Photodynamic and antiangiogenic activities of parietin liposomes in triple negative breast cancer.

Parietin (PTN) is an anthraquinone with promising efficacy in the inhibition of cancer cell proliferation and tumor growth. Due to its hydrophobicity, PTN is sparingly soluble under physiological conditions and has a low bioavailability. Hence, we presented PTN in liposomes to overcome these drawbacks. The prepared liposomes were characterized and their stability was also assessed in serum. Singlet oxygen quantum yield of PTN loaded liposomes was indirectly quantified using uric acid. The intracellular uptake of liposomes was studied by CLSM which indicated the perinuclear localization of PTN liposomes. Cellular viability assay and live/dead staining demonstrated both light and dose-dependent phototoxicity of PTN on the human breast cancer cell line. The mechanism of cellular uptake was investigated using different pathway inhibitors and the results showed that clathrin-mediated endocytosis is predominant. The colocalization experiment indicated that PTN is localized in both mitochondria and lysosomes. These findings together with flow cytometry analysis elucidated that apoptosis is the main mechanism underlying cell death post-PDT. Finally, the antiangiogenic effect of PTN liposomes was further evaluated in the chorioallantoic membrane (CAM) model and the results indicated that PDT induced vascular response was confined to the irradiated area leaving the non-irradiated unscathed.

Surface tailored zein as a novel delivery system for hypericin: Application in photodynamic therapy.

Zein is an FDA-approved maize protein featured by its manipulative surface and the possibility of fabrication into nanomaterials. Although extensive research has been carried out in zein-based technology, limited work is available for the application of zein in the field of cancer photodynamic therapy (PDT). In this work, we report zein as a carrier for the natural photosensitizer hypericin in the PDT of hepatocellular carcinoma in vitro. Zein was modified through chemical PEGylation to form PEGylated zein micelles that were compared with two zein nanoparticle formulations physically stabilized by either the lecithin/pluronic mixture or sodium caseinate. FT-IR, 1HNMR and HP-SEC MALS approaches were employed to confirm the chemical PEGylation of zein. Our developed zein nanoparticles and micelles were further characterized by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM). The obtained results showed relatively smaller sizes and higher encapsulation of hypericin in the micellar zein than the nanoparticle-based formulations. Phototoxicity on hepatocellular carcinoma (HepG2 cells) manifested a dose-dependent toxicity pattern of all designed zein formulations. However, superior cytotoxicity was prominent for the hypericin-based micelles, which was influenced by the higher cellular uptake profile. Consequently, the treated HepG2 cells manifested a higher level of intracellular generated ROS and disruption of mitochondrial membrane potential, which induced apoptotic cell death. Comparatively, the designed hypericin formulations indicated lower phototoxicity profile in murine fibroblast L929 cells reflecting their safety on normal cells. Our investigations suggested that the surface-modified zein could be employed to enhance the delivery of the hydrophobic hypericin in PDT and pave the way for future in vivo and clinical applications in cancer treatment.

Characterization of ammonia binding to the second coordination shell of the oxygen-evolving complex of photosystem II.

The second-shell ammonia binding sites near the OEC (oxygen-evolving complex) of PSII are characterized by combined Continuum Electrostatic/Monte Carlo (MCCE), QM/MM and DFT calculations and compared with new and earlier experimental measurements. MCCE shows ammonia has significant affinity at 6 positions but only two significantly influence the OEC. Although the pKa of ammonium ion is 9.25, it is calculated to only bind as NH3, in agreement with its low affinity at low pH. The calculations also help explain the experimentally observed competitive binding of ammonia with chloride. Ammonia and Cl- compete for one site. Electrostatic interactions cause Cl- to effect ammonia at two other sites. Cl- stabilizes the multiline g = 2.0 form of the S2 state (OEC Mn oxidation state 3444) while ammonia only binds in the g = 4.1 form of the S2 state (oxidation state 4443) due to the movement of the positive charge between Mn1 and Mn4. One ammonia binds near Mn4 and shares a proton with D2-K317, making the ion pair NH4+K3170D61-, making ammonia binding sensitive to the K317A mutation. The affinity of ammonia is also dependent on the protonation state of water 2, a primary ligand to Mn4.

Comparative outcome of bidirectional Glenn shunt in patients with pulmonary vascular resistance > or = 3.5 woods units versus < 3.5 woods units.

Moderate to severe pulmonary hypertension is considered to be an absolute contraindication to the performance of bidirectional Glenn (BDG) shunting. However, BDG shunting has been performed in young children with pulmonary hypertension associated with unrestricted pulmonary blood flow. In this study, the medical records of patients who underwent BDG starting from October 2000 to March 2004 were reviewed. Patients were divided into 2 groups on the basis of indexed pulmonary vascular resistance (PVRI) measured in room air: a high-risk group (n = 12) with PVRI > or = 3.5 Woods units (WU)/m(2) and a low-risk group (n = 28) with PVRI <3.5 WU/m(2) in room air. The 2 groups were comparable with respect to age, weight, ventricular morphology, pulmonary arterial anatomy, and atrioventricular valve function. Mean pulmonary arterial pressure and PVRI were significantly higher in the high-risk group compared with the low-risk group (39.2 +/- 20.7 vs 15.1 +/- 6.25 mm Hg, p <0.002, and 6.0 +/- 2.5 vs 1.6 +/- 0.82 WU/m(2), p <0.0005, respectively). The ratio of pulmonary flow to systemic flow was 1.45 +/- 0.76 in the high-risk group and 1.24 +/- 1.2 in the low-risk group. In the high-risk group, mean PVRI decreased to 2.0 +/- 1.0 WU/m(2) on 100% oxygen (p <0.0005). A contraindication to Glenn shunting was PVRI >3.5 WU/m(2) on 100% oxygen. Hospital mortality was 17% (2 of 12) in the high-risk group and 4% (1 of 28) in the low-risk group. Of 10 survivors in the high-risk group, 1 had undergone a Kawashima procedure, 7 had undergone Fontan procedures (with 1 death), and 2 were awaiting the completion of Fontan procedures as of this writing. In conclusion, these preliminary data suggest that in young children with increased pulmonary flow, BDG shunting can be safely performed, despite the apparent elevation of pulmonary arterial pressure to inoperable levels, provided PVRI decreases to < or = 3.5 WU/m(2) on 100% oxygen.

Retrograde approach for device closure of muscular ventricular septal defects in children and adolescents, using the Amplatzer muscular ventricular septal defect occluder.

This study presents technique and initial experience of retrograde deployment of the Amplatzer muscular ventricular septal defect occluder (AmVSDo) for closure of muscular ventricular septal defects (VSDs). The conventional technique for closing muscular VSDs involves the creation of an arteriovenous guidewire circuit and use of a transvenous approach for device deployment. Seven patients aged 2.2-15 years underwent transcatheter closure of a muscular VSD using the retrograde approach without making the arteriovenous wire circuit. Mean fluoroscopy and procedural times were compared to those previously reported in publications describing the use of the antegrade approach. Unpaired Student's t-test was used to compare the two parameters in two groups. Our technique was successful in all patients reported. The mean fluoroscopy time in the retrograde versus the antegrade group was 33.8 +/- 20.9 and 41.9 +/- 6.2 minutes, respectively (not significant), and the mean procedural time in the two groups was 91.1 +/- 22.1 and 114 +/- 33.9 minutes respectively (p = 0.025). No complications were noted. We suggest that some muscular VSDs can be safely closed retrogradely without the use of an arteriovenous loop, thus reducing the radiation exposure and also the cost of the procedure. Further studies are needed to confirm this initial experience.

Stent implantation to maintain patency of a stenosed Blalock Taussig shunt.

A 14-year-old female with complex congenital heart disease underwent a left-sided classical Blalock Taussig (BT) shunt 15 days after birth. Ten years after the operation her oxygen saturation had decreased significantly. An angiography revealed a severely stenosed BT shunt. Balloon dilation including implantation of a 6 x 13 mm stent was performed successfully. Immediately after intervention, oxygen saturation rose from 55% to 80 84% in room air. Follow-up at a year and a half later showed the classical BT shunt was still patent.

Successful percutaneous coil occlusion of a large pulmonary arteriovenous malformation.

Pulmonary arteriovenous malformation is one of the rarest congenital anomalies of cardiovascular system. We present a case of 30-year-old female with a large pulmonary arteriovenous malformation (PAVM) arising from the right lower pulmonary artery and draining to the left atrium. She underwent successful embolization using three detachable Cook coils.