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Notes: We present a new method to evaluate the photo-oxidative activity of sunscreening agents based on the photodynamic oxidation of uric acid. Uric acid was selected as the oxidant probe for its high reactivity to singlet oxygen and oxygen radicals, high sensitivity of detection using electrochemical (EC) techniques, low light absorptivity and high photochemical stability in the UVA/B region of interest, and stability to autoxidation. The method is demonstrated by the photodynamic oxidation of uric acid on co-irradiation with Rose Bengal, a highly efficient photosensitizing dye for the production of singlet oxygen (1O2). Using this assay we found that the relative photodynamic oxidation rates of UVB-absorbing sunscreens in 80% methanol on irradiation with 〉290 nm light decreased in the order 2-ethylhexyl 4-dimethylaminobenzoate (DMABA-2EH) ≫ 2-ethylhexyl 4-methoxycinnamate (MCA-2EH) and the experimental sunscreens, 1-(1,1-dimethylethyl)-3-octanoyl-4,4-dimethyl- 1,4,5,6,-tetrahydropyridine (ICI-319) and 1-(2-methylpropyl)-3-propionyl-4,4-dimethyl-1,4,5,6-tetrahydropyridine (ICI-855). The relative photodynamic oxidation rates of UVA-absorbing sunscreens decreased in the order 4-tert-butyl-4'-methoxydibenzoylmethane (BMDBM) and 4-(2-propyl)benzophenone (PB) 〉 2-hydroxy-4'-methoxy-benzophenone (HMB) and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB). We have confirmed the photodynamic activity of DMABA-2EH for the production of singlet oxygen (1O2) using electron paramagnetic resonance (EPR) spectroscopy and the reagent 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TEMP). We failed to detect the photodynamic production of the oxyradicals, superoxide (O2.-) and hydroxyl radical (HO.) using N-tert-butyl-a-phenylnitrone (PBN) and 5,5-dimethyl-1-pyrrolidine-1-oxide (DMPO) as a result of photochemical interference caused by these spin-trapping reagents. The uric acid photo-oxidation assay was also used to compare the photodynamic reactivity of light-reflective, microfine oxides TiO2, ZnO and ZrO2 suspended in aqueous 80% methanol. All of the microfine oxides (uncoated) showed greater photodynamic reactivity in equimolar dispersion than did any of the organic UVA- and UVB-absorbing sunscreens in homogeneous solution. In this assay the photodynamic oxidation rates for the microfine oxides decreased in the order ZnO ≫ TiO2 (anatase) 〉 ZrO2 〉 TiO2 (rutile). Resume Nous presentons un nouveau procede d'evaluation de l'activite photooxydante d'agents pour ecrans solaires base sur l'oxydation photodynamique de l'acide urique. L'acide urique a ete choisi comme test a l'oxydation en raison de sa forte reactivite a l'oxygene singulet et aux radicaux oxygene, sa haute sensibilite a la detection par les techniques electrochimiques (EC), sa faible capacite d'absorption de la lumiere, sa stabilite photochimique elevee dans le domaine UVA/UVB concerne, et sa stabilite a l'autooxydation. La demonstration du procede est effectuee au travers de l'oxydation photodynamique de l'acide urique co-irradie avec du Rose du Bengale, colorant phosensibilisateur tres efficace pour generer de l'oxygene singulet (1O2). En mettant ce test en oeuvre nous avons trouve que les vitesses relatives d'oxydation photodynamique d'ecrans solaires aux UVB dans due methanol a 80%, irradies avec une lumiere 〉 290nm, diminuent dans l'ordre: 2-ethylhexyl 4-dimethylamino-benzoate (DMABA-2EH) ≫ 2-ethylhexyl 4-methoxycinnamate (MCA-2EH) et les ecrans a l'essai: la 1-(1,1-dimethylethyl)-3-octanoyl-4,4-dimethyl-1,4,5,6-tetrahydopyridine (ICI-319) et la 1-(2-methylpropyl)-3-propionyl-4,4-dimethyl-1,4,5,6-tetrahydropyridine (ICI-855). les vitesses relatives d'oxydation photodynamique d'ecrans solaires aux UVA diminuent dans l'ordre: 4-tert-butyl-4'-methoxydibenzoylmethane (BMDBM) et 4-(2-propyl) benzophenone (PB) 〉 2-hydroxy-4'-methoxybenzophenone (HMB) et 2'2'-dihydroxy-4-methoxybenzophenone (DHMB). Nous avons confirme l'activite photdynamique du DMABA-2EH pour la production d'oxygene singulet (1O2) en utilisant la spectroscopie par resonance paramagnetique electronique et le reactif 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TEMP). Nous n'avons pas pu detecter la production photodynamique des oxyradicaux du superoxyde (O2.) et du radical hydroxyle (HO.) a l'aide de la N-ter-butyl-a- phenylnitrone (PBN) en raison d'interferences photochimiques causees par ces reactifs spin-Bloquants. Le test de photooxydation de l'acide urique a aussi ete utilise pour comparer la reactivite photodynamique d'oxydes microfins reflechisseurs de lumiere TiO2, ZnO et ZrO2 en suspension dans du methanol aqueux a 80%. Tous ces oxydes microfins (non enrobes) ont montre une meilleure reactivite photodynamique en dispersion equimolaire que ne l'a fait aucun des ecrans solaires aux UVA et UVB en solution homogene. Lors de ce test les vitesses d'oxydation photodynamique des oxydes microfins ont diminue dans l'ordre ZnO ≫ TiO2 (anatase) 〉 ZrO2 〉 TiO2 (rutile).

Notes: Alcoholic beverages such as beer and wine are well known to potently stimulate gastric acid secretion, most probably through an increase in circulating gastrin level. The present study examined whether or not wine stimulates gastric acid secretion by a direct effect on parietal cells, enterochromaffin-like (ECL) cells or both.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Gastric mucosa was isolated from female Japanese white rabbits and gland specimens were prepared by the collagenase digestion method. Acid secretion was assessed by gland accumulation of [14C] aminopyrine. The effects of red wine, ethanol, non-alcoholic wine and drugs were determined by incubating gastric glands with aminopyrine. Radioactivity in solubilized glands was determined by a liquid scintillation counting.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Neither wine nor ethanol (diluted 1 : 102 to 1 : 104) had any effect on gastric acid secretion, whereas non-alcoholic wine stimulated acid secretion in a dose-dependent manner. All substances, however, significantly stimulated gastric acid secretion in IBMX (phosphodiesterase inhibitor)-pretreated glands. S-0509 (a CCK-2 receptor antagonist) and atropine had no effect on acid secretion stimulated by wine, ethanol or non-alcoholic wine in IBMX-pretreated glands. Famotidine and omeprazole significantly inhibited the acid secretion resulting from all of the above stimulants. BAPTA (an intracellular Ca2+ chelator) inhibited acid secretion stimulated with wine or ethanol in a dose-dependent manner, but did not inhibit secretion stimulated by non-alcoholic wine.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Wine was found to stimulate gastric acid secretion in gastric glands via two pathways, by an ethanol-induced increase in the concentration of intracellular Ca2+ in parietal cells, and by histamine release from ECL cells potentially induced by constituents present in wine.

Notes: Background:  Interleukin (IL)-10 is a pleiotropic cytokine with a broad spectrum of immunosuppressive and anti-inflammatory effects. IL-10 secretion from alveolar macrophages is defective in patients with asthma and lower concentrations of IL-10 are found in bronchoalveolar lavage (BAL) from asthmatic patients than in normal control subjects. Reduced IL-10 may result in exaggerated and more prolonged inflammatory responses in asthmatic airways. IL-10 acting through the IL-10 receptor (IL-10R) stimulates the transcription factors STAT1 and STAT3.Methods:  We investigated IL-10 and IL-10R expression in normal and asthmatic bronchial epithelium and BAL macrophages using reverse transcription-polymerase chain reaction, immunohistochemistry and Western blotting. The functional effect of IL-10 was examined using granulocyte–macrophage-colony stimulating factor, enzyme-linked immunosorbent assay and Western blotting for phosphorylated STAT1 and STAT3.Results:  IL-10 was not expressed in epithelial cells; furthermore these cells did not express the IL-10R and had no functional response to exogenous IL-10. Bronchial epithelial cells expressed variable levels of phosphorylated STAT1 and STAT3 with no change in expression between normal subjects and asthmatics. IL-10 protein and IL-10R expression was detected in alveolar macrophages from all subjects.Conclusion:  Our study suggests that the bronchial epithelium is not a source of IL-10 and cannot respond to exogenous IL-10 because of a lack of IL-10R expression.

Notes: Tissue localization of collagenous and basement membrane proteins in the extracellular matrix of five sacro-coccygeal chordomas and human fetal notochords was examined immunohistochemically to assess the implications for the histogenesis and histological diagnosis of chordoma. Human fetal notochords and conventional chordomas both exhibited basement membrane proteins (such as type IV collagen and laminin) and type VI collagen on the surfaces of cellular cords. Type II collagen, a main structural protein of cartilage, was also present in both tissues. In the chordomas, however, type II collagen was not so widespread as it was in the notochords, and the predominant collagenous protein was type I. In contrast, an altered deposition of these proteins was noticed in a recurrent tumour which, histologically, showed considerable atypia and eventually metastasized to the liver. The characteristic cartilage-type and basement membrane proteins disappeared and unusual collagen types, such as types III and V, appeared in the stroma. The results further support the notochordal origin of chordoma and suggest that the immunohistochemistry of collagenous and basement membrane proteins may be a helpful criterion for the histological diagnosis and prediction of the biological aggressiveness of chordomas.

Notes: Activated mononuclear cells (lymphocytes and monocytes) (MNCs) circulate in peripheral blood and accumulate in the airways of individuals with steady-state asthma. The expression of adhesion molecules on MNCs of 10 patients with steady-state atopic asthma and 10 non-atopic control subjects was measured by flow cytometry. The mean fluorescence intensity of CD23 (P= 0.0003), CDl la (P= 0.034), and very late antigen-4 (VLA-4) (P= 0.016) was increased on lymphocytes of asthmatic patients relative to those of controls. Although the expression of CD16 (P= 0.002) and CD23 (P= 0.002). which are associated with differentiation into macrophages, was increased on monocytes of patients relative to those of controls, monocyte expression of VLA-4 (P= 0.006) and sialyl Lewis X (P= 0.005) was reduced. The concentration of interleukin-4 (lL-4) in serum was significantly higher in asthmatic patients than in normal subjects (P= 0.023), and a significant correlation was apparent between the serum concentration of lL-4 and the expression of VLA-4 on lymphocytes (p= 0.71, P= 0.03) or on monocytes (p=−0.72, P= 0.03) in asthmatic patients. Results suggest that lL-4 may contribute to the priming of adhesion molecule expression on lymphocytes even in steady-state conditions in individuals with chronic allergic inflammation.