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Biomedical subjects

R Bourdon

Publications and source records attributed to R Bourdon.

At least 19 recordsLinked to original sources

High cardiac zinc levels in spontaneously hypertensive rats.

OBJECTIVES: Higher cardiac zinc levels have been observed previously in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats. However, this difference was established in adult males only and needed to be confirmed on a larger number of animals of both sexes. We also explored the respective roles of genetic and environmental factors in the genesis of this zinc anomaly as well as the causal relations with hypertension. DESIGN: Cardiac zinc levels were determined in adult male and female SHR and WKY rats originating from various colonies and submitted to various experimental conditions (anaesthesia, stress). These determinations were also performed in 3-week prehypertensive SHR and in adult Wistar rats submitted or not to deoxycorticosterone acetate-salt-induced hypertension. METHOD: Zinc levels were measured by flame atomic absorption spectrophotometry. RESULTS: In adults, cardiac zinc content was significantly higher in SHR than in WKY rats irrespective of sex and experimental conditions. In young prehypertensive rats, the difference between SHR and WKY cardiac zinc levels was also very significant. Experimental hypertension induced in Wistar rats did not entail any significant rise in cardiac zinc levels. CONCLUSIONS: These findings indicated that the higher cardiac zinc of SHR is not secondary to blood pressure elevation. High erythrocyte zinc, previously described in SHR, together with the present data suggest the occurrence of a primary genetic defect leading to high intracellular zinc in SHR. The possible role of this zinc anomaly in the development of hypertension and/or cardiac hyperplasia is discussed.

Aging

Diverse biological parameters in clinically healthy sheep from a flock with scrapie: variations, and correlations with OLA antigens.

A comparison was made in the blood levels of various cell types and biochemical substances and in lymphocyte antigens between 107 healthy sheep from a flock contaminated with scrapie (HC sheep) and 93 sheep from a noncontaminated flock (NC sheep), which served as a control population. Significant differences between the two groups of sheep were found in some of the levels, as had previously been found with lymphocyte antigens. The HC sheep, which included genetically resistant animals, could be distinguished from the NC sheep by their lower levels of various white cells, a noticeable decrease in urea, a moderate decrease in Mg2+ and Mn2+ ions, beta- and gamma-globulins, serotonin and vitamin B12, a strong increase in uric acid and a moderate increase in K+, Cl-, HCO3-, Zn2+, and Al3+ ions, as well as in total lipids and in the albumin to globulin ratio. In this HC population, the only enzyme with an increased level was aldolase; the levels of the other 7 enzymes measured were lowered. The observed modifications were considered to be signs of latent disturbances in the leukocyte system and in hepatic and renal functions, in spite of apparent resistance. Eleven lymphocyte antigens were studied. These antigens are not independent of the blood levels of the various substances measured, but are often correlated in a statistically significant manner with some of them. In the HC sheep, the lymphocyte antigens correlated with the modified levels in the blood were different from those in the control population.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Intraperitoneal chemotherapy for ovarian adenocarcinoma: pharmacokinetics of cisplatin].

Chemotherapy using cis dichlorodiamine platinum (CDDP) in doses of 30 and 60 mg/m2 was carried out in 6 patients who had adenocarcinoma of the ovary, that had not been treated before, 15 to 120 minutes before surgery was carried out. The results of doses of platin given on the blood levels are demonstrated. A slight and progressive increase in the plasma levels of CDDP with peaks between 0.6 and 1.95 of total platinum and 0.22 mcg/ml of free platin were found. The tissue levels in the region of the ovaries were found to be between 0.16 and 0.94 mcg/mg. There was a stepwise increase in the levels found in the pathological peritoneal cover of between 0.42 and 31.2 mcg/mg. This dropped as time went by; and then led to change in accordance with the intra-peritoneal concentrations. This study shows that it is possible when giving drugs intraperitoneally to avoid high plasma peaks and to obtain good levels of concentration of cisplatin in the peritoneum.

Adenocarcinoma

Elevated blood cyanide concentrations in victims of smoke inhalation.

BACKGROUND: The nature of the toxic gases that cause death from smoke inhalation is not known. In addition to carbon monoxide, hydrogen cyanide may be responsible, but its role is uncertain, because blood cyanide concentrations are often measured only long after exposure. METHODS: We measured cyanide concentrations in blood samples obtained at the scene of residential fires from 109 fire victims before they received any treatment. We compared the results with those in 114 persons with drug intoxication (40 subjects), carbon monoxide intoxication (29 subjects), or trauma (45 subjects). The metabolic effect of smoke inhalation was assessed by measuring plasma lactate at the time of admission to the hospital in 39 patients who did not have severe burns. RESULTS: The mean (+/-SD) blood cyanide concentrations in the 66 surviving fire victims (21.6 +/- 36.4 mumol per liter, P less than 0.001) and the 43 victims who died (116.4 +/- 89.6 mumol per liter, P less than 0.001) were significantly higher than those in the 114 control subjects (5.0 +/- 5.5 mumol per liter). Among the 43 victims who died, the blood cyanide concentrations were above 40 mumol per liter in 32 (74 percent), and above 100 mumol per liter in 20 of these (46 percent). There was a significant correlation between blood cyanide and carbon monoxide concentrations in the fire victims (P less than 0.001). Plasma lactate concentrations at the time of hospital admission correlated more closely with blood cyanide concentrations than with blood carbon monoxide concentrations. Plasma lactate concentrations above 10 mmol per liter were a sensitive indicator of cyanide intoxication, as defined by the presence of a blood cyanide concentration above 40 mumol per liter. CONCLUSIONS: Residential fires may cause cyanide poisoning. At the time of a patient's hospital admission, an elevated plasma lactate concentration is a useful indicator of cyanide toxicity in fire victims who do not have severe burns.

Adolescent

[Analytical exploration of drug addiction].

The natural and synthetic substances most frequently leading to drug addiction are described. They include cannabis, opium and cocaine with their respective derivatives. The authors insist on the problems encountered by analytical chemists when they examine urine samples containing these substances, owing to their metabolic degradation and to interferences between lawful and unlawful drugs. The limitations imposed by these problems to an unambiguous interpretation of the results obtained are defined, but they do not throw any doubt on the value of these investigations.

Chromatography, Gas

Hemodynamic effects of hydroxocobalamin in conscious dogs.

Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. However, its hemodynamic effects remain unknown. The authors therefore investigated the effects in chronically instrumented conscious dogs (n = 8) that were randomly given hydroxocobalamin (20, 70, and 140 mg.kg-1) or saline. Determination of peak cobalt plasma concentrations showed that 20 and 70 mg.kg-1 hydroxocobalamin correspond to "therapeutic doses," whereas 140 mg.kg-1 corresponds to a supratherapeutic dose. Hydroxocobalamin did not modify heart rate, mean arterial pressure, left ventricular (LV) end-diastolic pressure, and PR and QT intervals, regardless of the dose administered. The largest dose (140 mg.kg-1) induced a decrease in the maximum increase of LV pressure (-7 +/- 3%; P less than 0.05), maximum aortic blood flow acceleration (-17 +/- 5%; P less than 0.05), and cardiac output (-19 +/- 6%; P less than 0.05), whereas systemic resistance increased (+41 +/- 9%; P less than 0.05). In six other dogs, local administration of hydroxocobalamin (0.5, 1.5, and 5.0 mg.kg-1.min-1) confirmed that, in large doses, this drug has direct vasoconstrictor properties affecting both conductance (decrease in iliac artery diameter: -2.5 +/- 0.8%) and resistance (decrease in iliac artery blood flow: -19.5 +/- 3.4%) vessels. Thus, hydroxocobalamin should be a safe cyanide antidote, considering the lack of hemodynamic effects within the therapeutic range of doses.

Animals

Tissue and blood magnesium levels in spontaneously hypertensive rats, at rest and in stressful conditions.

Magnesium (Mg) levels were measured by flame atomic absorption spectrophotometry in the blood (plasma, erythrocytes) and soft tissues (liver, brain, heart, aorta, kidneys, adrenals, spleen, thymus) of adult spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY). In experiment 1, Mg determinations were performed on eight animals of each strain at rest. Mg levels were lower in brain (P less than or equal to 0.05), kidneys (P less than or equal to 2.10(-4] and erythrocytes P less than or equal to 0.01) in SHR than in WKY rats. Tissue water content was the same in the two strains. These results suggest the occurrence of lower intracellular Mg levels in SHR than in WKY. In experiment 2, 15 SHR and 15 WKY were submitted either to acute (1 d) or subacute (22 d) stresses or reared in restful conditions. Acute stress induced important Mg shifts leading to a decreased difference between SHR and WKY in most tissues and to an increased and more significant difference (P less than or equal to 0.01) in spleen and plasma Mg levels. Subacute stress was milder and had little effect. It is concluded that the results of experiment 1 cannot be attributed to the greater sensitivity of SHR to laboratory manipulations. When compared with previously published data our results nevertheless suggest an association between stress sensitivity and genetic factors regulating Mg metabolism.

Animals

[Ethical and analytical problems in man and greater mammals].

Toxicomania and doping give rise to an increasing number of drug measurements in the body fluids. Consequently the analysts have to face, at one and the same time, ethical and analytical problems. Should the analyst participate to investigations organised in order to disclose a toxicomania in a working place? The author suggests a positive answer as long as the adduct person benefits to a social and medical care. What is the analytical meaning of a positive test? Taking into account the increasing sensitivity of the methods used, thresholds have to be established, at least for the blood concentrations of the licit drugs, in order to avoid asserving the legality to the sensitivity of the apparatus.

Animals

Effect of acute ethanol administration on the subcellular distribution of iron in rat liver and cerebellum.

An acute ethanol load (50 mmol/kg, i.p.) produced altogether a decrease in the non-heme iron content of the serum and an increase in the iron content in liver and cerebellum. Subcellular fractionation studies indicated that the non-heme iron accumulated by the liver, 4 hr after the ethanol load, was recovered in light mitochondria, microsomes and cytosol, and that iron accumulated by the cerebellum was localized in heavy mitochondria, light mitochondria, microsomes and cytosol. The low molecular weight chelatable (LMWC) iron content as well as the percentage of total non-heme iron represented by LMWC-iron were increased in the cytosol of liver and cerebellum after the ethanol load. These results suggest that an acute ethanol load induces (i) a shift in the distribution between circulating and tissular non-heme iron; (ii) an increase in the cytosolic LMWC-iron which, by favouring the biosynthesis of reactive free radicals, may contribute to lipid peroxidation in liver and cerebellum.

Animals

Sensitive radioimmunoassay and enzyme-linked immunosorbent assay for the simultaneous determination of chloroquine and its metabolites in biological fluids.

Two new methods for the simultaneous determination of chloroquine and its two main metabolites (monodesethylchloroquine and bisdesethylchloroquine) in biological samples, radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), are described. Antiserum is produced in rabbits immunized with N-(2-carboxyethyl)desethylchloroquine:protein conjugate. Besides chloroquine, this antiserum recognizes with good affinity the two main metabolites, monodesethylchloroquine and bisdesethylchloroquine (70 and 40% of crossreaction, respectively). Amodiaquine cross reacts by 4.5%; cross reactions with monodesethylamodiaquine, bisdesethylamodiaquine, and other antimalarial drugs are less than 1%. No extraction step or sample preparation is required for either system. Sensitivity limits are, respectively, 0.70 nM (3 pg of chloroquine sulfate measured in 10 microL of plasma sample) for RIA, and 10 nM (22 pg of chloroquine sulfate measured in 5 microL of plasma sample) for ELISA. The interassay coefficients of variation are, respectively, less than 10 and less than 16% for RIA and ELISA in the range 14-410 nM (6-180 ng/mL). The results of both methods are well correlated (r = 0.97) and correlate with spectrophotometry (r = 0.98) and HPLC results (r = 0.93). Because of their high sensitivity, both methods can be used in the case of chloroquine poisoning and in the control of malaria prophylaxis and treatment.

Animals

Blood and tissue zinc levels in spontaneously hypertensive rats.

Zinc (Zn) determinations were performed on blood plasma and red cells, liver, heart, adrenals, and spleen of spontaneously hypertensive (SHR) and control normotensive (WKY) male rats, 20 weeks of age. SHR revealed higher red cell (p = 2 x 10(-5)) and heart (p = 0.007) Zn levels than WKY rats. The water content of organs was the same in the two strains. When compared with published data, these results suggest an association between high cell Zn levels and hypertension, the meaning of which is briefly discussed.

Adrenal Glands

Aluminium intoxication in the rat induces partial resistance to the effect of recombinant human erythropoietin.

Anaemia is a major complication of chronic renal failure. It is mainly due to a decrease in the production of erythropoietin and at present it can be corrected by recombinant human erythropoietin (rHuEpo). The question has arisen whether aluminium overload, which is frequently observed in uraemic patients, could exert a resistance to the effect of rHuEpo. To answer this question, we submitted two series of rats with two groups in each to an experimental aluminium intoxication. Group II rats received repeated i.p. injections of aluminium, whereas group I (control) rats were given vehicle solution alone. Subsequently, all rats were treated with identical s.c. doses of rHuEpo (100 IU/kg body-weight twice weekly). In the first series, rats were fed ad libitum whereas in the second, rats were pair-fed and received iron supplementation. In the first series, group I rats had an increase of mean haemoglobin in response to rHuEpo: 15.6 +/- 0.3 vs 19.8 +/- 0.3 g/dl, P less than 0.001. In contrast, group II rats had a decrease: 15.1 +/- 0.2 vs 10.1 +/- 0.8 g/dl, P less than 0.001. However, compared to group I rats, group II rats did not gain body-weight and their plasma iron concentration was less. In the second series, mean haemoglobin concentration of group I rats increased from 15.1 +/- 0.2 to 18.9 +/- 0.3 g/dl (P less than 0.001) in response to rHuEpo.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum

Effect of abstinence from alcohol on the depression of glutathione peroxidase activity and selenium and vitamin E levels in chronic alcoholic patients.

Glutathione peroxidase activity and selenium and vitamin E levels were measured in the plasma and erythrocytes of 25 chronic alcoholic patients without liver cirrhosis before and after 14 days of abstinence from alcohol, and compared with the levels in 25 sex- and age-matched healthy controls. Before abstinence, all three levels were shown significantly depressed in the alcoholic patients compared with the controls, in both plasma (80, 71, and 89% of control values) and erythrocytes (68, 70, and 83% of control values). After a 14-day abstinence period with no dietary supplementation, a trend towards normalization was noted in erythrocyte (vitamin E and glutathione peroxidase 74 and 91% of control values respectively), in whole blood selenium (82%) and plasma in vitamin E (74%). However, plasma selenium and glutathione peroxidase values were lower than pre-abstinence values (76% and 86% of control values respectively). Our results point to a deficiency in the antioxidant defense system of chronic alcoholics before the occurrence of severe liver disease. This lack of protection against lipoperoxides is all the more important in circumstances like chronic alcohol consumption, in which lipid peroxidation is known to increase. However, the present study also demonstrated that during 14 days of a normal diet free of ethanol, a rapid trend occurred towards the normalization of the factors.

Adult

Toxicokinetics of paraquat in humans.

1. The toxicokinetics of paraquat were studied in 18 cases of acute human poisoning using a specific radioimmunoassay. Plasma paraquat concentration exhibited a mean distribution half-life (t1/2 alpha) of 5 h and a mean elimination half-life (t1/2 beta) of 84 h. Cardiovascular collapse supervened early during the course of the intoxication and was associated with the distribution phase. Death related to pulmonary fibrosis occurred late and was associated with the elimination phase. 2. Pharmacokinetic analysis of urine paraquat excretion confirmed the biphasic decline of paraquat. Moreover, renal paraquat and creatinine clearances were not correlated but renal paraquat clearance was never higher than the renal creatinine clearance. 3. Tissue paraquat distribution was ubiquitous with an apparent volume of distribution ranging from 1.2 to 1.6 l/kg. Muscle could represent an important reservoir explaining the long persistence of paraquat in plasma and urine for several weeks or months after poisoning.

Adult

Studies of variations of subcutaneously infused desferrioxamine and iron movements in thalassaemia children.

Desferrioxamine (DFO) plus ferrioxamine (FO) variations and alterations in plasma and urinary iron (Fe) levels were investigated in eight children with thalassaemia major during a 12-h s.c. DFO infusion at a dose of 40 mg/kg body weight. During the infusion, blood samples were regularly taken and total urine was also regularly collected in all patients. In the plasma, a mean DFO plus FO plateau level of 9 mg/l was reached after 4 h and remained steady in the subsequent 8 h. At 30 h the mean DFO plus FO concentration in plasma was still 4.5 mg/l. At 30 h, the urinary excretion ranged from 15% to 70% of the infused dose (mean: 42%). In plasma, the Fe concentration increased on average by 20% (range 10%-30%), remained steady during the DFO infusion, then returned to the basal level after 16-24 h. Urinary Fe excretion started early and still persisted 18 h after the infusion. The amount excreted at 30 h ranged from 5 to 27 mg (mean: 13.6 mg). This study emphasizes the delay in obtaining a DFO plus FO plateau in plasma, the important interindividual variations and the slow decrease of the drug after the end of the infusion. It points out the delay and the values of the urinary Fe excretion compared to the plasmatic and urinary drug variations.

Adolescent

Short-term effects of parathyroidectomy on plasma biochemistry in chronic uremia.

Parathyroidectomy (PTx) is indicated in hemodialysis (HD) patients who have severe osteitis fibrosa unresponsive to vitamin D therapy or in whom the latter treatment is contraindicated. Immediately after PTx, plasma immunoreactive parathyroid hormone, calcium and phosphorus concentrations decline abruptly. However, little is known in such patients about the short-term effects of PTx on plasma alkaline phosphatase (AP) activity and plasma aluminum (Al) levels. The present, preliminary study was performed to determine such parameters in 37 HD patients, and to correlate them with data of bone histology. Mean plasma AP activity started to increase after PTx from day 4 onwards. Thus, AP values significantly higher than pre-PTx values were observed at day 7 and 14 (415 +/- 54 vs. 619 +/- 77 and 749 +/- 83 IU/liter, means +/- SEM; N = 37; P less than 0.05 and 0.001, respectively). This increase, in the absence of changes in liver function, was mainly due to the bone-specific iso-AP. Moreover, the degree of increase in plasma AP activity was higher in the subgroup with negative (group I, 21 patients) than in that with positive bone Al staining (group II, 16 patients). However, plasma osteocalcin (BGP) did not change after PTx (N = 8). Basal plasma Al levels were significantly higher in group II both before and two weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase

[Iron deficiency and Pseudomonas aeruginosa colonization in cystic fibrosis].

The incidence of iron deficiency and its relationship with the concentration or iron in sputum and the number of Pseudomonas aeruginosa (PA) colonies was studied in an unselected group of 53 cystic fibrosis (CF) patients with an age range of 3 months to 21 years. Parameters used to assess the iron status included serum iron, the % saturation of transferrin (n = 53). The number of subjects with depletion of iron stores was estimated by levels of ferritin (n = 50). The concentration of iron and of PA was measured in a subgroup (n = 24) and compared to a control group (n = 8) with pulmonary infections of varying etiology. A close correlation was found between serum iron and the % saturation of transferrin (r = 0.952; p less than 0.001). Between 22.6 to 28.3% of patients were found to be iron deficient. An abnormally low ferritin (less than 12 ng/ml) was noted in 28% of cases but no correlation could be established between changes of serum iron and ferritin levels as a function of the degree of infection and/or of inflammation. In 62% of cases (n = 15) the concentration of iron in sputum was found to be within the range of control values (12-27 mumols/l). In 38% of cases (n = 9), ferritin values were above 27 mumols/l. No correlation was found between the concentration of iron and the number of PA colonies in sputum. We can therefore conclude the following: 1) iron deficiency is more common in CF than previously reported; 2) ferritin levels constitute a poor index of iron deficiency; 3) colonisation with PA is not associated with iron content of bronchial secretions.

Adolescent

[Spectrometry emission by inductively coupled plasma (SEPIHF). Application in the determination of inorganic compounds].

The authors describe the principle of inductively coupled argon plasma emission spectrometry (ICP) to determine inorganic compounds in biological samples. This method is compared with more classical electrothermal flame atomisation absorption spectrometry. The association of ICP with different instruments is reminded (HPLC, mass spectrometry, graphite furnace, hybride generation). Finally, the review ends with some applications in biological fluids.

Aluminum