Siro Passi

Concomitant alterations in intragastric pH and ascorbic acid concentration in patients with Helicobacter pylori gastritis and associated iron deficiency anaemia

Background: Seroepidemiological and clinical studies suggest that Helicobacter pylori may cause iron deficiency anaemia (IDA) in the absence of peptic lesions by undefined mechanisms, which still remain to be fully elucidated. Gastric acidity and ascorbic acid (AA) promote iron absorption. AA is lowered in the presence of H pylori infection. H pylori can cause atrophic body gastritis with achlorhydria, decreased iron absorption, and consequent IDA. Whether alterations in intragastric acidity and AA concentrations play a role in IDA developing in patients with H pylori gastritis remains to be determined. Aim: To evaluate gastric juice pH and gastric juice and plasma AA in patients with H pylori infection and unexplained IDA, compared with controls with IDA and a healthy stomach or with controls with H pylori infection and no IDA. Results: Patients with IDA and H pylori gastritis were characterised by concomitant increased intragastric pH (median value 7) and decreased intragastric AA (median value 4.4 μg/ml) compared with controls with a healthy stomach (median pH 2; median intragastric AA 17.5 μg/ml) and with H pylori positive controls without IDA (median pH 2.1; median intragastric AA 7.06 μg/ml). Intragastric AA was inversely related to pH (r=−0.40, p=0.0059) and corporal degree of gastritis (r=−0.53, p=0.0039). Plasma AA concentrations were lower in all infected groups than in healthy controls. Conclusions: Patients with unexplained IDA and H pylori gastritis present concomitant changes in intragastric pH and AA that may justify impaired alimentary iron absorption and consequent IDA.

Lipophilic antioxidants in human sebum and aging.

Skin surface lipids (SSL), a very complex mixture of sebum mixed to small amounts of epidermal lipids, mantle the human epidermis, thus representing the outermost protection of the body against exogenous oxidative insults. The present work is a systematic and quantitative analysis of upper-chest SSL and their content in antioxidants in 100 healthy volunteers, divided into five age groups using TLC, HPLC, and GC-MS methods. Further, the effect of exposing SSL in vitro to increasing doses of UV irradiation was examined. Straight monounsaturated and diunsaturated as well as branched monounsaturated fatty acids of triglycerides and pooled fractions were found to be higher at maturity than in childhood and in advancing age. Diunsaturated fatty acids were below 3% of the total and constituted exclusively of C18:2 j 5,8 , C20:2 j 7,10 , C18:2 j 9,12 . Squalene, vitamin E (vit. E) and Coenzyme Q 10 (CoQ 10 ) were found to increase from childhood to maturity to decrease again significantly in old age. Vitamin E and CoQ 10 were the only known lipophilic antioxidants present in SSL. In spite of their low levels they were found to synergically inhibit the UV induced depletion of squalene, cholesterol and of unsaturated fatty acids of SSL. In fact, exposure of SSL to increasing amounts of UV irradiation led preferentially to lowering of the levels of vit. E and CoQ 10 . Four minimal erythema dose (MED) (5.6 J/cm 2 ) were able to deplete 84% vit. E and 70% ubiquinone, and only 13% squalene. Diunsaturated and monounsaturated fatty acids as well as cholesterol were unaffected even following 10 MED UV exposures, which produced a 26% loss of squalene. The same UV dose when applied in the absence of vit. E and CoQ 10 produced a 90% decrease of squalene.

Antimitochondrial effect of saturated medium chain length (C8-C13) dicarboxylic acids

In isolated rat liver mitochondria, respiration was competitively inhibited by medium chain length (C8 to C13) dicarboxylic acids to different extents: the higher the number of carbon atoms up to C12, the greater the inhibition. In particular, experiments on submitochondrial particles showed that the competitive inhibition concerned the following enzymes: NADH dehydrogenase, succinic dehydrogenase and reduced ubiquinone: cytochrome c oxido-reductase. These results tend to confirm the suggestion that the melanocytotoxic effect of dicarboxylic acids, which are also competitive inhibitors of tyrosinase, may be primarily due to an antimitochondrial effect rather than being tyrosinase-dependent.

Blood antioxidant status and urinary levels of catecholamine metabolites in β-thalassemia

It has been reported that iron overload in beta-thalassemia leads to an enhanced generation of reactive oxygen species and to oxidative stress. We have studied the oxidant/antioxidant imbalance in the blood of 48 transfusion-dependent beta-thalassemic patients (TLP) (17 males, 31 females, 11-22 year), under chelation therapy, and in 40 sex and age matched healthy controls (CTR). Plasma and lymphocyte levels of vitamin E (Vit E), ubiquinol (CoQ10H2), ubiquinone (CoQ10), plasma concentrations of vitamin A (Vit A), beta-carotene, lycopene, vitamin C (Vit C), total thiols, fatty acid patterns of phospholipids (PL-FA), and plasma and urinary markers of lipoperoxidation (TBA-RM, conjugated dienes, and azelaic acid (AZA), as well as the urinary levels of catecholamine and serotonin metabolites, were evaluated by gas chromatography-mass spectrometry (GC-MS), HPLC and spectrophotometry. Routine laboratory blood analyses were performed on the same samples; 39/48 TLP were HCV positive. Blood samples were collected just before transfusion, the 24 h urine samples the day before. Our results clearly showed that a severe oxidative stress occurs in the plasma of TLP in comparison with CTR. In fact, the levels of lipophilic antioxidants and ascorbate were severely depleted: CoQ10H2 (-62.5%), total CoQ10 (-35.1%), Vit E (-43.8%), beta-carotene (-31.1%), lycopene (-63.7%), Vit A (-35.9%), Vit C (-23.1%). The impairment of the antioxidant status was associated with elevated plasma levels of by-products of lipoperoxidation and urinary concentrations of catecholamine metabolites and of AZA, indicating a high degree of both neurological stress and lipoperoxidation. A significant positive correlation was found between vitamin E and non-transferrin-bound iron (NTBI) (r = -0.81; p < 0.001), while no correlation was found between antioxidant depletion and ferritin serum levels, average blood consumption, or the presence of clinical complications. The administration of selective antioxidants along with an appropriate diet might represent a promising way of counteracting oxidative damage and its deleterious effects on the progression of the disease.

Beneficial effect of 15% azelaic acid cream on acne vulgaris

Patients treated with azelaic acid (15%) cream for chloasma reported simultaneous improvement of acne lesions within the treated areas. This prompted an open study of its effect in cases of acne without chloasma. One hundred patients with acne vulgaris were treated for 3–9 months by twice‐daily application of the cream with significant improvement in every case.

Role of skin surface lipids in UV-induced epidermal cell changes.

SummaryUltraviolet irradiation is capable of affecting skin surface lipids, especially squalene and cholesterol, both in vitro and in vivo, with generation of active lipoperoxides. The photodecomposition of the skin lipid component was carefully evaluated by capillary gas-chromatography. The effects of UV-induced lipoperoxides on human keratinocytes in culture and on guinea pig ear slices were compared with those of synthetic lipoperoxides, i.e. cumene hydroperoxide and 13-hydroperoxylinoleate. A time- and dose-dependent effect on protein synthesis and mitotic activity was observed. In cell culture low concentrations (0.05–5 Μg/ml) of peroxidated squalene and synthetic lipoperoxides stimulated the incorporation of radiolabelled thymidine and phenylalanine, while higher concentrations (>10 Μg/ml), or longer periods of treatment, induced cellular damage. In guinea pig ear slices, the lipoperoxides (5–50 Μg/ml) increased aminoacid incorporation and the number of epidermal pigment cells; higher concentrations (>100 Μg/ml) caused a derangement of epidermal structure. The results suggest that UV irradiation of skin generates lipoperoxides from the surface lipids which, in vitro, are capable of producing a number of changes in epidermal cells.

Mechanism of antitumoral activity of catechols in culture

Cell lines Raji and K 562, lacking tyrosinase, and two melanotic human melanoma cell lines (IRE 1 and IRE 2), were exposed to concentrations from 5 X 10(-3) M to 10(-5) M of different phenols which are substrates of tyrosinase, i.e. l-dopa, dopamine, hydroquinone, terbutylcatechol, and of phenols which are not substrates of the tyrosinase, i.e. resorcinol, butylated hydroxyanisole and hydroquinone dimethyl ether. Cultures were carried out in the presence or in the absence of oxygen radical scavenger enzymes superoxide dismutase, catalase and peroxidase. The stability of each substance in culture medium was assayed by high performance liquid chromatography (HPLC). Results showed that: catechols which are substrates of tyrosinase decompose fully after 24 hr in medium; they are equally toxic for melanoma and non-melanoma cell lines; their toxicity increases when they are preincubated in medium for 24 hr and 48 hr before addition of cells; their toxicity is significantly reduced by addition of scavenger enzymes; on the contrary, phenols not substrates of tyrosinase are stable in medium and their toxicity is not reduced by scavenger enzymes. It is concluded that tyrosinase does not play a major role in catechol toxicity in vitro, which is probably due to some products of catechol decomposition, especially oxygen radicals, acting outside the cells.

Saturated dicarboxylic acids as products of unsaturated fatty acid oxidation.

Upon chemical, radiation-induced or enzymatic oxidation, cis-polyunsaturated fatty acids, i.e., C18:2(n-6), C18:3(n-3), C20:2(n-6), C20:3(n-6), C20:3(n-3), C20:4(n-6), C20:5(n-3), C22:2(n-3), C22:4(n-6), C22:6(n-3), were found to generate saturated short and medium-chain length dicarboxylic acids, which can be regarded as a distinctive feature of the particular double bonds positions in the polyunsaturated fatty acid molecule. Two different dicarboxylic acids, which were unambiguously quantified by GC-MS, were produced from a single fatty acid: one deriving from the oxidative splitting at the level of the first double bond in the molecule, the other being two-carbon-atoms lower homologous. Formation of dicarboxylic acids occurred also from triacylglycerols and phospholipids containing cis-polyunsaturated fatty acids. In this case, following oxidation, the diacids remained covalently bound to the starting molecule and transesterification was necessary for identification. Being extremely stable and easily detectable compounds, dicarboxylic acids may be considered potential markers of oxidative attack to both free and esterified unsaturated fatty acids.

Blood levels of vitamin E, polyunsaturated fatty acids of phospholipids, lipoperoxides and glutathione peroxidase in patients affected with seborrheic dermatitis.

Plasma levels of vitamin E (Vit E) and polyunsaturated fatty acids of phospholipids (PUFA-PL) as well as erythrocyte glutathione peroxidase (GSH-Px) activity are significantly lower (P less than 0.001) in patients with seborrheic dermatitis (SD). both HIV seropositive or HIV sero-negative, than in control subjects. No differences are found between HIV sero-positive and sero-negative individuals with SD. The deficiency of PUFA-PL (mainly C20: 3 n-6, C20: 4 n-6 and C22: 6 n-3) which is accompanied by a significant increase of saturated palmitic and stearic acids (P less than 0.001), does not appear to be associated with an active lipoperoxidative process in the plasma. The significant blood deficiency of Vit E, GSH-Px, and particularly of PUFA-PL, may play a pathogenetic role in seborrheic dermatitis.

Simultaneous determination of sorbic acid, benzoic acid and parabens in foods: A new gas chromatography‐mass spectrometry technique adopted in a survey on Italian foods and beverages

A gas chromatographic-mass spectrometric technique is described for the simultaneous determination of sorbates, benzoates and other lipophilic preservatives in foods and beverages. The selected ions monitoring (SIM) technique allowed unambiguous identification of the compounds under study. This methodology eliminated all kinds of interferences from the complex food matrices which affect most routinely-used techniques, HPLC included. A very simple and time-saving extraction procedure was therefore employed, since subsequent purification steps were unnecessary, even for detection of trace levels of preservatives. The detection limits fell within the range of 100-200 pg. With this analytical technique, we have conducted a survey on sorbic acid, benzoic acid, methyl, ethyl, and propyl 4-hydroxybenzoate levels in 249 samples of foods and beverages on sale in markets in the Rome area. Samples were chosen from among those currently preserved by these additives. All compounds were also determined by a routinely-used HPLC technique for method comparison.