Alkylation converts riboflavin into an efficient photosensitizer of phospholipid membranes.

A new decyl chain [-(CH2)9CH3] riboflavin conjugate has been synthesized and investigated. A nucleophilic substitution (SN2) reaction was used for coupling the alkyl chain to riboflavin (Rf), a model natural photosensitizer. As expected, the alkylated compound (decyl-Rf) is significantly more lipophilic than its precursor and efficiently intercalates within phospholipid bilayers, increasing its fluorescence quantum yield. The oxidative damage to lipid membranes photoinduced by decyl-Rf was investigated in large and giant unilamellar vesicles (LUVs and GUVs, respectively) composed of different phospholipids. Using a fluorogenic probe, fast radical formation and singlet oxygen generation was demonstrated upon UVA irradiation in vesicles containing decyl-Rf. Photosensitized formation of conjugated dienes and hydroperoxides, and membrane leakage in LUVs rich in poly-unsaturated fatty acids were also investigated. The overall assessment of the results shows that decyl-Rf is a significantly more efficient photosensitizer of lipids than its unsubstituted precursor and that the association to lipid membranes is key to trigger phospholipid oxidation. Alkylation of hydrophilic photosensitizers as a simple and general synthetic tool to obtain efficient photosensitizers of biomembranes, with potential applications, is discussed.

Singlet Oxygen Flux, Associated Lipid Photooxidation, and Membrane Expansion Dynamics Visualized on Giant Unilamellar Vesicles.

The physical properties of lipid membranes depend on their lipid composition. Photosensitized singlet oxygen (1O2) provides a handle to spatiotemporally control the generation of lipid hydroperoxides via the ene reaction, enabling fundamental studies on membrane dynamics in response to chemical composition changes. Critical to relating the physical properties of the lipid membrane to hydroperoxide formation is the availability of a sensitive reporter to quantify the arrival of 1O2. Here, we show that a fluorogenic α-tocopherol analogue, H4BPMHC, undergoes a >360-fold emission intensity enhancement in liposomes following a reaction with 1O2. Rapid quenching of 1O2 by the probe (kq = 4.9 × 108 M-1 s-1) ensures zero-order kinetics of probe consumption. The remarkable intensity enhancement of H4BPMHC upon 1O2 trapping, its linear temporal behavior, and its protective role in outcompeting membrane damage provide a sensitive and reliable method to quantify the 1O2 flux on lipid membranes. Armed with this probe, fluorescence microscopy studies were devised to enable (i) monitoring the flux of photosensitized 1O2 into giant unilamellar vesicles (GUVs), (ii) establishing the onset of the ene reaction with the double bonds of monounsaturated lipids, and (iii) visualizing the ensuing collective membrane expansion dynamics associated with molecular changes in the lipid structure upon hydroperoxide formation. A correlation was observed between the time for antioxidant H4BPMHC consumption by 1O2 and the onset of membrane fluctuations and surface expansion. Together, our imaging studies with H4BPMHC in GUVs provide a methodology to explore the intimate relationship between photosensitizer activity, chemical insult, membrane morphology, and its collective dynamics.

Synthesis, Characterization and Photocleavage of Bis-decyl Pteroic Acid: A Folate Derivative with Affinity to Biomembranes†.

Here, we provide mechanistic insight to the photocleavage of a compound in the folate family, namely pteroic acid. A bis-decyl chain derivative of pteroic acid was synthesized, structurally characterized and photochemically investigated. We showed that, like folic acid, pteroic acid and the decylated derivative undergo a photocleavage reaction in the presence of H2 O, while no reaction was observed in methanol solution. Furthermore, density functional theory calculations were carried out to predict relative stabilities of hypothetical mono-, bis- and tris-decylated pteroic acid derivatives to help rationalize the regioselectivity of the bis-decyl pteroic acid product. Additionally, the lipophilicity of the bis-decyl pteroic acid appears to confer a hydrophobic property enabling an interaction with biomembranes.

Proximal endovascular blood flow shunt for thoracoabdominal aortic aneurism without total aortic clamping.

The authors present a surgical approach to type III and IV Crawford aneurysms that does not need total aortic clamping, which allows the more objective prevention of direct ischemic damage, as well as its exclusion by the endoprosthesis implantation, shunting the flow to the synthetic graft.

Proximal endovascular blood flow shunt for thoracoabdominal aortic aneurism without total aortic clamping / Desvio de fluxo sanguineo endovascular proximal para derivaçao cirúrgica de aneurisma toracoabdominal sem clampeamento total da aorta

The authors present a surgical approach to type III and IV Crawford aneurysms that does not need total aortic clamping, which allows the more objective prevention of direct ischemic damage, as well as its exclusion by the endoprosthesis implantation, shunting the flow to the synthetic graft.

Os autores apresentam uma abordagem cirúrgica aos aneurismas do tipo III e IV de Crawford em que não é necessário o pinçamento total da aorta, o que permite a prevenção do dano isquêmico direto de forma mais objetiva, assim como sua exclusão por implante de endoprotese desviando o fluxo para o enxerto sintético

Embolização pré operatória de tumores renais com microparticulas esféricas de tecnologia nacional. (Spherus®-First line Brasil) / Pre operative embolization of renal tumors with microspherical particles of national technology (Spherus®-First line Brasil)

Os autores relatam pela primeira vez utilização de uma nova partícula para embolização, constituída de um núcleo de acetato de polivinil revestido por polivinil-álcool, de forma esférica (Spherus®-First Line Brasil), como preparo pré-operatório em três pacientes portadores de neoplasia renal, na intenção de diminuir o tamanho do tumor e prevenir complicações hemorrágicas durante o ato operatório. Estas novas partículas foram projetadas e elaboradas nos laboratórios da COPPE/UFRJ. A embolização intra-arterial pré-operatória com estas novas partículas ocasionou acentuada isquemia em todo o tecido tumoral facilitando o procedimento cirúrgico.

The authors report a brand new component for embolization composed by a polivinil acetate core and a polivinil-alcohol coat in a microspherical form ( Spherus®-First Line Brasil) used as preoperative management in three patients with renal tumors in an attempt to reduce the size of the tumors and to avoid hemorrhagic complications during the operations. This new component was developed in COPPE/UFRJ laboratories. The preoperative arterial embolization with this new component caused strong ischemia in the tumor tissue , facilitating the operative procedure.

Tratamiento del Cáncer inoperable del pulmón mediante interferón alfaleucocitario más radioterapia. resultado en los 10 primeros casos / Treatment for inoperable cancer of the lung using alphaleukocytic interferon combined with radiotherapy: result in the first 10 cases

Desde enero de 1983, comenzamos a tratar los cánceres inoperables del pulmón mediante la combinación de interferón alfaleucocitario más radioterapia. Ocho pacientes tenían carcinomas epidermoides del pulmón y 2, adenocarcinomas. Este tratamiento logró la regresión de los síntomas en todos los pacientes y obtuvo mejoría radiológica en todos; el diámetro mayor del tumor se redujo en una magnitud que osciló entre el 90 y el 40

de este diámetro. No se constataron reacciones de consideración con este tratamiento. De los 10 pacientes 9 estaban vivos en enero de 1986, con 36; 28; 16; 15; 12; 10; 9; y 8 meses de evolución. Estos resultados nos hacen concluir que esta combinación terapéutica tiene su lugar en el tratamiento de esta afección (AU)

Tratamiento del Cáncer inoperable del pulmón mediante interferón alfaleucocitario más radioterapia: resultado en los 10 primeros casos / Treatment for inoperable cancer of the lung using alphaleukocytic interferon combined with radiotherapy: result in the first 10 cases

Desde enero de 1983, comenzamos a tratar los cánceres inoperables del pulmón mediante la combinación de interferón alfaleucocitario más radioterapia. Ocho pacientes tenían carcinomas epidermoides del pulmón y 2, adenocarcinomas. Este tratamiento logró la regresión de los síntomas en todos los pacientes y obtuvo mejoría radiológica en todos; el diámetro mayor del tumor se redujo en una magnitud que osciló entre el 90 y el 40% de este diámetro. No se constataron reacciones de consideración con este tratamiento. De los 10 pacientes 9 estaban vivos en enero de 1986, con 36; 28; 16; 15; 12; 10; 9; y 8 meses de evolución. Estos resultados nos hacen concluir que esta combinación terapéutica tiene su lugar en el tratamiento de esta afección