Synthesis of some novel dimethine, bis-dimethine cyanine dyes and octacosamethine cyanine dyes endowed with promising biological potency against (HepG2), (Hela), (MCF-7), (MIA), (SN12C) and (H358) cell lines.

Successfully, one step two component synthesis of dimethine cyanine dyes, bis-dimethine cyanine dyes and icosamethine cyanine dyes 2-10via reaction of pyridinium salt 1 with some different aldehydes hope to obtain these compounds with enhanced biological potency as antitumor agents against spontaneous liver (HepG2), cervical (Hela), breast (MCF-7), pancreas (MIA), kidney (SN12C) and lung (H358). The impact of substituted drugs on the tumor cells was reflected by means of structure activity relationship (SAR). Among these dyes, icosamethine cyanine dye 8 recorded an excellent activity toward all the tested cell lines. The newly destined drugs were identified and emphasized by spectroscopy and elemental analyses.

PREPARATION OF B-CYCLODEXTRIN-THIABENDAZOLE-PIPERONYL BUTOXIDE SUPRAMOLECULAR COMPLEX AND ITS ACTIVITY AGAINST BLUE AND GREEN MOULD DECAY ON INOCULATED SATSUMA FRUIT.

The supramolecular complex of ß-cyclodextrin-thiabendazole-piperony butoxide (ßCD-TBZ/PBO) was prepared and its structure was characterized by 1H NMR. Additionally, the antifungal activity of ßCD-TBZ/PBO was investigated in comparison with the commercially available thiabendazole (TBZ) fungicide by in vitro tests and on artificially inoculated 'Okitsu' satsuma fruit dipped in water at 20 degrees C or at 50 degrees C to control postharvest blue (Penicillium italicum) and green mould (P. digitatum). ß-CD-TBZ/PBO is stable for several months when stored as powder in a dark bottle. At pH 7.0 the water solubility of the ßCD-TBZ/PBO complex was consistently higher than free TBZ. Water dip at 20 degrees C did not affect decay incidence caused by blue mould but favoured the development of green mould during 4-8 days of storage at 20 degrees C with respect to untreated (control) fruit. Water at 50 degrees C effectively reduced the incidence of blue mould and totally suppressed green mould during the first 4 days but lost its efficacy afterwards. By contrast, both TBZ and ßCD-TBZ/PBO had a lasting effect and were equally effective in controlling green and blue mould decay when applied at 20 degrees C and 60 mg L(-1) active ingredient (a.i.). When applied at 50 degrees C and 20 mg L(-1) a.i. the activity of the complex against blue mould was inferior than the corresponding treatment with TBZ. In vitro assays revealed a significant effectiveness of ßCD-TBZ/PBO complex at low concentration compared to commercial formulation of TBZ.

Effect of different film packaging on microbial growth in minimally processed cactus pear (Opuntia ficus-indica).

Microorganisms are natural contaminants of fresh produce and minimally processed products, and contamination arises from a number of sources, including the environment, postharvest handling and processing. Fresh-cut products are particularly susceptible to microbial contaminations because of the changes occurring in the tissues during processing. In package gas composition of modified atmosphere packaging (MAP) in combination with low storage temperatures besides reducing physiological activity of packaged produce, can also delay pathogen growth. Present study investigated on the effect of MAPs, achieved with different plastic films, on microbial growth of minimally processed cactus pear (Opuntio ficus-indica) fruit. Five different plastic materials were used for packaging the manually peeled fruit. That is: a) polypropylene film (Termoplast MY 40 micron thickness, O2 transmission rate 300 cc/m2/24h); b) polyethylene film (Bolphane BHE, 11 micron thickness, O2 transmission rate 19000 cc/m2/24h); c) polypropylene laser-perforated films (Mach Packaging) with 8, 16 or 32 100-micron holes. Total aerobic psychrophilic, mesophilic microorganisms, Enterobacteriaceae, yeast, mould populations and in-package CO2, O2 and C2H4 were determined at each storage time. Different final gas compositions, ranging from 7.8 KPa to 17.1 KPa O2, and 12.7 KPa to 2.6 KPa CO2, were achieved with MY and micro perforated films, respectively. Differences were detected in the mesophilic, Enterobacteriaceae and yeast loads, while no difference was detected in psychrophilic microorganisms. At the end of storage, microbial load in fruits sealed with MY film was significantly lower than in those sealed with BHE and micro perforated films. Furthermore, fruits packed with micro-perforated films showed the highest microbial load. This occurrence may in part be related to in-package gas composition and in part to a continuous contamination of microorganisms through micro-holes.

Effect of heat treatments on biomolecular profile of Sardinian apple cultivars.

Postharvest heat treatments (hot water or hot air treatment) may be applied to horticultural crops to control fungal diseases, insect infestation and to reduce chilling injury in cultivars susceptible to low storage temperatures. The present study investigated the influence of hot water (53 degrees C for 60s) and hot air treatment (38 degrees C for 24h) applied to two typical Sardinian apple varieties, cvs. Miali and Caddina, on the composition of the lipophilic extracts of the peel as well as on the antioxidant activity of ethanolic extracts of both peel and pulp. The lipophilic extracts of the peel of the two varieties were almost similar and resulted to be dominated by the presence of triterpenes being ursolic and oleanoic acids the main metabolites in both analysed fruits. The chemical analysis of the extracts obtained from the different heat-treated samples for each variety revealed no significant difference in the relative distribution of triterpene components with respect to untreated control samples. This strongly suggested that heat treatment does not affect the composition of terpene metabolite profile of the fruit peel. On the other hand, the antioxidant activity of the ethanolic extracts of the peel and the pulp of heat treated was significantly different from that of control In particular, on Caddina variety the antioxidant activity levels of the peel were consistently higher than in the pulp and were affected by storage conditions. Differently, on Miali variety the antioxidant activity of heat-treated samples was higher than control sample in both peel and pulp.

PERG adaptation for detection of retinal ganglion cell dysfunction in glaucoma: a pilot diagnostic accuracy study.

It has been previously demonstrated that the adaptive phase changes of steady-state pattern electroretinogram (SS-PERG), recorded during 4-min presentation of patterned stimuli, are reduced in glaucoma suspects and patients compared to normal subjects. Our study aims at testing the hypothesis that adaptive changes of SS-PERG, recorded using the novel optimized Next Generation PERG (PERGx) protocol, differ between glaucoma patients and controls. In this pilot cross-sectional study, we included 28 glaucoma patients and 17 age-matched normal subjects. Both patients and controls underwent a full ophthalmologic examination, visual field testing, OCT and PERGx. The PERGx signal was sampled over 2 min (providing 1 noise and 9 signal packets) in response to alternating gratings generated on an OLED display. PERGx amplitude and phase were analyzed to quantify adaptive changes over recording time. Receiver operating characteristic (ROC) curves were used to study the diagnostic accuracy of PERGx parameters in distinguishing glaucoma patients from normal subjects. PERGx amplitude and phase data showed declining trends in both groups. PERGx amplitude slope and grand-average vector amplitude and phase were significantly different in patients compared to controls (p < 0.01), whereas phase angular dispersion was greater in patients but not significantly different between the two groups. The area under the ROC curves were 0.87 and 0.76 for PERGx amplitude slope and grand-average vector amplitude, and 0.62 and 0.87 for PERGx angular dispersion and grand-average vector phase, respectively. The PERGx paradigm resulted highly accurate in detecting the reduction of amplitude adaptive changes in glaucoma patients, presumably due to the loss of functional retinal ganglion cell autoregulation. Thus, PERG adaptation, recorded by this new protocol, might be helpful in the identification and diagnosis of early glaucomatous dysfunction.

Synthesis, Characterization, and Biochemical Impacts of Some New Bioactive Sulfonamide Thiazole Derivatives as Potential Insecticidal Agents against the Cotton Leafworm, Spodoptera littoralis.

A novel series of anticipated biologically active heterocyclic compounds, such as pyrazole, thiazole, pyridine, acrylamide, thiophene, triazolo[1,5-a]pyrimidine, imidazolidine, aminopyrazole, pyrazolo[5,1-c][1,2,4]triazine, triazolo[4,3-a]pyrimidine, benzo[4,5]imidazo[1,2-a]pyrimidine, pyrido[2',3':3,4]pyrazolo[5,1-c][1,2,4]triazine, isoxazole, benzo[4,5]imidazo[2,1-c][1,2,4]triazine, pyrimidine, pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine, pyrano[2,3-d]pyrimidine, and chromene derivatives, incorporating a sulfonamide-bearing thiazole moiety suitable to utilize as insecticidal agents were synthesized via a versatile, readily accessible cyanoacetanilide, 2-cyano-N-(4-(N-(thiazol-2-yl)sulfamoyl)phenyl)acetamide (1).The structures of the newly synthesized compounds were elucidated by IR, MS, 1H NMR, 13C NMR, distortionless enhancement by polarization transfer (DEPT), 1H-1H correlation spectroscopy (COSY), heteronuclear multiple bond correlation (HMBC), and heteronuclear single quantum coherence (HSQC) spectral analysis. Toxicological and biochemical parameters and biological aspects of the demonstrated compounds of the synthesized products against the cotton leafworm, Spodoptera littoralis, under laboratory conditions were also investigated. Regarding the determined LC50 and LC90 values, sulfonamides bearing a thiazole moiety, 16a, 8, 28, and 31b, showed the most potent toxic effects with LC50 values of 49.04, 62.66, 78.62, and 94.90 ppm, respectively, and toxicity index of 100%, 78.26%, 62.38%, and 51.68%, respectively.

Same-day surgery may reduce the risk of losing pain perception in dogs with thoracolumbar disc extrusion.

OBJECTIVES: To compare the proportions of dogs with thoracolumbar disc extrusion that lose pelvic limb pain perception if surgery is performed on the day of admission or delayed overnight. To describe the outcome of those dogs that deteriorate to lose pain perception. MATERIALS AND METHODS: Retrospective, single centre study on 273 client-owned dogs with thoracolumbar disc extrusion and intact pain perception, but inability to walk unaided on their pelvic limbs. Dogs were subdivided into two groups: early surgery (spinal decompression between their examination at day of admission and the following morning), and delayed surgery (did not undergo surgery between admission and the following morning). The proportion of dogs that lost pelvic limb pain perception overnight was compared between the early and delayed surgery groups. RESULTS: Seven of 151 dogs in the early surgery group lost pain perception overnight compared to 15 of 122 in the delayed surgery group (Fisher's exact test, P = 0.025). Number-needed-to-treat analysis suggested that 14 dogs (95% confidence interval: 7-106 dogs) need early surgery to prevent one losing pain perception overnight. Five of the seven dogs that lost pain perception in the early surgery group recovered pain perception by 3 weeks post-operatively, compared to eight of 14 in the delayed group. CLINICAL SIGNIFICANCE: This study suggests that an overnight delay before spinal decompression increases the risk of clinically meaningful deterioration in dogs unable to walk following thoracolumbar disc extrusion.

Resveratrol proniosomes as a convenient nanoingredient for functional food.

Proniosomes are free-flowing powders composed of water-soluble carriers blended with surfactants, which form niosomes upon hydration. In this work, proniosomal formulations containing the natural antioxidant resveratrol (RSV) were prepared and fully characterized. A pre-formulation study on RSV-loaded niosomes was carried out to determine the most promising ratio between the two surfactants, Tween 20 and Span 60, in terms of entrapment efficiency and antioxidant activity. The optimized formulae were subsequently adapted to be prepared as proniosomes by the slurry method, including lactose or maltodextrin as carriers. The impact of surfactants and carriers properties on size, entrapment efficiency and release kinetics of proniosomes were evaluated. In vitro release of RSV in simulated gastric and intestinal media was determined, as well as the vesicular stability. Moreover, the biocompatibility of the formulations was determined on intestinal cells in vitro. Overall, the developed proniosomes provide promising nanoingredient for functional food, improving resveratrol stability and bioavailability.

Synthesis, antitumor evaluation, molecular modeling and quantitative structure-activity relationship (QSAR) of some novel arylazopyrazolodiazine and triazine analogs.

The synthesis, in vivo and in vitro antitumor evaluation, and QSAR studies of some novel pyrazole analogs against Ehrlich Ascites Carcinoma (EAC) cells were described. In vitro results revealed that compounds 10, 6 and 4 were the most potent analogs against EAC, respectively. Moreover, in vivo evaluation of compounds 6 and 10 proved their capability to normalize the blood picture in comparison to 5-FU, a well known anticancer drug. These novel pyrazole analogs were molecularly designed with the goal of having significant potent cytotoxic effect against EAC cells. To develop a QSAR model capable of identifying the key molecular descriptors associated with the biological activity of the novel pyrazole analogs and predicting the cytotoxic effect for other novel pyrazole analogs against EAC cells, different QSAR models, using different physicochemical and topological molecular descriptors, were developed. Different molecular descriptors were predicted solely from the chemical structures of 16 pyrazolo-diazine and triazine analogs following the prediction of the equilibrium molecular geometry of each analog at the DFT level using B88-LYP functional energy and double zeta valence polarized (DZVP) basis set. It was found that dipole moment, excitation energy, the energy value of LUMO, solvent accessible surface area, and heat of formation were the key molecular descriptors in descriping the cytotoxic effect of those compounds against EAC.

Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1: recent developments concerning substrates and inhibitors of a promising therapeutic target.

SSAO/VAP-1 is not only involved in the metabolism of biogenic and xenobiotic primary amines and in the production of metabolites with cytotoxic effects or certain physiological actions, but also plays a role, for example, as an adhesion molecule, in leukocyte trafficking, in regulating glucose uptake and in adipocyte homeostasis. Interest in the enzyme has been stimulated by the findings that the activities of the SSAOs are altered (mostly increased) in various human disorders, including diabetes, congestive heart failure, liver cirrhosis, Alzheimer's disease and several inflammatory diseases, although the underlying causes are often unknown. On the basis of their insulin-mimicking effect, SSAO substrates are possibly capable of ameliorating metabolic changes in diabetes, while SSAO inhibitors (somewhat of a contradiction) are of potential benefit in preventing diabetes complications, atherosclerosis and oxidative stress contributing to several disorders or modulating inflammation, and hence may be of substantial therapeutic value. Great efforts have been made to develop novel compounds which may lead to future drugs useful in therapy, based on their effects on SSAO/VAP-1, and some of the results relating to novel substrates and inhibitors are surveyed in the present review.

Liposomes as carriers for verbascoside: stability and skin permeation studies.

In this study the influence of liposomal incorporation on both the stability and the in vitro (trans) dermal delivery of verbascoside was evaluated. The effect of drug entrapment into vesicles on its radical scavenging activity was also studied. Liposomes were obtained from soy phosphatidylcholine and cholesterol according to the film hydration method. Stability of verbascoside-loaded vesicles was studied over 6 months. Results showed that verbascoside can be incorporated in liposomes (E% = 57-66%), preventing its degradation. Stability studies (dynamic lager light scattering [DLLS] measurements and transmission electron microscopy [TEM] visualization) pointed out that vesicles were stable for 90 days and neither verbascoside leakage nor vesicle size alteration occurred during this period. The effects of vesicular incorporation on verbascoside diffusion through skin were investigated in vitro using newborn pig skin. Results showed that liposomes promoted drug accumulation into the stratum corneum but they did not give rise to any significant transdermal verbascoside delivery. Finally, results obtained from a 1, 1-diphenyl-2-pierylhydrazyl (DPPH) radical assay demonstrated that liposomes did not interfere with the radical scavenging activity of verbascoside.

Differences in Epidural Pathology between Cervical and Thoracolumbar Intervertebral Disk Extrusions in Dogs.

BACKGROUND: Although the basic pathophysiology is the same in both cervical and thoracolumbar intervertebral disk (IVD) extrusions, there are considerable clinical differences that have only been partially explained. HYPOTHESIS/OBJECTIVES: The epidural inflammatory response differs between cervical and thoracolumbar IVD extrusions. ANIMALS: Fifty-five dogs with cervical and 80 dogs with thoracolumbar IVD extrusions. METHODS: Clinical data and histopathologic variables were investigated. Associations between severity of epidural inflammation and clinical and pathologic variables, impact of chondrodystrophic phenotype, and localization (cervical versus thoracolumbar) were evaluated statistically. RESULTS: Dogs with cervical IVD extrusion were significantly older (P < 0.001), had less severe and longer duration of neurologic signs (both P < 0.001), were more painful (P = 0.038), and had a better outcome (P = 0.005) than dogs with a thoracolumbar IVD extrusion. On histopathology, cervical epidural material had less severe calcification (P = 0.002) and inflammation (P < 0.001). No significant differences regarding chondrodystrophic phenotype were found. CONCLUSION AND CLINICAL IMPORTANCE: There was significantly less intensive inflammatory response in the cervical epidural space. This observation correlated positively with less nucleus pulposus calcification in cervical extrusions indicating biochemical, metabolic, and biomechanical differences between the 2 locations, which remain to be characterized in future studies.

Novel drug delivery systems for natural extracts: The case study of Vitis Vinifera extract-SiO2 nanocomposites.

Ball Milling technique has been used to prepare for the first time Vitis Vinifera extract-silica nanocomposites (VV-SiO2 NCs), which combine the pharmacological effects of the extract with the effectiveness of silica as drug delivery system and active component in the treatment of wound healing. Different contents (1.0, 9.0 and 33.0 wt%) of Vitis Vinifera ethanolic extract were loaded into the silica matrix by grinding the extract with fumed silica using a planetary mill apparatus. The effect of the starting mixture composition and milling time on the final products was examined. The efficiency of the milling process was studied by X-ray Powder Diffraction, Nuclear Magnetic Resonance, and Infrared Spectroscopy, indicating that the natural extract was not affected by the increasing of the milling time. The successful loading of the extract was demonstrated by Nitrogen adsorption/desorption measurements, which showed a decrease in the SSA and pore volume of the silica with the increasing of the extract amount. Morphology of the nanocomposites, investigated by Scanning Electron Microscopy, showed an increased agglomeration in the nanocomposites with the increment of the VV extract amount. Studies on the total phenol quantification and antioxidant activity of the natural extract before and after incorporation in the silica matrix were also carried out. The obtained results indicate that the milling process does not alter the VV extract components, which result to be embedded in the silica matrix. An increase of the antioxidant activity with the increment of the extract amount in the nanocomposites, up to values comparable to the pure VV extract, was also observed.

Primary Postnatal Dorsal Root Ganglion Culture from Conventionally Slaughtered Calves.

Neurological disorders in ruminants have an important impact on veterinary health, but very few host-specific in vitro models have been established to study diseases affecting the nervous system. Here we describe a primary neuronal dorsal root ganglia (DRG) culture derived from calves after being conventionally slaughtered for food consumption. The study focuses on the in vitro characterization of bovine DRG cell populations by immunofluorescence analysis. The effects of various growth factors on neuron viability, neurite outgrowth and arborisation were evaluated by morphological analysis. Bovine DRG neurons are able to survive for more than 4 weeks in culture. GF supplementation is not required for neuronal survival and neurite outgrowth. However, exogenously added growth factors promote neurite outgrowth. DRG cultures from regularly slaughtered calves represent a promising and sustainable host specific model for the investigation of pain and neurological diseases in bovines.

Development of curcumin loaded sodium hyaluronate immobilized vesicles (hyalurosomes) and their potential on skin inflammation and wound restoring.

In the present work new highly biocompatible nanovesicles were developed using polyanion sodium hyaluronate to form polymer immobilized vesicles, so called hyalurosomes. Curcumin, at high concentration was loaded into hyalurosomes and physico-chemical properties and in vitro/in vivo performances of the formulations were compared to those of liposomes having the same lipid and drug content. Vesicles were prepared by direct addition of dispersion containing the polysaccharide sodium hyaluronate and the polyphenol curcumin to a commercial mixture of soy phospholipids, thus avoiding the use of organic solvents. An extensive study was carried out on the physico-chemical features and properties of curcumin-loaded hyalurosomes and liposomes. Cryogenic transmission electron microscopy and small-angle X-ray scattering showed that vesicles were spherical, uni- or oligolamellar and small in size (112-220 nm). The in vitro percutaneous curcumin delivery studies on intact skin showed an improved ability of hyalurosomes to favour a fast drug deposition in the whole skin. Hyalurosomes as well as liposomes were biocompatible, protected in vitro human keratinocytes from oxidative stress damages and promoted tissue remodelling through cellular proliferation and migration. Moreover, in vivo tests underlined a good effectiveness of curcumin-loaded hyalurosomes to counteract 12-O-tetradecanoilphorbol (TPA)-produced inflammation and injuries, diminishing oedema formation, myeloperoxydase activity and providing an extensive skin reepithelization. Thanks to the one-step and environmentally-friendly preparation method, component biocompatibility and safety, good in vitro and in vivo performances, the hyalurosomes appear as promising nanocarriers for cosmetic and pharmaceutical applications.

Microbiological survey of raw and ready-to-eat leafy green vegetables marketed in Italy.

The presence of foodborne pathogens (Salmonella spp., Listeria monocytogenes, Escherichia coli O157:H7, thermotolerant Campylobacter, Yersinia enterocolitica and norovirus) in fresh leafy (FL) and ready-to-eat (RTE) vegetable products, sampled at random on the Italian market, was investigated to evaluate the level of risk to consumers. Nine regional laboratories, representing 18 of the 20 regions of Italy and in which 97.7% of the country's population resides, were involved in this study. All laboratories used the same sampling procedures and analytical methods. The vegetable samples were screened using validated real-time PCR (RT-PCR) methods and standardized reference ISO culturing methods. The results show that 3.7% of 1372 fresh leafy vegetable products and 1.8% of 1160 "fresh-cut" or "ready-to-eat" (RTE) vegetable retailed in supermarkets or farm markets, were contaminated with one or more foodborne pathogens harmful to human health.

Postreceptoral contribution to macular dysfunction in retinitis pigmentosa.

PURPOSE: To understand the sites of macular dysfunction in retinitis pigmentosa by evaluating focal electroretinogram (FERG) fundamental and second harmonic components, which are dominated by the activity of the outer and inner retina, respectively. METHODS: FERGs were recorded in response to a uniform field (9 degrees x 9 degrees) flickered sinusoidally at either 8 Hz or 32 Hz. The fundamental components of the responses to both the 8-Hz and 32-Hz stimuli and the second harmonic of the response to the 8-Hz stimulus were measured in their amplitudes and phases. Normal subjects (n = 17), as well as patients with typical retinitis pigmentosa (n = 22), cone dystrophy (CD, n = 7) and X-linked congenital retinoschisis (XLR, n = 5) served as subjects. The fundamental (32-Hz)-second harmonic (8 Hz) amplitude ratio was taken as an index of the relative function of outer-inner layers of the macula. RESULTS: Compared to controls, patients with retinitis pigmentosa showed losses of both FERG fundamental and second harmonic and an increase of the fundamental-second harmonic ratio. Patients with CD also showed losses of both fundamental and second harmonic, but the fundamental-second harmonic ratio was normal. Patients with XLR had a selective loss of the second harmonic, resulting in an increased fundamental-second harmonic ratio. On average, the fundamental-second harmonic ratio of patients with retinitis pigmentosa tended to increase with age. CONCLUSIONS: The results suggest that in retinitis pigmentosa, both receptoral and postreceptoral sites contribute to macular dysfunction. This differs from CD and XLR, where losses appear more selective for the outer and the inner retina. Postreceptoral losses in retinitis pigmentosa may become larger with increasing age.

Retinal sensitivity to flicker modulation: reduced by early age-related maculopathy.

PURPOSE: To evaluate retinal, cone-mediated flicker sensitivity (CFS) in age-related maculopathy (ARM) by quantifying response gain and threshold of the focal electroretinogram (FERG) to flicker modulation. METHODS: Nineteen patients with ARM (visual acuity > or =20/30) and 11 age-matched control subjects were examined. Twelve patients had less than 20 soft drusen in the macular region and no hyper-/hypopigmentation (early lesion), whereas seven had more than 20 soft drusen and/or focal hyper-/hypopigmentation (advanced lesion). Macular (18 degree ) FERGs were elicited by a sinusoidally flickering (41 Hz) uniform field (on a light-adapting background) whose modulation depth was varied between 16.5% and 94%. Amplitude and phase of the response's fundamental harmonic were measured. RESULTS: In both control subjects and patients with ARM, log FERG amplitude increased with log stimulus modulation depth with a straight line (power law) relation. However, the slope (or gain) of the function was, on average, steeper in control subjects than in patients with either early or advanced lesions. Mean FERG threshold, estimated from the value of the log modulation depth that yielded a criterion response, did not differ between control subjects and patients with early lesions but was increased (0.35 log units) compared with control subjects in those with advanced lesions. In both patient groups, but not in control subjects, mean FERG phase tended to delay with decreasing stimulus modulation depth. CONCLUSIONS: Retinal CFS losses can be detected in ARM by evaluating the FERG as a function of flicker modulation depth. Reduced response gain and phase delays, with normal thresholds, are associated with early lesions. Increased response thresholds, in addition to gain and phase abnormalities, may reflect more advanced lesions. Evaluating CFS by FERG may directly document different stages of macular dysfunction in ARM.

Microemulsions for topical delivery of 8-methoxsalen.

8-Methoxsalen (8-MOP) and related furocumarins have been extensively used for the treatment of hyperproliferative skin diseases in association with long-wavelength UVA light. In order to develop alternative formulations for the topical administration of 8-MOP, microemulsions were evaluated as delivery vehicles. Six microemulsion formulations were prepared using water, isopropyl myristate (IPM) and Tween((R)) 80: Span((R)) 80: 1,2-Octanediol (3:1:1.2 w/w). The microemulsions were characterized using conductimetric and dynamic light scattering analyses. The ability of the systems to deliver 8-MOP into and through the skin was evaluated in vitro using newborn pig-skin. The in vitro permeation data showed that the novel microemulsions increased the 8-MOP total penetration through the skin by order of 1.9-4.5, as compared with IPM. In general, the accumulation of 8-MOP into the skin was increased by a factor of 1.5-4.5 by the microemulsion systems with respect to their total amount of drug delivered across the skin. These results suggest that the studied microemulsion systems may be appropriate vehicles for the topical delivery of 8-MOP.