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Biomedical subjects

R D'Anna

Publications and source records attributed to R D'Anna.

At least 37 records · Page 2Linked to original sources

HPV-16 E7 but not E6 oncogenic protein triggers both cellular immunosuppression and angiogenic processes.

HPV-16 E6 and E7 oncoproteins impair the cell cycle in human uterine cervix carcinoma cells (HUCC) by acting on p53 and retinoblastoma proteins, respectively. We recently reported that E7 related into the extracellular compartment by HUCC SiHa cells could inhibit immune T-cell response to recall and alloantigens by a mechanism involving an overproduction of the immunosuppressive IFN alpha by antigen presenting cells (APCs). In this study, we found that besides E7, E6 protein and the vascular endothelium growth factor (VEGF) were released into the SiHa cell supernatants, and we further showed that extracellular E7 but not E6 oncoprotein 1) inhibits the immune cell response to recall and alloantigens, and 2) enhances the release of angiogenic cytokines, including TNF alpha, IL-1 beta and IL-6 by macrophages and/or dendritic cells. VEGF unexpectedly released by cancer cells could also contribute to angiogenesis. Thus in HUCC the same E7 oncoprotein which contributes to controlling the cancer cell cycle has the means in its extracellular configuration to contribute to microenvironmental immunosuppressive and angiogenic processes. Neutralizing anti-E7 antibodies either passively administered or induced by active immunization could represent a new immunotherapeutic endeavour to combat the immunosuppression and/or neoangiogenesis effects of extracellular E7 protein.

Cytokines↗

Lack of endogenous estrogens effects on circulating adhesion molecule ICAM-1.

The serum vascular adhesion molecule ICAM-1 that is involved in atherogenesis was determined in fertile, postmenopausal and at term pregnant women. The aim of the study was to ascertain if the antiatherogenic estrogens action may involve this adhesion molecule. The serum ICAM-1 concentrations resulted similar in the three groups studied: 331 +/- 35 ng/ml, 333 +/- 28 ng/ml and 302 +/- 53 ng/ml in fertile, postmenopausal and pregnant subjects respectively, despite the very different estrogen plasma levels. These data, the first on the ICAM-1 serum levels in women with different natural hormonal milieu, demonstrate that estrogens antiatherogenic action is not involving ICAM-1.

Adult↗

Anticardiolipin antibodies in pre-eclampsia and intrauterine growth retardation.

OBJECTIVE: To establish an association of anticardiolipin antibody (ACA) levels and pre-eclampsia or intrauterine growth retardation (IUGR). METHODS: Twenty-eight patients with pre-eclampsia, 28 with IUGR and 28 normotensive control group were matched for maternal age, race, weight, cigarette smoking, and parity. All had plasma anticardiolipin antibodies (GPL and MPL) detected by the modified enzyme-linked immuno-absorbent assay (ELISA) technique. RESULTS: No statistical significant difference in ACA values, both GPL and MPL, was found among the three groups studied Furthermore, none reached a value of ACA that could be considered clinically relevant (> 15). CONCLUSION: No association was found in anticardiolipin antibody levels between pre-eclamptic and IUGR versus the control group.

Adult↗

Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants.

Because of continuous blood transfusions, thalassemia patients are subjected to peroxidative tissue injury by the secondary iron overload. In accordance, analysis of serum from 42 beta-thalassemia patients, aged 4 to 40 years, showed that the mean concentrations of conjugated diene lipid hydroperoxides (CD), lipoperoxides evaluated as malondialdehyde/ thiobarbituric acid (MDA/TBA) adducts, and protein carbonyls increased about twofold with respect to control. Ferritin levels were positively correlated with the amount of MDA (r = .41; P = .007) and showed a positive trend with CD (r = .31; P = .07) and protein carbonyls (r = .35; P = .054), as further evidence of the deleterious effects of high tissue iron levels. Marked changes in the antioxidant pattern were also observed in all patients. Evidence is presented of a net drop in the concentration of ascorbate (-44%), vitamin E (-42%), vitamin A(-44%), beta-carotene (-29%), and lycopene (-67%). On the other hand, an increase of uric acid and bilirubin was observed, whereas serum albumin and glutathione were in the normal range in all patients. As a result, the total serum antioxidant potential, measured as trolox equivalent antioxidant capacity appeared significantly decreased by 14%. Serum levels of vitamin E were inversely correlated with ferritin (r = -.45; P = .003), suggesting a major consumption of this antioxidant under iron overload. Nontransferrin bound iron (NTBI) was in the range 4.5 to 54.8 micrograms/dL (mean, 21.8 +/- 13.9). Although NTBI had a positive trend with ferritin (r = .37, P = .03), no clear correlation was found with either MDA or vitamin E. A mild to severe hepatic damage, as assessed by serum transaminases, was shown in 24 of 42 patients. Serum levels of vitamin E (r = -.49, P = .015), vitamin A (r = -.48, P = .016) and lycopene (r = -.47, P = .020), were inversely correlated with the levels of transminases. On the other hand, lipid-soluble antioxidants in thalassemia patients were depleted to the same extent in hepatitis C virus (HCV)-infected (31 subjects) and in HCV-uninfected (10 subjects), while in the normal range in serum from 30 nonthalassemic patients with HCV-related chronic hepatitis. These results point out that the iron-induced liver damage in thalassemia may play a major role in the depletion of lipid-soluble antioxidants. The variations of the parameters evaluated in the present study were not correlated with the age of the patients. Our results suggest that the measurement of peroxidation products, matched with evaluation of antioxidants, may be a simple measure of iron toxicity in thalessemia, in addition to the conventional indices of iron status.

Adolescent↗

Synergistic interactions between vitamin A and vitamin E against lipid peroxidation in phosphatidylcholine liposomes.

Interactions between alpha-tocopherol and all-trans retinol in suppressing lipid peroxidation were studied in a unilamellar liposomal system of phosphatidylcholine from either egg or soybean, in which peroxidation was initiated by the water-soluble azo initiator 2,2-azobis(2-amidino-propane)hydrochloride and peroxidation was measured as production of conjugated diene hydroperoxides. While all-trans retinol alone was poorly effective, the combination of all-trans retinol with alpha-tocopherol caused an inhibition period far beyond the sum of the inhibition periods observed with individual antioxidants, providing evidence of synergistic interactions. Furthermore, the inhibition rate calculated in the presence of both all-trans retinol and alpha-tocopherol, Rinh(E+A), was lower than Rinh(E) observed with alpha-tocopherol alone, suggesting that the extension of the inhibition time cannot be ascribed only to the antioxidant activity of alpha-tocopherol. The extent of synergism was linear with a molar ratio all-trans retinol/alpha-tocopherol ranging from 0.1 to 1.0, whereas a drop was observed at a ratio of 2.0. Synergistic antioxidant interactions between all-trans retinol and alpha-tocopherol were also evident when peroxidation was evaluated as production of malondialdehyde. A time course study, in which peroxidation of liposomes and depletion of antioxidants were concomitantly monitored, while showing that most of alpha-tocopherol was consumed to bring about the inhibition period, indicated that autooxidative reactions substantially contributed to the rapid depletion of all-trans retinol, when the antioxidants were allowed to act separately. On the other hand, when alpha-tocopherol and all-trans retinol were combined, the consumption of both antioxidants was significantly delayed, indicating reciprocal protection. Regeneration mechanisms cannot be accounted for by our results. The observed synergism between all-trans retinol and alpha-tocopherol does not appear as the result of specific structural interactions in the lipid bilayer. Combination of all-trans retinol with butylated hydroxytoluene, which reduced markedly all-trans retinol oxidation, resulted in a synergistic antioxidant activity greater than that observed with comparable amounts of alpha-tocopherol. In light of the known antioxidant mechanism of retinoids, the data suggest that by limiting autooxidation of all-trans retinol, alpha-tocopherol strongly promotes its antioxidant effectiveness. The concerted radical scavenging action in turn results in a synergistic protection of the lipid system against peroxidative stress and, ultimately, slows down the alpha-tocopherol consumption.

Drug Synergism↗

[The HELLP syndrome. Notes on its pathogenesis and treatment].

In 1982 Weinstein coined the term HELLP syndrome to describe a special group of pre-eclamptic women who had evidence of hemolysis, elevated liver enzymes and low platelets. The question of whether the HELLP syndrome exists as a distinct entity or is a part of a spectrum of pregnancy complications has long been a source of speculation and debate among obstetricians and internists. A review of the literature indicates that the syndrome occurs in post-partum from 20% to 30% of the cases; maternal mortality from 1% to 4% and perinatal mortality from 5% to 40%. Hypertension and proteinuria are frequently associated with HELLP syndrome, but may also be absent. The syndrome is a group of clinical and pathological manifestations resulting from an insult that leads to intravascular platelet activation (thrombocytopenia) and micro-angiopathic hemolytic anemia (elevated total bilirubin and LDH). Endothelial damage and vasospasm are responsible of hepatic hypoperfusion that results in liver damage, as indicated by a rise in circulating liver enzymes. Since natural evolution of HELLP syndrome is the disseminated intravascular coagulation (CID), the interruption of pregnancy is mandatory and irrespective of the gestational age. This is the reason of an high incidence of cesarean section. Visser and Wallemburg (1995) treated 128 pre-eclamptic patients with HELLP syndrome with volume expansion and pharmacologic vasodilatation under invasive haemodynamic monitoring; they tried to delay delivery with the aim of enhancing fetal maturity. A complete reversal of HELLP occurred in 43% of patients. Further investigations will be necessary to confirm this interesting experience.

Female↗

Efficacy of Bio-Catalyzer alpha.rho no.11 (Bio-Normalizer) supplementation against peroxyl radical-induced oxidative damage in rat organ homogenates.

To better delineate the antioxidant potential of Bio-Catalyzer alpha.rho No.11 (Bio-Normalizer), a natural food supplement recently proposed as an antioxidant agent, we investigated the efficacy of Bio-Normalizer supplementation to protect rat organ homogenates against oxidative damage induced in vitro by peroxyl radicals generated in the hydrophobic or in the hydrophilic phase. Bio-Normalizer supplementation efficiently protected rat kidney homogenates against the accumulation of thiobarbituric reactive substances (TBARS), the formation of protein carbonyl derivatives and the depletion of alpha-tocopherol induced by peroxyl radicals generated from the hydrophobic azo-initiator 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN). It also protected the heart but not the liver or the brain homogenates. Bio-Normalizer supplementation did not have effect in any organ homogenates when peroxyl radicals were generated from the hydrophilic azo-initiator 2,2'-azobis (2-amidinopropane) dihydrochloride) (AAPH). In vitro direct addition of aqueous solutions of Bio-Normalizer to the organ homogenates was ineffective against AMVN or AAPH-induced oxidative damage. Our findings expand previous reports on the antioxidant activity of Bio-Normalizer. They confirm that supplemented Bio-Normalizer protects against peroxyl radical-induced oxidative damage and suggest that its antioxidant action depends on in vivo bioactivation, it is organ specific and it is limited to damage induced by peroxyl radicals generated in the hydrophobic phase.

Animals↗

Anatomo-clinical considerations on the ovarian fibroma.

The Authors analysed from an anatomo-clinical point of view, 17 cases of ovarian fibroma, observed during the period between 1968 and 1992. The incidence of ovarian fibroma in this study was 2.52% and it affected women in different age groups, though with greater frequency those above 50 years. Even the symptomatology was variable and was characterized by pain in the hypogastric quadrant (47.1%); alteration of the menstrual cycle (17.6%); metrorrhagic episodes (17.6%); sterility (5.9%). Due to the fact that the ovarian fibroma can appear at any age, this suggests different surgical approaches according to age, general conditions of the patient and fertility.

Adult↗

Bio-Catalyzer alpha . rho No. 11 (Bio-Normalizer) supplementation: effect on oxidative stress to isolated rat hearts.

Bio-Catalyzer alpha . rho No. 11 (Bio-Normalizer), a natural health food product prepared by yeast fermentation of medicinal plants, has been recently reported to possess antioxidant properties. To better define its antioxidant action, we investigated the effects of orally supplemented Bio-Normalizer on oxidative damage in the rat heart. Hearts were isolated from control or Bio-Normalizer supplemented animals and 1) exposed to ischemia-reperfusion using the Langendorff technique, or 2) homogenized and exposed to peroxyl radicals generated from (2,2'-azobis (2,4'-dimethylvaleronitrile) (AMVN). During reperfusion following 40 minutes of ischemia, leakage of lactate dehydrogenase from hearts isolated from Bio-Normalizer supplemented rats was significantly lower than from hearts of control animals. Furthermore, lower levels of AMVN-induced accumulation of thiobarbituric acid reactive substances and of protein carbonyl derivatives were measured in homogenates prepared from hearts isolated from Bio-Normalizer supplemented rats than in samples from control animals. Our findings confirm an antioxidant action of Bio-Normalizer and show that it protects the heart against ischemia-reperfusion induced damage.

Analysis of Variance↗

[Short-term treatment with leuprolide acetate depot before surgical intervention for uterine leiomyomatosis].

It has been amply demonstrated that uterine leiomyoma possess estrogen receptors. On the basis of this presupposition, it is considered logical to use GnRH-agonists which, by reducing the level of estrogen, also reduce the volume of the leiomyoma, although to a varying extent. The maximum reduction which can be obtained occurs, according to published data, between 3 and 6 months of treatment, attaining mean values of approximately 50%. In the author's experience the treatment period was shortened even further by administering only 2 vials of leuprolide depot each month to women who subsequently underwent hysterectomy. The sample group comprised 30 women with uterine leiomyomatosis, of whom 15 were treated with a GnRH analogue and 15 with placebo. The reduction of uterine volume was evaluated by echography and was found to be 40% in the treated group, whereas non change was detected in the "placebo-group".

Adult↗

[Antihypertensive drugs during pregnancy. Effects on the fetus].

After reviewing the literature on this topic, the paper examines fetal effects during maternal anti-hypertensive treatment, assessing both possible teratogenic results and fetal outcome. All anti-hypertensive agents cross the placental barrier and are present in varying concentrations in the fetal circulation, thus provoking varying effects on the cardiocirculatory apparatus and fetal metabolism. Some agents, such as alpha-metildopa, may be considered reliable, whereas others, like ACE-inhibitors, are still used with considerable caution, an attitude which will only change following extensive clinical trials and through post-natal checks.

Antihypertensive Agents↗

Pregnancy in the obese patient.

The authors considered the course of pregnancy, delivery and puerperium in 70 obese women (pre-pregnancy body mass index greater than 30) and some of the neonatal effects of obesity (weight and morbidity). The results have shown that pregnancy in obese woman presents a certain amount of risk which, however, seem inferior to what it has been believed to be so far. Moreover, the authors underline that in order to further reduce this risk it is necessary for the obese patient to be carefully counselled before pregnancy and controlled during the gestation.

Adolescent↗

The residual ovary after hysterectomy.

Of 118 cases of patient who had undergone abdominal hysterectomy with the preservation of one or both the ovaries, only 73 patients (62%) attended for review. Eleven had had cysts of the residual ovary. The occurrence of an asymptomatic pathology in three cases suggest that patients, for whom preservation of an ovary was considered preferable, should undergo a periodic clinical and ultrasonographic review.

Adult↗

[Beta-mimetic tocolysis: maternal and fetal side-effects].

The literature on materno-foetal effects of the administration of beta-mimetic tocolytics has been examined. Data and series observed show a certain number of unwanted maternal and foetal effects of a metabolic and cardiocirculatory nature. Although these are usually reversible, they may, in conditions of latent pathology, turn into serious accidents. Critical evaluation of research carried out makes it possible to reiterate the usefulness of these drugs, always providing that the absolute need to use them can be demonstrated, and that their use is preceded by careful evaluation of the patient's cardiocirculatory and metabolic condition.

Female↗