Light Dosimetry for Intraperitoneal Photodynamic Therapy in a Murine Xenograft Model of Human Epithelial Ovarian Carcinoma

Few studies have been published to date measuring spatially resolved fluence rates in complex tissue geometries. Here the light distributions of three different intraperitoneal light delivery geometries in a murine ovarian cancer model were investigated to assess their influence on the tumorcidal efficacy of photodynamic therapy (PDT). In vivo fluence rate measurements in the peritoneal cavities of mice, with the light intensity being mapped in three transverse planes, were performed using fiber-optic detectors. Three different source fiber designs and placements were tested for their ability to provide uniform irradiation of the peritoneal cavity. The biological response to a PDT protocol comprising three separate treatments administered at 72 h intervals, each consisting of a 0.25 mg kg intraperitoneal injection of benzopor-phyrin derivative-mono acid ring A followed 90 min later by delivery of 15 J of 690 nm light, was measured. The tissue response was evaluated by measuring the number of remaining visible lesions and the total residual tumor mass. Fluence rate measurements showed large variations in the fluence rate distribution for similar intended treatments. The most uniform and reproducible illumination was achieved using two 18 mm long cylindrical emitting optical fibers. The biological response was comparable to that produced when a flat-cleaved end optical fiber is used to illuminate the four quadrants of the abdomen sequentially. While a good reproducibility in tumor induction in this animal model exists, no correlation was found between the fluence rate distribution measured in one group of animals and the biological response in a separate group of similarly treated animals. Due to the large intra-animal variability in fluence rate distribution, representative fluence rate mapping in complex tissue geometries is of limited value when applied to an individual PDT treatment. Thus, surveillance of the fluence rate during individual treatments will be required for acceptable PDT dosimetry. To improve the versatility of this particular animal model for PDT research, a large number of extended sources are required to increase uniformity of the illumination in order to reduce unwanted cytotoxic side effects resulting from foci of high fluence rates. In this way, subsequent increase of the total energy delivered to the tumor may be possible.     

Soot deep oxidation catalyzed by molybdena and molybdates: a thermogravimetric investigation

Molybdena (MoO₃) and molybdates of bismuth (Bi₂Mo₃O₁₂), chromium (Cr₂Mo₃O₁₂), barium (BaMoO₄), manganese (MnMoO₄) and copper (Cu₃Mo₂O₉) were synthesized and characterized by X-ray powder diffractometry and infrared spectroscopy. They were then assessed as ‘loose contact' catalysts for soot deep oxidation (combustion) in air by thermogravimetry. A similar assessment was carried out on commercial chromia (Cr₂O₃) and tungsta (WO₃). Observed high oxidation activity of MoO₃, as compared to both Cr₂O₃ and WO₃, is attributed to the higher volatility (mobility) of MoO_x species. On similar grounds, observed high activity of MoO₃ and Cu₃Mo₂O₉, as compared to the other test molybdates, is explained. Relatively speaking, however, a higher activity was observed for Cu₃Mo₂O₉ than MoO₃, whereby soot ignition temperature decreased from 571°C (uncatalyzed oxidation) to 430°C, to occur within the temperature range of diesel exhaust (200–450°C). This observation is ascribed to copper-promoted redox conduct of Mo(VI) in the oxidation reaction of soot. Kinetics of the reaction was studied non-isothermally, and the kinetic parameters (A, k, ΔE and the reaction order) were calculated.     

Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes paragraph sign

Excessive exposure of solar ultraviolet (UV) radiation, particularly its UV-B component, to humans causes many adverse effects that include erythema, hyperplasia, hyperpigmentation, immunosuppression, photoaging and skin cancer. In recent years, there is increasing use of botanical agents in skin care products. Pomegranate derived from the tree Punica granatum contains anthocyanins (such as delphinidin, cyanidin and pelargonidin) and hydrolyzable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose) and possesses strong antioxidant and anti-inflammatory properties. Recently, we have shown that pomegranate fruit extract (PFE) possesses antitumor promoting effects in a mouse model of chemical carcinogenesis. To begin to establish the effect of PFE for humans in this study, we determined its effect on UV-B-induced adverse effects in normal human epidermal keratinocytes (NHEK). We first assessed the effect of PFE on UV-B-mediated phosphorylation of mitogen-activated protein kinases (MAPK) pathway in NHEK. Immunoblot analysis demonstrated that the treatment of NHEK with PFE (10-40 microg/mL) for 24 h before UV-B (40 mJ/cm(2)) exposure dose dependently inhibited UV-B-mediated phosphorylation of ERKl/2, JNK1/2 and p38 protein. We also observed that PFE (20 microg/mL) inhibited UV-B-mediated phosphorylation of MAPK in a time-dependent manner. Furthermore, in dose- and time-dependent studies, we evaluated the effect of PFE on UV-B-mediated activation of nuclear factor kappa B (NF-kappaB) pathway. Using Western blot analysis, we found that PFE treatment of NHEK resulted in a dose- and time-dependent inhibition of UV-B-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha. Using immunoblot analysis, enzyme-linked immunosorbent assay and electrophoretic mobility shift assay, we found that PFE treatment to NHEK resulted in a dose- and time-dependent inhibition of UV-B-mediated nuclear translocation and phosphorylation of NF-kappaB/p65 at Ser(536). Taken together, our data shows that PFE protects against the adverse effects of UV-B radiation by inhibiting UV-B-induced modulations of NF-kappaB and MAPK pathways and provides a molecular basis for the photochemopreventive effects of PFE.     

Comment on “Isobaric (vapour + liquid) equilibria for the (1-propanol + 1-butanol) binary mixture at (53.3 and 91.3) kPa”

The (vapor + liquid) equilibrium values reported by Mohsen-Nia and Memarzadeh appear to be flawed. In particular, neither the reported experimental activity coefficients are consistent with the reported composition data nor the reported model parameters can be used to adequately represent their experimental data.     

Acidified,Wet, Silica-Supported Tetrabutylammonium Periodate: A Convenient and Mild Reagent for Conversion of Thioamides to Their Corresponding Amides Under Solvent-Free Conditions

A series of thioamides are transformed to their corresponding oxo analogues in good to excellent yields with acidified, wet, silica-supported tetrabutylammonium periodate under solvent-free conditions.     

Synthesis and solution properties of a pH‐responsive cyclopolymer of zwitterionic ethyl 3‐(N,N‐diallylammonio)propanephosphonate

The zwitterionic monomer, ethyl 3‐(N,N‐diallylammonio)propanephosphonate, was cyclopolymerized in aqueous solutions using t‐butylhydroperoxide or ammonium persulfate as initiators to afford a polyphosphonobetaine (PPB). The protonation of P(?O)OEtO^– and deprotonation of ? NH⁺ groups in PPB by HCl and NaOH, gave the corresponding cationic polyphosphononic acid (CPP) and anionic polyphosphonate (APP). The presence of two pH‐responsive functionalities in APP has led to establish the equilibria: APP ? PPB ? CPP, the position of which very much dictates the viscosity behavior of its aqueous solution. The PPB demonstrated “antipolyelectrolyte” viscosity behavior; however, in contrast to many polycarbo‐ and polysulfo‐betaines, it was found to be soluble in salt‐free water as well as in salt‐added solutions. Basicity constant (K₁) of the amine group in APP, as determined by potentiometric technique, were found to be “apparent,” and as such followed the modified Henderson‐Hasselbalch equation. The study demonstrated a correlation between the basicity constants and viscosity values. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Oral feeding of pomegranate fruit extract inhibits early biomarkers of UVB radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis

Pomegranate from the plant Punica granatum L. possesses strong antioxidant and anti-inflammatory properties. Recently, we have demonstrated that treatment of normal human epidermal keratinocytes with pomegranate fruit extract (PFE) inhibited UVB-mediated activation of nuclear factor kappa B (NF-κB) and mitogen activated protein kinases pathways. Here, we evaluated the effect of PFE on early biomarkers of photocarcinogenesis employing SKH-1 hairless mice. PFE was provided in drinking water (0.2%, wt/vol) to SKH-1 hairless mice for 14 days before a single UVB (180 mJ cm⁻²) irradiation. We found that oral feeding of PFE inhibited UVB-induced: (1) skin edema; (2) hyperplasia; (3) infiltration of leukocytes; (4) lipid peroxidation; (5) hydrogen peroxide generation; (6) ornithine decarboxylase (ODC) activity; and (7) ODC, cyclooxygenase-2 and proliferating cell nuclear antigen protein expression. Oral feeding of PFE enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Importantly, PFE treatment further enhanced UVB-mediated increase in tumor suppressor p53 and cyclin kinase inhibitor p21. Furthermore, oral feeding of PFE inhibited UVB-mediated: (1) nuclear translocation of NF-κB; (2) activation of IKKα; and (3) phosphorylation and degradation of IκBα. Taken together, we provide evidence that oral feeding of PFE to mice affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential.     

Synthesis of 3,5-diaryl-4-chlorophthalates by [4+2] cycloaddition of 1-ethoxy-2-chloro-1,3-bis(trimethylsilyloxy)-1,3-diene with dimethyl acetylenedicarboxylate and subsequent site-selective Suzuki-Miyaura reactions

The [4+2] cycloaddition of 1-ethoxy-2-chloro-1,3-bis(trimethylsilyloxy)-1,3-diene with dimethyl acetylenedicarboxylate (DMAD) afforded dimethyl 4-chloro-3,5-dihydroxyphthalate. Site-selective Suzuki-Miyaura reactions of its bis(triflate) provide a convenient approach to 3,5-diaryl-4-chlorophthalates containing two different aryl groups.