Mitochondrial Oxygen Monitoring During Surgical Repair of Congenital Diaphragmatic Hernia or Esophageal Atresia: A Feasibility Study

Current monitoring techniques in neonates lack sensitivity for hypoxia at cellular level. The recent introduction of the non-invasive Cellular Oxygen METabolism (COMET) monitor enables measuring in vivo mitochondrial oxygen tension (mitoPO2), based on oxygen-dependent quenching of delayed fluorescence of 5-aminolevulinic acid (ALA)-enhanced protoporphyri

The long-term effect of lead on the health of preschool children of the industrial city

The biomonitoring of the lead in milk teeth of preschool children has been carried out; features of their psychophysiological state have been studied. The content of delta-aminolevulinic acid (-ALA) and coproporphyrin (CP) in the urine of the examined children, was also determined. An increased content of lead in the milk teeth, increased activity of delta-aminolevulinic acid and deterioration of the psychophysiological parameters of the examined children were determined in the research

Oil components modulate the skin delivery of 5-aminolevulinic acid and its ester prodrug from oil-in-water and water-in-oil nanoemulsions

The study evaluated the potential of nanoemulsions for the topical delivery of 5-aminolevulinic acid (ALA) and methyl ALA (mALA). The drugs were incorporated in oil-in-water (O/W) and water-in-oil (W/O) formulations obtained by using soybean oil or squalene as the oil phase. The droplet size, zeta potential, and environmental polarity of the nanocarriers were assessed as physicochemical properties. The O/W and W/O emulsions showed diameters of 216–256 and 18–125 nm, which, respectively, were within the range of submicron- and nano-sized dispersions. In vitro diffusion experiments using Franz-type cells and porcine skin were performed. Nude mice were used, and skin fluorescence derived from protoporphyrin IX was documented by confocal laser scanning microscopy (CLSM). The loading of ALA or mALA into the emulsions resulted in slower release across cellulose membranes. The release rate and skin flux of topical drug application were adjusted by changing the type of nanocarrier, the soybean oil O/W systems showing the highest skin permeation. This formulation increased ALA flux via porcine skin to 180 nmol/cm2/h, which was 2.6-fold that of the aqueous control. The CLSM results showed that soybean oil systems promoted mALA permeation to deeper layers of the skin from ∼100 μm to ∼140 μm, which would be beneficial for treating subepidermal and subcutaneous lesions. Drug permeation from W/O systems did not surpass that from the aqueous solution. An in vivo dermal irritation test indicated that the emulsions were safe for topical administration of ALA and mALA

Photodynamic therapy: a treatment tool for hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating inflammatory disease of unknown aetiology. The current standard of care for HS includes antibiotics (oral/topical), retinoids (oral/topical) and intralesional steroids. However, the recurrence of the disease and the unsuccessful of the different treatments stimulate findings of different therapy using light source. Among these, photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) has been proposed by some authors recently. In this study we report the experience of 15 patients affected by HS resistant to conventional therapy treated with ALA-PDT

Isotopic labeling of heme in dehaloperoxidase and CYP102A2 for NMR studies

"13C NMR has been shown to be a powerful tool for probing the electronic distribution in paramagnetic hemes and hemoproteins. Methods that can measure the coordination state and electronic structure of the paramagnetic hemes and hemoproteinscan be very useful for mechanistic strudies. The drawback with this technique is the low natural abundance of 13C in the macrocycle, which hinders sensitivity. Advances in the use of recombinant expression systems have provided us with the resources to selectively label the heme cofactor of paramagnetic heme-containing proteins and enzymes. However, current methodologies of replacing the prosthetic heme with 13C labeled heme in P450 apoproteins are not compatible with cytochromes P450 due to their denaturation upon the removal of the cofactor. We have developed a recombinant expression system, using the hemoprotein dehaloperoxidase as a model, that allows us to selectively label the heme cofactor biosynthetically by supplementing aminolevulinic acid (ALA) deficient E. coli Hu227 cells with synthesized isotopomers of ALA. We have also generated a recombinant plasmid encoding for CYP102A2 that will be compatible with our novel expression system, and have preliminary data indicating this method should be very useful for generating cytochrome P450 samples for 13C analysis."--Abstract from author supplied metadata

Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies

The aim of this work was to test in vitro and in vivo the efficacy of the derivatives of 5-aminolevulinic acid (ALA): hexyl-ALA (He-ALA), undecanoyl-ALA and R,S-2-(hydroximethyl)tetrahydropyranyl-ALA (THP-ALA) as pro-photosensitising agents. The compounds were assayed in a cell line derived from a murine mammary tumour, in tumour explants and after injection of the cells into mice. In vitro, undecanoyl-ALA and THP-ALA did not improve ALA efficacy in terms of porphyrin synthesis. On the other hand, half of the amount of ALA is required to obtain the same plateau amount of photosensitiser from He-ALA. However, this plateau value cannot be surpassed in spite of the four-times higher accumulation of ALA/He-ALA from the ALA derivative. This shows that He-ALA conversion to porphyrins but not He-ALA entry to the cells is limiting. Employing ionic exchange chromatography, we found that 80% of total uptake was He-ALA whereas only 20% was ALA. This suggests that the esterases, probably themselves regulated by the heme pathway, are limiting the conversion of ALA derivatives into porphyrins. A similar situation occurs with THP-ALA. Tumour explant porphyrin results correlate well with cell line data. However, i.p. injection of ALA derivatives to mice resulted in a lower porphyrin concentration in the tumour when compared to the administration of equimolar amounts of ALA, indicating that there should be retention of ALA derivatives either within the blood vessels in the initial phase of distribution and/or within the capillaries of the tumour. © 2004 Cancer Research UK.Fil: Perotti, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Fukuda, Haydee. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Di Venosa, Gabriela Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: MacRobert, A.J.. No especifíca;Fil: Batlle, Alcira María del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Casas, Adriana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentin