Biomedical subjects

H Faure

Publications and source records attributed to H Faure.

At least 37 records · Page 2Linked to original sources

PubMed1998

Regional distribution of Sonic Hedgehog, patched, and smoothened mRNA in the adult rat brain.

In vertebrates, Sonic Hedgehog (Shh), Desert Hedgehog (Dhh), and Indian Hedgehog (Ihh) genes encode a family of morphogen proteins that are implicated in a wide range of signaling activities, particularly during embryonic development. These secreted proteins are proposed to mediate their effects on target cells by interacting with their putative receptor, Patched (Ptc), and with a seven-pass transmembrane protein, Smoothened (Smo). However, the roles that these signaling molecules may play in adult tissues, particularly in brain, are not yet clearly defined. Therefore, we investigated the expression of these genes in adult rat tissues. Northern blot analysis revealed expression of Shh, Dhh, and Ihh genes in peripheral tissues, whereas Shh transcript was also identified in brain. It is interesting that northern blot analysis with probes derived from the mouse Ptc and Smo genes revealed the expression of a 7.9-kb and a 3.7-kb transcript, respectively, in all brain tissues examined. In situ hybridization experiments using specific digoxigenin-labeled riboprobes showed expression of Ptc and Smo transcripts in discrete brain areas. Shh-positive cells were observed in restricted regions of the brain. Within the cerebellum, Shh, Ptc, and Smo transcripts were colocalized in the Purkinje cell layer. These data suggest that, besides its roles in determining cell fate and patterning during embryogenesis, the hedgehog signaling pathway may have also important roles in the adult brain.

Age Factors↗

PubMed1998

Influence of the 'directions for use' on positivity rates of the Hemoccult II test.

OBJECTIVE: A concise, detailed, and complete instruction sheet is indispensable for adequate completion by the users of a product. This sheet should be enclosed in the envelope which contains Hemoccult II slides. The authors found that the instructions provided by the French manufacturer were unsatisfactory. They designed a short and simple notice, adequately detailed to be understandable by all volunteers and to obtain satisfactory stool smears. Positivity rates of Hemoccult II performed with the manufacturer's notice were compared to those obtained with Hemoccult II performed with the authors' instructions. METHODS: This study was made during the third screening campaign carried out by the Office Departemental de Lutte contre le Cancer (ODLC). This screening programme only concerned women 59 to 69 years of age. Six thousand three hundred and ninety-two Hemoccult II containing the manufacturer's instructions were received at the laboratory during March, April, May, June and July 1996, and 2633 Hemoccult II containing the ODLC instructions during March, April, May, June and July 1997. All Hemoccult II were developed and read by one trained technician in the Biochemistry Laboratory (Grenoble University Hospital). RESULTS: The two populations, studied in 1996 and 1997, were strictly comparable in terms of age and number of previous screenings. Out of 6392 Hemoccult II containing the manufacturer's instructions, 157 (2.5%) were found positive, as compared to 36 (1.4%) Hemoccult II out of 2633 which contained the authors' instructions. This difference is highly significant (P = 0.001). CONCLUSION: The directions for use provided with Hemoccult II had a crucial influence on positivity rates, and therefore on the cost of screening. The instruction sheet provided by the French manufacturer is not satisfactory as it contains too much needless information, while several important pieces of advice are missing.

Aged↗

PubMed1998

Urine 8-oxo-7,8-dihydro-2-deoxyguanosine vs. 5-(hydroxymethyl) uracil as DNA oxidation marker in adriamycin-treated patients.

We measured the base 5-(hydroxymethyl) uracil (HMUra) and the nucleoside 8-oxo-7,8-dehydro-2'-deoxyguanosine (8-oxo-dGuo) in urine of adriamycin-treated cancer patients. Adriamycin has been shown to generate oxygen free radicals by various mechanisms. HMUra and 8-oxo-dGuo are two known lesions of DNA, produced by oxygen free reaction on thymine and 2'-deoxyguanosine, respectively. HMUra was measured by GC-MS/isotopic dilution and 8-oxo-dGuo by HPLC/EC, both after prepurification by semipreparative HPLC. Here we report the results of a study involving 20 cancer patients treated with flash doses of ADR. We found that urine HMUra is significantly increased (HMUra (nmol/24h): 80.8 8.44 vs. 98.7+/-6.87; p < 0.01) 24h after administration of the drug, while 8-oxo-dGuo did not show any significant variation. Urine HMUra seems to be a suitable short-term marker of DNA alterations by oxygen free radicals.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

5-Hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vitamins in adriamycin-treated patients.

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly .OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.

Adult↗

PubMed1996

Rapid high-performance liquid chromatographic assay for salicylic acid in plasma without solvent extraction.

The in vivo measurement of highly reactive free radicals, such as the hydroxyl radical (oOH), in humans is very difficult, if not impossible. Specific markers, based on the ability of oOH to attack aromatic molecules and produce hydroxylated compounds, are under investigation. In vivo radical metabolism of salicylic acid produces two main hydroxylated derivatives: 2,3- and 2,5-dihydroxybenzoic acid (DHBA). The measurement of 2,3-DHBA, following oral administration of salicylic acid or its acetylated form (aspirin), is proposed for the assessment of in vivo oxidative stress. The intensity of oxidative stress is a function of the ratio of dihydroxylated derivatives to salicylic acid rather than the absolute dihydroxylated derivatives levels. Consequently, a simple, accurate, and sensitive assay of the salicylic acid level in plasma is needed to investigate the in vivo free radical production. In this work, a rapid and sensitive method is presented that is useful for the quantitation of salicylic acid in biological fluids. The methodology uses high-performance liquid chromatography with spectrophotometric detection for the identification and quantitation of salicylic acid without organic extraction. A detection limit of less than 5 mumol is achieved with spectrophotometric detector responses that are linear over at least 6 orders of magnitude. Plasma concentrations of salicylic acid determined by the present technique are reported following the administration of 1000 mg aspirin in 20 healthy subjects.

Chromatography, High Pressure Liquid↗

PubMed1996

[Simultaneous screening of cancers of the breast, cervix, colon and rectum. The Isère experience].

The mass screening program for cancer in the Isere department offers women between 50 and 69 years a medical consultation and three tests: mammography for breast cancer screening, Pap smear for cervical cancer screening, and hemoccult for colorectal cancer. During the first round, 29,570 women took part in the program, 21% had a mammography, 20% Pap smears and 25% a hemoccult. In breast cancer screening, the rate for further examination was 11.9%, the breast cancer detection rate was 5.4 per 1,000 women screened and the detection rate of invasive tumor < or = 10 mm: 2.0 per 1,000. In cervical cancer screening, the rate of abnormal examinations was 1.2%. The cervical cancer detection rate was 1.5 per 1,000. The rate of positive hemoccult was 2.7% and the rate of colorectal cancers and polyps 10 mm or larger was 2.7 per 1000. Results of screening are satisfying, but compliance rate is too low. Acceptance rate must be examined in following rounds.

Aged↗

PubMed1994

Longitudinal changes in serum zinc concentration and distribution after acute myocardial infarction.

The authors studied the changes in serum zinc concentration and distribution during the 15 days following acute myocardial infarction in 21 patients. The method is based on ultrafiltration and electrothermal atomic absorption spectrometry. It is rapid and needs only 2.5 ml of serum. Serum and erythrocyte copper and zinc, serum zinc-binding ligands and serum enzyme activities were also determined. Serum zinc (P < 0.00001) and exchangeable zinc (mainly albumin-bound zinc, P = 0.01) declined within the first 3 days and then returned gradually to reference ranges. Exchangeable zinc was correlated with transthyretin (P = 0.00001) and total serum zinc (P < 0.00001). Exchangeable zinc accounted for virtually all of the differences in total serum zinc concentration after myocardial infarction. This result could be related to an increase of zinc uptake by tissues. Therefore, studies are needed to evaluate whether zinc supplementation in the early stages of acute myocardial infarction might improve prognosis.

Adult↗

PubMed1994

Effect of taurine, L-glutamine and L-histidine addition in an amino acid glucose solution on the cellular bioavailability of zinc.

Radioactive zinc was used to study the effect of a binary parenteral nutrient solution, composed of amino acids and glucose, on zinc uptake by fibroblasts. The influence of addition of taurine, L-glutamine and of the increase in L-histidine content of the admixture was assessed. The pure mixture was highly toxic for cells and so it was diluted 1/5 in tyrode buffer with 2% albumin. As compared with cells incubated in the buffer containing albumin, zinc absorption was significantly higher (P < 0.05) in the presence of the amino acids of the mixture. Amino acids thus increased bioavailability by displacing zinc bound to albumin. When the histidine concentration in the nutrient medium (4.2 mM) was doubled, inhibition was noted after 30 min of incubation and zinc uptake thereafter remained comparable to that in histidine-free medium. The addition of glutamine (4.2 mM), usually not present in binary mixtures, resulted in significant differences as compared with glutamine-free control medium. Taurine (0.8 mM), led to a constant increase in zinc uptake by fibroblasts as compared with that obtained with taurine-free mixture. However, ultrafiltration showed that taurine was not able to displace zinc from albumin.

Biological Availability↗

PubMed1994

Zinc changes in blood and urine during cyclic parenteral nutrition: relationships with amino acid metabolism.

Serum Zn, ultrafiltrable Zn and amino acids in serum and urine samples of twenty-seven patients receiving cyclic (12 h/24 h) parenteral nutrition were measured. These samples were collected in patients after a 12 h period of parenteral nutrition, and in the evening after 12 h without parenteral nutrition. The same determinations were performed in ten control subjects who followed the same sampling scheme. Total serum ultrafiltrable Zn showed no significant variations in the patients during parenteral nutrition, and was not significantly different in the two groups although the proportion of the Zn present in the ultrafiltrable fraction was elevated. Serum cystine levels were significantly higher (P = 0.05) in the patients than the control subjects, and cystine excretion was also higher in patients (P < 0.05) and increased after parenteral nutrition (56.0 (SE 6.5) v. 147.1 (SE 20.6) mumol/12 h; P < 0.001). Histidine levels did not vary significantly in serum after parenteral nutrition and were not different in the patients in comparison with the control subjects. Histidine excretion was not different in the two groups but increased significantly during parenteral nutrition (P < 0.05). Serum albumin was significantly depressed in the patients compared with the control subjects (45.3 (SE 1.5) v. 33.9 (SE 1.5) g/l; P < 0.001). These results suggest that cystine infusion and excretion relate to the changes occurring in serum Zn and in urinary Zn excretion.

Adolescent↗

PubMed1993

Blood and liver lipid peroxide status after chronic ethanol administration in rats.

During the last decades a vast number of reports have aimed at elucidating the mechanisms behind alcohol-related organ injury, but the manner in which ethanol induces, e.g., liver damage is still an enigma. Increased oxidative stress has been put forward as one possible mechanism behind alcohol-related tissue damage. This paper focuses on the effect of chronic ethanol consumption on antioxidant status and lipid peroxide levels in blood and liver of rats. Alcohol was given twice daily in a total dose of 5 g ethanol/kg body wt. per day divided into two 2.5 g ethanol/kg body wt. doses as a 50% water solution, by gavage over 4 weeks. Chronic ethanol ingestion led neither to a significant change in lipid peroxide formation nor to a significant change in enzymatic antioxidant activities. Only concentrations of oxidized glutathione and of other non-enzymatic antioxidant such as vitamin E showed a tendency to decrease after alcohol application. The data presented could serve to emphasize no involvement of free radical-induced lipoperoxidation in the pathogenesis of ethanolic liver diseases.

Alcoholism↗

PubMed1993

Gas chromatographic-mass spectrometric determination of 5-hydroxymethyluracil in human urine by stable isotope dilution.

A method for the determination of 5-hydroxymethyluracil in urine is described. 5-Hydroxymethyluracil was extracted by reversed-phase chromatography and quantified by gas chromatography-mass spectrometry as tert.-butyldimethylsilyl derivative. Since natural 5-hydroxymethyluracil contained ca. 22% of M + 2 species, an internal standard consisting of [1,3-15N2,5-2H2]hydroxymethyluracil was used to correct losses during extraction, evaporation and derivatization. Between-run precision of this method was 7.79%, and concentrations as low as 1.87 nM could be measured. This sensitivity and precision could not be obtained with trimethylsilyl derivatives.

Gas Chromatography-Mass Spectrometry↗

PubMed1993

Protective effect of selenium and zinc on UV-A damage in human skin fibroblasts.

Ultraviolet A radiation participates in cytotoxicity and carcinogenesis of the skin by a mechanism involving the generation of reactive oxygen species. Endogenous antiradical defense systems utilize metalloenzymes including Se-dependent glutathione peroxidase and Cu and Zn superoxide dismutase. The aim of the present work was to determine the protective effect of two trace elements, Se and Zn, on cultured human diploid fibroblasts exposed to UV-A radiation (broad-spectrum source with a maximum intensity at 375 nm). Selenium in the culture medium (0.1 mg/L) in the form of sodium selenite increased the synthesis and activity of glutathione peroxidase by 60.5% in the absence of exposure to UV-A radiation and by 35% after irradiation with 5 J/cm2 (P = 0.043). The presence of this element significantly increased the survival of UV-A-irradiated fibroblasts (P < 0.0001). This confirms the essential role of Se in the detoxifying activity of the enzyme. In addition, thiobarbituric acid-reacting substances (TBAR), which are lipid peroxidation markers, decreased in the presence of exogenous Se: -19% and -22% without irradiation and after irradiation with 5 J/cm2 (P = 0.056). When Zn was added at the dose of 6.5 mg/L as ZnCl2, fibroblasts subjected to oxidizing stress induced by UV-A were protected from cytotoxicity (P < 0.0001). The TBAR production decreased significantly: -33% without irradiation and -34% after irradiation with 5 J/cm2 (P = 0.008). Superoxide dismutase activity, however, decreased after supplementing with Zn: -26% without irradiation and -20% after UV-A irradiation (P = 0.017). The antioxidant properties of Zn are thus apparently independent of superoxide dismutase activity.

Cell Division↗

PubMed1993

Measurement of oxidative base damage to DNA by using HPLC-32P-postlabelling and GC/MS-selective ion monitoring assays.

A 32P-postlabelling assay has been developed for singling out specific oxidized base lesions. Emphasis was placed on the quantitative aspect and the accuracy of the assay, which require the use of calibration curves and microreactions, respectively. The method was successfully applied to the detection and the measurement of adenine N1-oxide and 5-hydroxymethyluracil in cells exposed to agents inducing oxidative stress including H2O2 and UV-A radiation. The sensitivity of the assay allows the detection of one lesion in 10(6) normal bases in 1 microgram of DNA. The GC/MS method when coupled to the selective ion monitoring (SIM) technique is about twenty times less sensitive, even for suitable substrates such as 5-hydroxymethyluracil and 5-hydroxyuracil, than the 32P-postlabelling assay. However, the former assay is much easier to apply, even though a derivatization step is necessary, and provides unambiguous structural information on the compound to be measured. Accurate quantitative measurements can be obtained when stable, isotopically labelled standards are available.

Chromatography, High Pressure Liquid↗

PubMed1993

Effect of double-blind crossover selenium supplementation on biological indices of selenium status in cystic fibrosis patients.

Twenty-seven cystic fibrosis patients received selenium supplementation (2.8 micrograms of sodium selenite per kilogram of body weight per day) or a placebo. This 5-month trial was conducted as a double-blind, placebo-controlled study. After an interval of 2 months, treatments of the two groups were interchanged (crossed over) for another 5-month period. A group of healthy subjects, living in the same area, was investigated simultaneously. No selenium deficiency was found either in plasma or in erythrocytes before the supplementation. This result was inconsistent with a previous study performed in 1988 in our laboratory. This change in selenium status can be explained by progress in the nutritional nursing care of children and by the addition of selenium to the diet. During the study, selenium concentrations in plasma decreased when patients received placebo treatment and increased during selenium intake. In one of the two groups a similar variation was found for glutathione peroxidase activities in plasma and erythrocytes, whereas erythrocyte selenium was normal and did not change in any group. Nowadays, in the Grenoble area, the selenium status of cystic fibrosis patients is close to normal. Nevertheless, this study indicates a fragile equilibrium, given that selenium concentrations cn be lowered by placebo or mildly increased by supplementation.

Adolescent↗

PubMed1991

Parenteral supplementation with zinc in surgical patients corrects postoperative serum-zinc drop.

Zinc has been known for a long time to facilitate wound healing. But, so far, supplementation trials in patients treated by major severity surgery gave either partial or controversial results. In a double-blind, randomized study including 30 patients, we show that zinc supplements (30 mg/d for 3 d) administered by a drip correct postoperative drop of serum zinc, that this correction concerns the available part of serum zinc (i.e., zinc that is bound to compounds other than alpha-2 macroglobulin in serum), and that this supplementation can improve clinical wound healing. Possible influence of increased urinary output after the intervention is discussed, and we found that serum cortisol remains stable when zinc/albumin ratio is stable, and increases sharply when the same ratio drops. Cortisol, therefore, seems to play a major role in zinc redistribution after surgery.

Aorta, Abdominal↗

PubMed1991

[Hepatic metastasis of unknown primary site].

In this retrospective study, 91 patients (30%) out of a series of 304 with metastatic cancer of unknown primary site were found to have liver metastases. The liver was the only metastatic site in 28 (31%) cases and was associated with other sites in 63 (69%) cases. Median age was 62 yr in 61 male patients and 59 yr in 30 female patients. Thirty patients were submitted to an extensive investigation in search of the primary tumor, including systematic endoscopies: no primary cancer was found in these patients. In 61 other patients, only symptom-oriented investigations were performed and the primary cancer was found in 11 cases. The histologic type was adenocarcinoma in 71 (78%) cases, undifferentiated in 11 (12%) cases, epidermoid in 5 (6%) cases and determined by cytology alone in 4 cases. The median survival was 4 months in patients with metastases in the liver only, and 5 months in the other patients. This difference was not significant, so prognostic factors such as the Karnofsky index, weight loss, CEA and LDH levels were evaluated in the entire group; these factors do not have significant prognostic value. By contrast, when patients were able to receive chemotherapy, median survival was better (4 months) than without (median survival: 1 month; P = 0.005). In addition, in the case of objective response to chemotherapy, the median survival was 9 months versus 3.5 months for patients without objective response (P = 0.001). Seventy-three out of 91 patients (80%) were treated with chemotherapy regimen; 65 patients were evaluable: the objective response rate was 11 +/- 7% (7/65). Different regimens were used. With a non-toxic combination of fluorouracil, vinblastine and cyclophosphamide, 3 partial responses greater than or equal to 50% out of 43 patients (7 +/- 8%) were obtained. No significant advantage was observed when adriamycin was added to FU (4/13): 31 +/- 25%. Second- or third line chemotherapy regimen due to progression of the disease after the first-line combination provided only one objective response out of 36 patients. According to this retrospective study we recommend that overinvestigation be avoided in patients, with liver metastases of unknown primary site and that these patients be treated with non-toxic drug combinations.

Adenocarcinoma↗

PubMed1990

Is there an abnormal fasting duodenogastric reflux in nonulcer dyspepsia?

A quantitatively and/or qualitatively abnormal duodenogastric reflux (DGR) could be involved in the pathogenesis of nonulcer dyspepsia (NUD). The aims of this prospective study were to look for (1) a pathological DGR profile during fasting and (2) an eventual correlation between DGR profile and clinical symptoms. Twenty-six NUD patients were investigated. Seven other operated patients with a surgical procedure facilitating DGR episodes and 27 healthy volunteers served as control groups. A clinical score was determined for each patient from a standardized questionnaire. Gastric aspiration was performed for 6 hr in fasting subjects. The aspirates were pooled into 17 samples. In each sample the concentration and the output of total bile acids was determined. If the concentration was larger than 30 mumol/liter in pooled samples, the concentrations of free bile acids and the distribution of the conjugated bile acids was determined. The percentage of aliquots with a total bile acid concentration larger than 50 mumol/liter (without upper limit), and the percentage with a concentration larger than 2500 mumol/liter was also obtained. No significant difference was demonstrated between the healthy volunteers and NUD patients, whatever the parameter considered. However, there was a significant increase in each of the quantitative parameters for the group of operated patients in comparison with the NUD patient group. No significant correlation was found between the clinical score and the DGR profile in NUD patients. Apparently, DGR episodes do not play a primary role in the pathogenesis of NUD.

Adult↗

PubMed1990

Determination of the major zinc fractions in human serum by ultrafiltration.

In this paper we report a method for measuring ultrafiltrable zinc in human serum by electrothermal atomic absorption spectrophotometry. We show also that ultrafiltration permits to determine alpha-2-macroglobulin bound zinc and loosely bound zinc if a strong zinc ligand (EDTA) is added to serum before ultrafiltration. This last fraction, after deduction of ultrafiltrable zinc, represents roughly all albumin bound zinc. In 20 controls we found that ultrafiltrable zinc amounted 0.311 mumol/L (S.D. = 0.117 mumol/L), alpha-2 macroglobulin bound zinc 3.08 mumol/L (S.D. = 0.221 mumol/L), and albumin bound zinc 12.11 mumol/L (S.D. = 1.95 mumol/L). Our method needs only a small volume of serum, it is simple and rapid but also very accurate and reliable. The loosely bound fraction is very dynamic and, representing the physiologically active part of serum zinc, it could be a good marker of zinc deficiency.

Biomarkers↗