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Y Fernandez

Publications and source records attributed to Y Fernandez.

54 records · Page 3Linked to original sources

Effects of polychlorinated biphenyls on liver regeneration in the rat: influence of position and degree of chlorination.

The effects of PCBs, administered intragastrically, were studied on partially hepatectomized (70%) rats. Seven days after hepatectomy, a relationship was noted between the increase in the degree of chlorination of the biphenyl molecule and the hypertrophy and lipid accumulation in the liver. When the 3' and 4' positions are chlorinated, the relationship still holds but, for a constant number of chlorine atoms, the intensity of the effects are decreased. Fourteen days after hepatectomy, there was only a significant difference in the case of decachlorobiphenyl and Phenoclor DP5, for which the hypertrophy is accompanied by hyperplasia. The relationships are discussed between the chemical structure of the PCBs, their metabolization, their toxicity, and the reversibility of their effects.

Animals↗

Carbaryl tricompartmental toxicokinetics and anticholinesterase activity.

The blood kinetics of carbaryl and the inhibition of plasma acetylcholinesterases were followed for 24 h after administration of 20 mg/kg [14C]carbaryl (0.17 microCi/mg). The kinetics of the radioactivity attributed to unaltered carbaryl is bi-exponential whereas that of the total 14C activity is tri-exponential. The kinetics were treated with open 2- and 3-compartment models respectively. The exchange rate constants between the various compartments as well as the elimination constant (expressed in h-1) were found to be: k12 = 1.93, k21 = 1.18 and k10 = 2.46 (2-compartment model) and k'12 = 18.65, k'21 = 13.90, k'13 = 1.14 k'31 = 0.125 and k'10 = 0.672 (3-compartment model). The 3-compartment model demonstrates the persistence in the blood of 14C activity which correlated with plasma acetylcholinesterase inhibition.

Acetylcholinesterase↗

[Radioimmunoassay of trypsin in dried blood. Importance for the neonatal detection of cystic fibrosis (author's transl)].

The demonstration of very high levels of immunoreactive trypsin in the blood of newborn infants with cystic fibrosis has provided a new way of detecting the disease soon after birth. A radioimmunoassay of trypsin in the eluate of blood dried on filter paper has now been developed. The sensitivity and accuracy of the method, as well as the good correlation observed between the values obtained and those of the conventional plasma assay, indicate that it is reliable and well adapted to the newborn. The new assay can easily be inserted into the present system of neonatal disease detection. A preliminary assessment of more than 5,000 tests enables the authors to report an early diagnosis of proven cystic fibrosis and to discuss an essential aspect of mass-detection methods: the indicence of false-positive results.

Cystic Fibrosis↗

Evaluation of the toxic risk of accumulated DDT in the rat: during fat mobilization.

The effects of greatly reduced food intake were investigated in rats which had accumulated three times as much DDT as rats killed with a single dose approaching LD50. DDT and its metabolites mobilized more quickly than the fat deposits. The hypertrophy of the liver due to DDT decreased during food restriction and demonstrated the existence of a large detoxication capacity shown through the high metabolism of the pesticide. The disappearance of p,p' DDE was most rapid, followed by p,p' DDD then p,p' DDT; they did not accumulate in the fat reserves. The half-life of the pesticide, which is normally three months in the rat, was reduced to five days under the experimental conditions. In spite of rapid mobilization, no major toxic signs were detected from either nutritional, physiopathological, or biochemical examinations.

Animals↗

Variations of the digestive absorption kinetics of carbaryl with the nature of the vehicle.

Blood kinetics of 1-naphthyl-N-methyl[14C] carbamate were determined after intravenous injection in DMSO, and after intragastric and intraduodenal administration in DMSO, oil, gum tragacanth and milk. The acetylcholinesterase inhibition and the level of 14C-activity were both determined in the blood over various periods of time. The values of the absorption rate constants after intragastric and intraduodenal administration were found to be: 0.5 h(-1) and 7 h(-1) with DMSO, 0.6 h(-1) and 0.42 h(-1) with oil, 0.13 h(-1) and 0.22 h (-1) with gum tragacanth and 0.10 h(-1) with milk. Appearance of the toxic effect (the inhibition of the acetylcholinesterases) was closely related to the absorption rate constants which themselves depend on the administration vehicle employed.

Animals↗

Microsomal membrane peroxidation by an Fe3+/paraquat system. Consequences of phenobarbital induction.

Descriptions of the effects of paraquat (P2+) on the peroxidation of liver microsomes are very divergent. Therefore, the presence of ferric iron in the medium and the activity of microsomal mixed-function oxidase system are two factors that we have taken into consideration to explain the discrepancies. The results showed that 100 microM P2+ potentializes the slight production of MDA induced by low concentrations of Fe3+ (< or = 15 microM). In these conditions, P+., arising from the one-step reduction of P2+ by NADPH-cytochrome C reductase, could reduce Fe3+ and cause the formation of species that initiate peroxidation. However, unlike the results obtained with CBrCl3, for animals induced by phenobarbital (Ph), the production of MDA in the presence of FeCl3 and of P2+ was weaker than for the controls. The establishment of a new Fe3+/Fe2+ equilibrium owing to increased production of P+. could be responsible.

Animals↗

Catechin protection of 3T3 Swiss fibroblasts in culture under oxidative stress.

The effects of catechin, a well-known in vitro antioxidant, on 3T3 Swiss fibroblasts are studied under different conditions of oxidative stress leading to cell proliferation or cytotoxicity. Various levels of reactive oxygen species (ROS), generated extracellularly by the xanthine-xanthine oxidase (X-XO) system, are at the origin of the biphasic effect on DNA synthesis by 3T3 Swiss fibroblasts. The addition of 10(-2) U XO/mL, in the absence of exogenous X, catalyzes the production of low levels of O2-. and H2O2 in the extracellular medium, which stimulate DNA synthesis and cell division. The increase in the level of ROS, by addition of increasing X concentrations, did not enhance this effect proportionally. On the contrary, high levels of ROS inhibit DNA synthesis, the cytotoxicity induced being proportional to the level of H2O2 generated by the enzyme system. Catechin does not significantly modify DNA synthesis induced by low levels of ROS, but protects in a dose-dependent manner against the cytoxicity of high levels of ROS.

3T3 Cells↗

Phospholipid fatty acid composition affects enzymatic antioxidant defenses in cultured Swiss 3T3 fibroblasts.

The aim of this work was to study the adaptation of enzymatic antioxidant cell defense to the nature of the membrane polyunsaturated fatty acids (PUFA). 3T3 Swiss fibroblasts were grown for 5 days in a medium supplemented with 50 microM linoleic acid (LA) or eicosapentaenoic acid (EPA) and compared to control cells (C). The phospholipid fatty acid content was evaluated: LA were enriched in n-6 PUFA (27.8%) in comparison to C (6.7%) or EPA (5.6%); EPA were enriched in n-3 PUFA (26.2%) in comparison to LA (4.4%) or C (4.6%). The fatty acid double bond index (DBI) increased from C to LA and EPA. The activities of the three key enzymatic antioxidant defenses, SOD, GPx and GST, increased with the degree of unsaturation of the phospholipid fatty acids. In the cells with fatty acids that are very sensitive to oxidative stress, the higher activities of SOD and GPx might act to limit the initiation of lipid peroxidation and the higher activities of GST and GPx to decrease the toxic effects of the various species produced from lipid degradation.

3T3 Cells↗

Total parenteral nutrition decreases liver oxidative metabolism and antioxidant defenses in healthy rats: comparative effect of dietary olive and soybean oil.

BACKGROUND: Total parenteral nutrition (TPN) is used for critically ill patients undergoing surgery, after trauma, or during disease conditions that favor oxidative stress. We studied the effect of TPN on liver oxidative metabolism and antioxidant defenses in rats, and we compared the effect of soybean oil- and olive oil-based diets. METHODS: Seven-week-old rats (n = 28) were divided into four groups. Two experimental groups received a TPN solution containing soybean oil (TPN-S) or a mixture of olive/soybean oil, 80/20 (TPN-O), IV for 6 days. Orally fed animals received a solid diet including soybean oil (Oral-S) or olive/soybean oil, 80/20 (Oral-O). The following parameters were measured: DL-alpha-tocopherol, vitamin A, malondialdehyde and thiobarbituric acid reactive substances (MDA-TBARS), and total radical-trapping antioxidant parameter (TRAP) in serum; DL-alpha-tocopherol, vitamin A, glutathione (GSH), and catalase (Cat) activity in liver homogenate; fatty acids from phospholipid, cytochrome P-450 content, NADPH-cytochrome c2 reductase activity in liver microsomes; superoxide dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) in liver cytosol. RESULTS: The soybean or olive oil diets modified the liver microsomal fatty acid phospholipid composition, but the unsaturation index remained unchanged. TPN specifically increased the saturation of the membrane. The cytochrome P-450 level and the NADPH-cytochrome c2 reductase, SOD, Gpx, Cat, and GST activities were unchanged by soybean oil or olive oil diet but decreased receiving TPN. CONCLUSIONS: In rats, TPN decreased the liver oxidative metabolism and enzymatic antioxidant defenses. This may be related to saturation of the liver microsomal fatty acids.

Administration, Oral↗

[Neonatal diagnosis of hypothyroidism by measurement of TSH levels: results in a series of 1880 cases from the University Hospital Center in Caen (author's transl)].

Early substitutive hormonal treatment for congenital hypothyroidism is the main factor affecting the prognosis of mental abnormalities. Therapy should be instituted in the first few weeks of life but clinical diagnosis is usually very difficult at this stage and biological criteria have to be used as a basis for establishing the diagnosis during the neonatal period. For this reason, TSH levels were measured in 1880 babies on the 4th day of life. This enabled a diagnosis of thyroid agenesia to be made in a case where no tangible clinical signs were present, and treatment could be started on the 12th day of life. Furthermore, two cases of hypothyroidism from iodine overdosage during amniography were discovered and early treatment instituted. The results of this study, which was limited to only one maternity unit, demonstrate the value of systematic diagnostic procedures for congenital hypothyroidism. It also underlines the danger of iodine overdosage during foetal life which could contra-indicate the use of amniography.

Congenital Hypothyroidism↗