Retinal Pigment Epithelial Cells

The purpose of this study was to determine the effects of increasing concentration of ascorbate alone and in combinations with α‐tocopherol and zeaxanthin on phototoxicity to the retinal pigment epithelium. ARPE‐19 cells were exposed to rose bengal and visible light in the presence and absence of antioxidants. Toxicity was quantified by an assay of cell‐reductive activity. A 20 min exposure to visible light and photosensitizer decreased cell viability to ca 42%. Lipophilic antioxidants increased viabilities to ca 70%, 61% and 75% for α‐tocopherol, zeaxanthin and their combination, respectively. Cell viabilities were ca 70%, 56% and 5% after exposures in the presence of 0.35, 0.7 and 1.4 mm ascorbate, respectively. A 45 min exposure increased cell death to ca 74% and >95% in the absence and presence of ascorbate, respectively. In the presence of ascorbate, zeaxanthin did not significantly affect phototoxicity. α‐Tocopherol and its combination with zeaxanthin enhanced protective effects of ascorbate, but did not prevent from ascorbate‐mediated deleterious effects. In conclusion, there is a narrow range of concentrations and exposure times where ascorbate exerts photoprotective effects, exceeding which leads to ascorbate‐mediated increase in photocytotoxicity. Vitamin E and its combination with zeaxanthin can enhance protective effects of ascorbate, but do not ameliorate its deleterious effects.