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B Bonet

Publications and source records attributed to B Bonet.

At least 19 recordsLinked to original sources
PubMed2006

Long-term reversal of hypocholesterolaemia in patients with chronic hepatitis C is related to sustained viral response and viral genotype.

BACKGROUND: Genotype-3 of hepatitis C virus (HCV) has been associated with serum lipid changes (reversible with sustained viral response) and liver steatosis. AIM: To characterize the relationships among hepatic steatosis, cholesterol and sustained viral response in these patients. METHODS: Patients (n = 215) with chronic hepatitis C (157 with genotype-1 of HCV) had age, body mass index, gender, alcohol intake, glycaemia, serum lipids, transaminases, grade and stage (METAVIR and Scheuer), degree of liver steatosis, sustained viral response, insulinaemia, leptinaemia, beta-hydroxybutyrate and glycerol measured, and were compared with 32 hepatitis B virus (HBV)-infected subjects. RESULTS: Genotype-3 of HCV patients had age-adjusted hypocholesterolaemia and more frequent hepatic steatosis (P < 0.001). Steatosis was inversely correlated with serum cholesterol (P < 0.01) and directly with viral load (P < 0.03). In patients with genotype-3 of HCV and sustained viral response, serum cholesterol increased from 138 (95% CI: 120-151) to 180 mg/dL (95% CI: 171-199) 12 months after treatment conclusion (P < 0.0001). By contrast, cholesterol values were unchanged in genotype-3 of HCV non-responders and in patients with genotype-1 of HCV regardless of response. Rising cholesterol in sustained viral response did not parallel the changes in beta-hydroxybutyrate. CONCLUSIONS: Besides causing hepatic steatosis, genotype-3 specifically decreases serum cholesterol. This interference with the metabolic lipid pathway is related to viral load, is reversed with sustained viral response, and seems unrelated to mitochondrial dysfunction.

C-Peptide↗
PubMed2006

[Minimal invasive surgical of intersex abnormalities: our experience].

The term intersex makes reference to either newborn infants who show ambiguous external genitals or those who, having a normal phenotype, show growth alterations in the puberty. The etiologic diagnostic is oriented by the physical examination, biochemical studies, radiologic, surgical techniques and histological discoveries; that enables us to decide one more accurate sex assignment; the laparoscopy plays an important role, for the direct visualisation of the intra-abdominal gonads, internal genital identification, gonadal biopsy, as well as therapeutic interventions as gonadectomy, orchidopexy and resection of Müllerian remants, replacing totally the laparotomy. The purpose of our job was evaluate the role of the minimal invasive surgical as diagnostic and treatment of the intersex, in nine intersex children treated in our hospital over the last three years.

Disorders of Sex Development↗
PubMed2006

[Reconstruction of velopharyngeal sphincter in secondary Cleft Palate: surgical alternative].

There are numerous surgical procedures for the repair of Cleft Palate (CP). Since 1998, in children with CP we use a modified Wardill-Kilner technique, with a large section of the nasal mucous layer at the level of the muscular insertion on the hard palate and lateral nasopharingeal wall, obtaining a push-back and reorientation of the muscular fibres without dissection, diminishing this way the risks of haemorrhages and fibrosis, simplifying the intervention. It allows a lower operative time and a short internment. The aim of our study was to evaluate the results of this operative procedure specially in the development of the speech in 73 children operated on from 1998 until 2000 in our hospital. We verify a competence of the velopharingeal sphincter with ideal results in speech in 88,8% of the cases.

Cleft Palate↗
PubMed2005

Neuroprotective effect of L-arginine in a newborn rat model of acute severe asphyxia.

The left common carotid artery was ligated in anaesthetized 7-day-old Wistar rats (P7), prior to asphyxia by inhaling 100% nitrogen for 9 min. Pups recovered from asphyxia received i.p. saline (n = 16), or L-Arg 300 mg/kg (n = 14). Pups undergoing sham operation remained as controls (n = 12). At day 14, the amount of surviving or degenerating neurons was quantified under optical microscopy by Nissl technique or by Fluoro-Jade B (FJB) in CA1 area of hippocampus and in parietal cortex. In these areas, asphyxia reduced the neuronal density by 23.6 and 30%, and increased the proportion of degenerating neurons two and four times, respectively. L-Arg administration to asphyxiated pups reduced the neuronal loss and the proportion of degenerating neurons by 50% (p < 0.05). We conclude that L-Arg administration after acute severe asphyxia in newborn rats is neuroprotective, reducing early and delayed neuronal loss.

Animals↗
PubMed2005

Effects of aldehydes on CD36 expression.

INTRODUCTION: During the oil frying process lipid peroxidation compounds are formed. These products can modulate gene expression and alter cellular behaviour. The cellular uptake of oxidized LDL, a key step in the development of atherosclerosis, is mediated by the CD36 scavenger receptor, whose expression is down-regulated by alpha-tocopherol. OBJECTIVE: To determine the effects of water-soluble aldehydes, obtained from thermally oxidized sunflower oil on the expression of CD36 scavenger receptor in human monocytes (THP-1 cells). We also wanted to study the effects of alpha-tocopherol on CD36 expression in the presence of water-soluble aldehydes. MATERIALS AND METHODS: Sunflower oil was heated in a frying pan, at 180--200 degrees C for 40 min, water-soluble aldehydes were isolated, and the content of thiobarbituric acid reacting substances (TBARS) was determined. THP-1 monocytes were cultured in RPMI medium during 24 h and incubated with increasing concentrations of the water-soluble aldehydes (ranging from 0.05 to 1 microM) and with or without 50 microM of alpha-tocopherol. In parallel, THP-1 cells were cultured with the same volume of an extract obtained from non-oxidized oil or distilled water. The CD36 expression at the cell surface was studied with fluorescence-activated cell sorting (FACS). RESULTS: Monocytes incubated in a medium containing water-soluble aldehydes, showed a dose dependent increase in the expression of the CD36 protein on the cell surface, compared to with the control groups. When the cells were treated simultaneously with 50 microM of alpha-tocopherol a significant reduction in the expression of the CD36 protein was observed. CONCLUSION: Water-soluble aldehydes, extracted from thermally oxidized culinary oil, increase the expression of CD36. This effect is partially decreased by the presence of alpha-tocopherol.

Aldehydes↗
PubMed2002

Effects of ergothioneine on diabetic embryopathy in pregnant rats.

The natural antioxidant ergothioneine (2-mercaptohistidine trimethylbetaine) is a fungal metabolite and found in most plant and animal tissues. The effect of ergothioneine on diabetic embryopathy in rats was assessed. Supplementation of diabetic pregnant rats with L-ergothioneine (1.147 mg/kg body weight) daily for the first 11.5 days of pregnancy reduced the rate of embryo malformations, to values similar to the non-diabetic animals. The ergothioneine had no effect on the plasma glucose levels, both in diabetic and control animals. We conclude that the inhibition of the glucose-mediated free radical dependent embryo malformation by ergothioneine is an important antioxidant prophylactic mechanism, which when combined with vitamin E could benefit the management of diabetic embryopathy.

Animals↗
PubMed2000

Estradiol 17beta inhibition of LDL oxidation and endothelial cell cytotoxicity is opposed by progestins to different degrees.

UNLABELLED: Progestins oppose the effects of estrogens in many biological systems, but it is not known if progestins oppose the antioxidant effects of estrogen and to differing degrees. To test these questions, the effects of various sex steroids on LDL oxidation and cytotoxicity were studied in the absence or presence of endothelial cells. Freshly isolated LDL was incubated in the presence of Cu(++) in the absence or presence of cultured bovine aortic endothelial cells in phenol red-free medium and without or with hormones in 0.5% ethanol. The hormones included 17beta-estradiol (E(2)), progesterone (Pg), norgestimate (NGM), levonorgestrel (LNG), and medroxyprogesterone acetate (MPA). LDL oxidation was measured as formation of conjugated dienes, lipid peroxides, and TBARS, and cyotoxicity by tetrazolium salt reduction (MTT reduction). Progestins diminished conjugated diene lag phase, accelerated lipid peroxide and TBARS production in the absence and presence of cells and accelerated cytotoxicity. When E(2) and progestin were incubated with cells at a molar ratio of 1:5, lipid peroxides were reduced from baseline by E(2) alone 31%, E(2)/Pg 29%, E(2)/NGM 16%, E(2)/LNG 9% (all P<0.05 or more) and E(2)/MPA 8% (ns) (E(2) or E(2)E(2)/NGM, E(2)/LNG and E(2)/MPA [P<0.001]; E(2)E(2)/LNG or E(2)/MPA [P<0.05]). MTT reduction followed a similar gradient, greatest with E(2) alone, least with E(2)/MPA. CONCLUSIONS: Progestins promote LDL oxidation and, conjointly, endothelial cell cytotoxicity. Progestins oppose the antioxidant and cytoprotective effects of estrogen when given in combination. MPA and LNG have the strongest prooxidant and cytotoxic effects, which may limit the cardiovascular benefit of estrogen during combined administration in vivo.

Animals↗
PubMed2000

Oxidative damage in pregnant diabetic rats and their embryos.

Free radical mechanisms may be involved in the teratogenesis of diabetes. The contribution of oxidative stress in diabetic complications was investigated from the standpoint of oxidative damage to DNA, lipids, and proteins in the livers and embryos of pregnant diabetic rats. Diabetes was induced prior to pregnancy by the administration of streptozotocin (45 mg/kg). Two groups of diabetic rats were studied, one without any supplementation (D) and another treated during pregnancy with vitamin E (150 mg/d by gavage) (D + E). A control group was also included (C). The percentage of malformations in D rats were 44%, higher than the values observed in C (7%) and D + E (12%) animals. D Group rats showed a higher concentration of thiobarbituric acid reactive substances in the mother's liver, however, treatment with vitamin E decreased this by 58%. The levels of protein carbonyls in the liver of C, D, and D + E groups were similar. The "total levels" of the DNA adducts measured, both in liver and embryos C groups were similar to the D groups. Treatment of D groups with vitamin E reduced the levels by 17% in the liver and by 25% in the embryos. In terms of the "total levels" of DNA adducts, the embryos in diabetic pregnancy appear to be under less oxidative stress when compared with the livers of their mothers. Graziewicz et al. (Free Radical Biology & Medicine, 28:75-83, 1999) suggested "that Fapyadenine is a toxic lesion that moderately arrests DNA synthesis depending on the neighboring nucleotide sequence and interactions with the active site of DNA polymerase." Thus the increased levels of Fapyadenine in the diabetic livers and embryos may similarly arrest DNA polymerase, and in the case of this occurring in the embryos, contribute to the congenital malformations. It is now critical to probe the molecular mechanisms of the oxidative stress-associated development of diabetic congenital malformations.

Adenine↗
PubMed1999

Opposing effects of estrogen and progestins on LDL oxidation and vascular wall cytotoxicity: implications for atherogenesis.

Estrogens are widely regarded as beneficial to arterial wall health. Among the mechanisms of this benefit are antioxidant effects on LDL and the arterial wall. Because progestins oppose the effect of estrogen in several systems, we asked if progestins oppose the antioxidant effect of estrogen. To study this question, LDL and various female sex hormones were incubated alone and combined in the absence or presence of bovine aortic endothelial cells, placental trophoblast, or macrophages, and LDL oxidation and cytotoxicity were quantitated. In the absence of cells, LDL incubated with copper in phosphate-buffered saline enhanced the oxidation of LDL. When 17beta-estradiol was added to this system, an antioxidant effect was observed. Progestins inhibited this protective estrogenic effect. In endothelial cell culture, progestins also opposed the antioxidant effect of estrogen, with the strongest antiestrogenic effect seen with the synthetic progestins, levonorgestrel and medroxyprogesterone acetate (MPA). Endothelial cell cytotoxicity was proportional to the enhanced lipid peroxide formation observed with progestins or estrogen. Similar opposing effects were seen when estrogen and progesterone were added to primary cultures of placental trophoblast or macrophages. Thus, three cell culture systems modeling circulating arterial blood contact with cell surfaces demonstrated opposing effects of estrogens and progestins on LDL oxidation and cell cytotoxicity. These studies are in keeping with published reports that female sex steroids influence LDL oxidation in vivo and consequent arterial wall injury.

Arteriosclerosis↗
PubMed1999

Alpha-tocopherol concentration in fetal and maternal tissues of pregnant rats supplemented with alpha-tocopherol.

We wanted to determine whether alpha-tocopherol supplementation to pregnant rats could increase the concentration of alpha-tocopherol in maternal and fetal plasma and tissues. Pregnant rats were treated with alpha-tocopherol on days 18 and 19 gestation and studied at day 20. A control group was studied in parallel. Treatment of pregnant rats with alpha-tocopherol increased its concentration in maternal and fetal plasma, in all maternal plasma lipoprotein fractions, in maternal and fetal liver and in the placenta. The fetal and maternal concentration of alpha-tocopherol were positively correlated.

Animals↗
PubMed1998

LDL oxidation and human placental trophoblast and macrophage cytotoxicity.

We have previously shown that LDL is oxidized by placental cells in primary tissue culture and that this process causes cytotoxicity proportional to LDL oxidation in the presence of sex steroid hormones. Here we describe further experiments linking LDL oxidation to placental cell cytotoxicity. Trophoblast and macrophages were isolated from healthy elective caesarean section placentas by enzymatic digestion and separated by centrifugation on a 40% Percoll gradient and maintained in primary culture for up to 5 days. LDL was oxidized by exposure to 5 microM CuCl2, cells were incubated in the absence of albumen to favor oxidation, and cytotoxicity was measured by 51Cr release from prelabelled cells and cell protein content. Native LDL was oxidized by both cell types with a 10%-50% increase in lipid peroxides and an approximately 4-fold increase in TBARS formation. Increasing concentrations of native LDL and oxidized-LDL increased 51Cr release and diminished protein content in cells incubated in HAM's F-10 medium. Addition of 5 microM Cu2+ augmented cytotoxicity of LDL in macrophage and trophoblast culture, but more in macrophages than trophoblast. Cytotoxicity was diminished by adding 0.001-0.1 mM EDTA to the system, diminishing 51Cr release from 91 +/- 0.5 to 40.8 +/- 1.0% in macrophages and 54.2 +/- 1.2 to 33.1 +/- 1.3% in trophoblast (P < 0.001 in both instances). Similarly, the absence of transition metal ion in culture (MEM medium) blocked an increase in 51Cr release compared to its presence (HAM's F-10 medium). An antioxidant, butylated hydroxytoluene, diminished 51Cr release and LDL electrophoretic mobility in HAM's F-10 medium in placental macrophage culture. LDL oxidation injures placental macrophages and trophoblast, the former more than the latter. The process is LDL- and transition metal ion-dependent and is inhibited by antioxidant. This model of LDL oxidation and placental cell damage in vitro provides a basis for studying mechanisms of placental dysfunction and senescence in human pregnancy.

Antioxidants↗
PubMed1997

Simultaneous determination of vitamins A and E in rat tissues by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method to determine vitamins A, Ap and E simultaneously was developed with direct extraction of vitamins from rat tissues with n-hexane and probe sonicating. The dry residue was redissolved in chloroform-methanol. Vitamins A and Ap were detected by UV-Vis and vitamin E by fluorescence. Vitamin K, used as internal standard, was detected both the UV-Vis and by fluorescence. Standards and samples were checked for linearity giving correlation coefficients that were higher than 0.99 in the concentration range of 3.1-9.4 for vitamin A, 8.2-24.7 for vitamin Ap and 0.6-1.7 nmol/g in the case of liver extracts and 0.5-3.0 nmol/g in the case of placenta. The inta-assay precision (R.S.D) varied between 1.48 and 7.25, whereas inter-assay precision was between 4.99 and 7.03. Recoveries ranged between 94 +/- 8 and 107 +/- 5%. Results from the application of this method to different rat tissues having wide range of vitamin content are presented.

Animals↗
PubMed1997

17beta-Estradiol, progesterone, and testosterone inversely modulate low-density lipoprotein oxidation and cytotoxicity in cultured placental trophoblast and macrophages.

OBJECTIVES: We have previously shown that low-density lipoprotein oxidation is diminished by 17beta-estradiol and enhanced by progesterone and testosterone. In these experiments we wished to learn whether sex hormone effects on low-density lipoprotein oxidation alter placental cell viability in primary tissue culture. STUDY DESIGN: Primary tissue culture of human term placental cells was performed. RESULTS: Addition of 17beta-estradiol decreased low-density lipoprotein oxidation (measured as lipid peroxides, thiobarbituric acid-reacting substances, and low-density lipoprotein electrophoretic mobility) and placental cell toxicity (measured as chromium 51 release) with maximum reductions of 28% (macrophages) (p < 0.05) and 26% (trophoblasts) (p < 0.01). Conversely, progesterone and testosterone increased low-density lipoprotein oxidation and chromium 51 release, the latter a maximum of 28% and 18%, respectively, for progesterone and testosterone in macrophages (p < 0.05 in both instances) and 23% in trophoblasts (p < 0.05, testosterone only). Collectively, cytotoxicity was proportional to low-density lipoprotein oxidation and estradiol, progesterone, and testosterone concentrations. CONCLUSIONS: Estradiol inhibits placental macrophage- and trophoblast-mediated low-density lipoprotein oxidation and cytotoxicity, whereas progesterone and testosterone promote these effects. Sex steroid hormones may modulate the effects of oxidative stress on placental function in pregnancy.

Cell Death↗
PubMed1997

Antioxidant and prooxidant effects of ascorbic acid, dehydroascorbic acid and flavonoids on LDL submitted to different degrees of oxidation.

UNLABELLED: Although a high intake of antioxidants may decrease the risk of developing cardiovascular diseases, under certain circumstances they may promote free radical generation and lipid peroxidation. The objectives of the present study were to determine the antioxidant effects of ascorbic acid (AA), dehydroascorbic acid (DHA) and flavonoids on LDL submitted to different degrees of oxidation. LDL was submitted to oxidation with CuCl2 (2.4 microM). Before or at different times after the propagation of the oxidation process, 28 microM (5 micrograms/ml) of either AA or DHA or 5 micrograms/mL flavonoids extract were added. Alpha-tocopherol, conjugated dienes, thiobarbituric acid reacting substances (TBARS) and LDL electrophoretic mobility were determined as indices of LDL oxidation. The presence of any of the three antioxidants from the onset of the incubation delayed the oxidation process. However, the addition of both DHA and flavonoids to the oxidation process when it was already initiated and alpha-tocopherol consumed, accelerated the oxidation. In contrast, AA delayed the oxidation process even when added after alpha-tocopherol was consumed. Nevertheless, it also accelerated LDL oxidation when added during the propagation phase of the oxidation process. IN CONCLUSION: although AA, DHA and flavonoids delay LDL oxidation when added before the initiation of the process, they accelerate the process if added to minimally oxidized LDL.

Adult↗
PubMed1996

Teratogenic effects of diabetes mellitus in the rat. Prevention by vitamin E.

We wanted to determine whether administration of vitamin E could reduce the production of free radicals which could play a role in the teratogenic effects of diabetes mellitus. Diabetes was induced in Wistar rats by the intravenous administration of streptozotocin. The animals were divided into six groups: one with no supplement (D) and two, supplemented during pregnancy either with oral vitamin E (150 mg/day) (D + E) or with a placebo (safflower oil) (D + O). Three other groups were kept under the same conditions, but were treated with insulin: D + I, D + I + E and D + I + O. There were three groups of matched controls: C, C + E and C + O. All animals were killed on day 11.5 of pregnancy. In C animals the percentages of reabsorptions and malformations were 1.3 and 2%, respectively, compared with 23.6, 24.3, 6.2 and 13.2%, respectively in D and D + I groups. The crown-rump length, number of somites, and protein and DNA content were higher in C animals than in the diabetic rats, independent of insulin treatment. When vitamin E was administered no changes in these parameters were observed in C and D + I animals; however, in the D mothers it reduced the rate of embryo malformations to 4.6% and increased the crown-rump length and the number of somites. However, vitamin E did not modify the protein and DNA content and the percentage of reabsorptions. In conclusion, administration of vitamin E to diabetic animals decreases the rate of embryo malformations and increases their size and maturation, supporting a role for free radicals in the teratogenic effects of diabetes.

3-Hydroxybutyric Acid↗
PubMed1996

In vitro effects of a flavonoid-rich extract on LDL oxidation.

Flavonoids are phenolic compounds of vegetable origin with antioxidant effects. The present study aimed to determine their properties as LDL antioxidants. LDL were incubated with increasing concentrations of flavonoids (0-16 micrograms/ml) and LDL oxidation was started by adding CuCl2 (2 microM) to the media. When flavonoids were present in the media, vitamin E consumption, the lag phase of conjugated diene formation, LDL electrophoretic mobility in agarose gels and the appearance of thiobarbituric acid reacting substances (TBARS) were delayed in a concentration-dependent manner. To determine whether flavonoids could terminate LDL oxidation once initiated, two sets of experiments were performed. In the first, LDL oxidation was initiated as described above. At 2 or 4 h of incubation, flavonoids were added (4 micrograms/ml) and their effect compared to samples where butylated hydroxytoluene or EDTA were added. At 5 h, in the LDL samples where flavonoids were added, the electrophoretic mobility and TBARS production were the same as those present in LDL samples incubated for the whole period in the absence of flavonoids. However, when either butylate hydroxytoluene or EDTA was added, as would be expected, the LDL oxidation process was completely arrested as shown by a reduction in the appearance of TBARS and a lower LDL electrophoretic mobility. In the second experiment, LDL oxidation was initiated as described above and at 0, 10 and 20 min, flavonoids were added (4 micrograms/ml). When vitamin E was still present in the LDL solution, the flavonoids were able to both increase the lag phase in the formation of conjugated dienes and to delay the consumption of vitamin E. The present results show that in vitro, flavonoids prevent LDL oxidation in a concentration-dependent manner, delaying the consumption of vitamin E, but they cannot terminate or delay LDL oxidation once vitamin E in LDL is consumed.

Antioxidants↗
PubMed1995

Metabolism of modified LDL by cultured human placental cells.

UNLABELLED: All major classes of normal circulating lipoproteins can be metabolized by human placental cells. However, the metabolism of abnormal or modified lipoproteins has been little studied. We therefore investigated whether placental cells metabolize acetylated low density lipoprotein (ac-LDL) or oxidatively-modified LDL (ox-LDL), both of which are metabolized by scavenger receptors, and if so, whether modified LDL stimulates progesterone secretion as does normal LDL. Placental macrophages and trophoblasts were isolated on a 40% Percoll gradient after enzymatic digestion. The cellular uptake and degradation of [125I]-ac-LDL was 20-fold higher than [125I]-LDL in both macrophages and trophoblasts. Both cell types demonstrated high affinity and saturable degradation. Similarly, increased esterification of [14C]-labelled oleic acid to cholesterol was observed when cells were incubated with ac-LDL vs. LDL. Uptake of ac-LDL by trophoblasts also was demonstrated by colocalization of fluorescently labelled ac-LDL and fluorescent antibodies specific for trophoblasts. Similar colocalization of fluorescent ac-LDL and fluorescent anti-macrophage specific epitopes was seen in macrophages. Uptake and degradation of [125I]-ac-LDL by placental cells was inhibited by increasing concentrations of unlabelled ac-LDL or fucoidin but not LDL, indicating uptake by a scavenger receptor. Both unlabelled ac-LDL and ox-LDL inhibited uptake of [125I]-labelled ox-LDL, suggesting uptake by a common mechanism. Although secretion of progesterone by trophoblasts was stimulated by incubation with LDL, progesterone secretion by trophoblasts was not stimulated by ac-LDL and only minimally stimulated by ox-LDL. CONCLUSIONS: Scavenger receptors are present in human placental trophoblasts as well as macrophages. Scavenger receptor activity greatly exceeds that of LDL receptor activity in both cell types. However, cholesterol assimilated via the scavenger receptor pathway appears to be disconnected from endocrine steroidogenesis in trophoblasts. Thus, we hypothesize that scavenger receptors function in trophoblasts to degrade modified lipoproteins and prevent toxic effects on placental cellular function and fetal growth and development.

Cells, Cultured↗