Hematoporphyrin-based photodynamic therapy for cutaneous squamous cell carcinoma in cats

Photodynamic therapy (PDT) using a haematoporphyrin derivative (Photogem (R), General Physics Institute and clustes Ltda) as photosensitizer and light emitting diodes (LEDs) as the light source was evaluated in 12 cats with cutaneous squamous cell carcinoma. Lesions were illuminated with LEDs, (300 J/cm for 30 min) 24 h after the administration of the photosensitizer. Clinical responses were classified as complete disappearance of the tumour with total re-epithelialization; partial response (a reduction greater than 50%); and no response (less than 50% reduction). Tumours localized to the pinna treated with one (n = 3) or two (n = 4) applications of PDT yielded no response. Highly invasive tumours of the nose and nasal planum also showed no response, after two treatments (n = 2). A combination of PDT and surgery was performed in three cases. Two cats showed partial response and one complete response with one application of therapy 30 days after nasal surgery. Small and noninfiltrative lesions (n = 3) of the nasal planum showed a PR with one application (n = 2) and a CR with two applications (n = 1). This study shows that PDT using Photogem (R) and LEDs can provide local control of low-grade feline squamous cell carcinoma. The addition of PDT to surgery in more invasive cases may help prevent recurrence.

Hematoporphyrin-based photodynamic therapy for cutaneous squamous cell carcinoma in cats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The Applicability Of Ordered Mesoporous Sba-15 And Its Hydrophobic Glutaraldehyde-bridge Derivative To Improve Ibuprofen-loading In Releasing System.

The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.

A New Goniothalamin N-acylated Aza-derivative Strongly Downregulates Mediators Of Signaling Transduction Associated With Pancreatic Cancer Aggressiveness.

In this study, a novel concise series of molecules based on the structure of goniothalamin (1) was synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (Panc-1). Among them, derivative 8 displayed a low IC50 value (2.7 μM) and its concentration for decreasing colony formation was 20-fold lower than goniothalamin (1). Both compounds reduced the levels of the receptor tyrosine kinase (AXL) and cyclin D1 which are known to be overexpressed in pancreatic cancer cells. Importantly, despite the fact that goniothalamin (1) and derivative 8 caused pancreatic cancer cell cycle arrest and cell death, only derivative 8 was able to downregulate pro-survival and proliferation pathways mediated by mitogen activated protein kinase ERK1/2. Another interesting finding was that Panc-1 cells treated with derivative 8 displayed a strong decrease in the transcription factor (c-Myc), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels. Notably, the molecular effects caused by derivative 8 might not be related to ROS generation, since no significant production of ROS was observed in low concentrations of this compound (from 1.5 up to 3 μM). Therefore, the downregulation of important mediators of pancreatic cancer aggressiveness by derivative 8 reveals its great potential for the development of new chemotherapeutic agents for pancreatic cancer treatment.

Enhanced response of the fricke solution doped with hematoporphyrin under X-rays irradiation

The vials filled with Fricke solutions were doped with increasing concentrations of Photogem®, used in photodynamic therapy. These vials were then irradiated with low-energy X-rays with doses ranging from 5 to 20 Gy. The conventional Fricke solution was also irradiated with the same doses. The concentration of ferric ions for the Fricke and doped-Fricke irradiated solutions were measured in a spectrophotometer at 220 to 340 nm. The results showed that there was an enhancement in the response of the doped-Fricke solution, which was proportional to the concentration of the photosensitizer. The use of such procedure for studying the radiosensitizing property of photosensitizers based on the production of free radicals is also discussed.

Higher-derivative supersymmetric gauge theory

We study the one-loop low-energy effective action for the higher-derivative superfield gauge theory coupled to chiral matter.

Potent Cardioprotective Effect of the 4-Anilinoquinazoline Derivative PD153035: Involvement of Mitochondrial K(ATP) Channel Activation

Background: The aim of the present study was to evaluate the protective effects of the 4-anilinoquinazoline derivative PD153035 on cardiac ischemia/reperfusion and mitochondrial function. Methodology/Principal Findings: Perfused rat hearts and cardiac HL-1 cells were used to determine cardioprotective effects of PD153035. Isolated rat heart mitochondria were studied to uncover mechanisms of cardioprotection. Nanomolar doses of PD153035 strongly protect against heart and cardiomyocyte damage induced by ischemia/reperfusion and cyanide/aglycemia. PD153035 did not alter oxidative phosphorylation, nor directly prevent Ca(2+) induced mitochondrial membrane permeability transition. The protective effect of PD153035 on HL-1 cells was also independent of AKT phosphorylation state. Interestingly, PD153035 activated K(+) transport in isolated mitochondria, in a manner prevented by ATP and 5-hydroxydecanoate, inhibitors of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)). 5-Hydroxydecanoate also inhibited the cardioprotective effect of PD153035 in cardiac HL-1 cells, demonstrating that this protection is dependent on mitoK(ATP) activation. Conclusions/Significance: We conclude that PD153035 is a potent cardioprotective compound and acts in a mechanism involving mitoK(ATP) activation.

Enhancement of hematoporphyrin IX potential for photodynamic therapy by entrapment in silica nanospheres

The entrapment of hematoporphyrin IX (Hp IX) in silica by means of a microemulsion resulted in silica spheres of 33 +/- 6 nm. The small size, narrow size distribution and lack of aggregation maintain Hp IX silica nanospheres stable in aqueous solutions for long periods and permit a detailed study of the entrapped drug by different techniques. Hp IX entrapped in the silica matrix is accessed by oxygen and upon irradiation generates singlet oxygen which diffuses very efficiently to the outside solution. The Hp IX entrapped in the silica matrix is also reached by iron(II) ions, which causes quenching of the porphyrin fluorescence emission. The silica matrix also provides extra protection to the photosensitizer against interaction with BSA and ascorbic acid, which are known to cause suppression of singlet oxygen generation by the Hp IX free in solution. Therefore, the incorporation of Hp IX molecules into silica nanospheres increased the potential of the photosensitizer to perform photodynamic therapy.

In Vitro Sun Protection Factor Evaluation of Sunscreens Containing Rutin and its Derivative

This research aimed at determining spectrophotometrically (290 to 320nm) the in vitro Sun Protection Factor (SPF) of sunscreens developed with rutin (R) or succinate rutin (SR), in association or not with UVB filter. Formulations were developed based on phosphate-base O/W emulsions, with (B) or not (A) the presence of polyacrylamide/C13-14 isoparaffin/laureth-7 (PIL), in accordance with the following associations: (a) control; (b) 1.0 % SR; (c) 0.1 % R; (d) 7.5 % ethylhexyl methoxycinnamate (EHMC); (e) 7.5 % EHMC + 0.1 % RS; (0 7.5 % EHMC + 0.1 % R. It was verified a statistical significative elevation of the SPF from 13.93 +/- 0.02 (Af) to 16.63 +/- 0.27 (Bf) and also in relation to 15.53 +/- 0.14 (Bd). According to the results, the EHMC had distinct behavior depending on the presence of bioactive substance and viscosity agent, thus, rutin obtained better profile as a SPF booster in these experimental conditions with the presence of PIL.

New Rapid Derivative Spectrophotometric and Chromatographic Methods for Assay of Loratadine in Tablets and Syrups

New rapid first-derivative spectrophotometric (UVDS) and a stability-indicating high performance liquid chromatographic (HPLC) methods were developed, validated and successfully applied in the analysis of loratadine (LT) in tablets and syrups. In the UVDS method, 0.1 M HCl was used as solvent. The measurements were made at 312.4 nm in the first order derivative spectra. The HPLC method was carried out on a RP-18 column with a mobile phase composed of methanol-water-tetrahydrofuran (50:30:20, v/v/v). UV detection was made at 247 nm. For HPLC methods the total analysis time was <3min, adequate for routine quality control of tablets and syrups containing loratadine.

UV-Derivative Spectrophotometric and Stability-Indicating High-Performance Liquid Chromatographic Methods for Determination of Simvastatin in Tablets

A stability-indicating high-performance liquid chromatographic (HPLC) and a second-order derivative spectrophotometric (UVDS) analytical methods were validated and compared for determination of simvastatin in tablets. The HPLC method was performed with isocratic elution using a C18 column and a mobile phase composed of methanol:acetonitrile:water (60:20:20, v/v/v) at a flow rate of 1.0 ml/min. The detection was made at 239 nm. In UVDS method, methanol and water were used in first dilution and distilled water was used in consecutive dilutions and as background. The second-order derivative signal measurement was taken at 255 nm. Analytical curves showed correlation coefficients > 0.999 for both methods. The quantitation limits (QL) were 2.41 mu g/ml for HPLC and 0.45 mu g/ml for UVDS, respectively. Intra and inter-day relative standard deviations were < 2.0 %. Statistical analysis with t- and F-tests are not exceeding their critical values demonstrating that there is no significant difference between the two methods at 95 % confidence level.

Development and validation of high performance liquid chromatographic and UV-derivative spectrophotometric methods for the determination of sotalol hydrochloride in tablets

High performance liquid chromatographic (HPLC) and UV derivative spectrophotometric (UVDS) methods were developed and validated for the quantitative determination of sotalol hydrochloride in tablets. The HPLC method was performed on a C18 column with fluorescence detection. The excitation and emission wavelengths were 235 and 310nm, respectively. The mobile phase was composed of acetonitrile-water containing 0.1% trietylamine (7:93v/v) and pH adjusted to 4.6 with formic acid. The UVDS method was performed taking a signal at 239.1nm in the first derivative. The correlation coefficients (r) obtained were 0.9998 and 0.9997 for HPLC and UVDS methods, respectively. The proposed methods are simple and adaptable to routine analysis.

A stabilized demethoxyviridin derivative inhibits PI3 kinase

The viridins like demethoxyviridin (Dmv) and wortmannin (Wm) are nanomolar inhibitors of the PI3 kinases, a family of enzymes that play key roles in a host of regulatory processes. Central to the use of these compounds to investigate the role of PI3 kinase in biological systems, or as scaffolds for drug development, are the interrelated issues of stability, chemical reactivity, and bioactivity as inhibitors of PI3 kinase. We found that Dmv was an even more potent inhibitor of PI3 kinase than Wm. However, Dmv was notably less stable than Wm in PBS, with a half-life of 26 min versus Wm`s half-life of 3470 min. Dmv, like Wm, disappeared in culture media with a half-life of less than 1 min. To overcome Dmv`s instability, it was esterified at the C1 position, and then reacted with glycine at the C20 position. The resulting Dmv derivative, termed SA-DmvC20-Gly had a half-life of 218 min in PBS and 64 min in culture media. SA-DmvC20-Gly underwent an exchange reaction at the C20 position with N-acetyl lysine in a manner similar to a WmC20 derivative, WmC20-Proline. SA-DmvC20-Gly inhibited PI3 kinase with an IC(50) of 44 nM, compared to Wm`s IC(50) of 12 nM. These results indicate that the stability of Dmv can be manipulated by reactions at the C1 and C20 positions, while substantially maintaining its ability to inhibit PI3 kinase. Our results indicate it may be possible to obtain stabilized Dmv derivatives for use as PI3 kinase inhibitors in biological systems. (C) 2009 Elsevier Ltd. All rights reserved.

Self-assembled naphthalenediimide derivative films for light-assisted electrochemical reduction of oxygen

This naphthalene diimide derivative, DC18, forms highly conjugated semiconducting stacked assemblies over electrodes after electrochemical conditioning. These molecular materials are very efficient towards electrochemical photoreduction of oxygen under visible light.

Gas-phase dissociation of 1,4-naphthoquinone derivative anions by electrospray ionization tandem mass spectrometry

Gas-phase dissociation pathways of deprotonated 1,4-naphthoquinone (NQ) derivatives have been investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The major decomposition routes have been elucidated on the basis of quantum chemical calculations at the B3LYP/6-31+G(d,p) level. Deprotonation sites have been indicated by analysis of natural charges and gas-phase acidity. NQ anions underwent an interesting reaction under collision-induced dissociation conditions, which resulted in the radical elimination of the lateral chain, in contrast with the even-electron rule. Possible pathways have been suggested, and their mechanisms have been elucidated on the basis of Gibbs energy and enthalpy values for the anions previously described at each pathway. Copyright (C) 2009 John Wiley & Sons, Ltd.