Search PubMed⌕ Search

Biomedical subjects

E Fontaine

Publications and source records attributed to E Fontaine.

At least 73 records · Page 4Linked to original sources

Uncoupling effect of polyunsaturated fatty acid deficiency in isolated rat hepatocytes:effect on glycerol metabolism.

The effects of a 4-week deficiency in polyunsaturated fatty acids (PUFA) in isolated rat hepatocytes have been investigated for oxidative phosphorylation and fatty acid, dihydroxyacetone (DHA) or glycerol metabolism. Oxygen uptake was significantly increased (by 20%) with or without fatty acid addition (octanoate or oleate) in the PUFA-deficient group compared with controls. The effect persisted after oligomycin addition but not after that of potassium cyanide, leading to the conclusion that, in these intact cells, the mitochondria were uncoupled. The PUFA-deficient group exhibited a significant decrease in the cytosolic ATP/ADP ratio, whereas the mitochondrial ratio was not affected. PUFA deficiency led to a 16% decrease in DHA metabolism owing to a 34% decrease in glycerol kinase activity; the significant decrease in the ATP/ADP ratio was accompanied by an increase in the fractional glycolytic flux. In contrast, glycerol metabolism was significantly enhanced in the PUFA-deficient group. The role of the glycerol 3-phosphate dehydrogenase step in this stimulation was evidenced in hepatocytes perifused with glycerol and octanoate in the presence of increased concentrations of 2,4-dinitrophenol (Dnp): uncoupling with Dnp led to an enhancement of glycerol metabolism, as found in PUFA deficiency, although it was more pronounced than in controls. The matrix/cytosol gradients for redox potential and ATP/ADP ratio were lower in cells from PUFA-deficient rats, suggesting a decreased mitochondrial membrane potential in accordance with the uncoupling effect. Moreover, a doubling of the mitochondrial glycerol 3-phosphate dehydrogenase activity in the PUFA-deficient group compared with controls led us to conclude that the activation of glycerol metabolism is the consequence of two mitochondrial effects: uncoupling and an increase in glycerol 3-phosphate dehydrogenase activity.

Adenosine Diphosphate↗

Reappraisal of endoscopic sphincterotomy for post-traumatic neurogenic bladder: a prospective study.

PURPOSE: We assessed the results of endoscopic sphincterotomy in patients with detrusor-sphincter dyssynergia secondary to spinal cord injury. MATERIALS AND METHODS: A prospective study was done of 92 patients with a mean followup of 20.6 months. RESULTS: The morbidity rate was 10.9%. Results demonstrated objective (assessed by the decrease in voiding pressure) and subjective (expressed by the patient) improvement in quality of micturition in 83.7% and 73% of the cases, respectively. Subjective autonomic dysreflexia resolved in 93.2% of the cases. CONCLUSIONS: Sphincterotomy is a useful and effective therapeutic method for neurogenic bladder when all available pharmacological treatments and clean intermittent catheterization have failed.

Adult↗

[Augmentation ileocystoplasty in neurologic bladder].

OBJECTIVE: The authors evaluated the results of augmentation ileocystoplasty in patients presenting with neurogenic urinary incontinence. MATERIALS AND METHODS: A prospective study was conducted in 36 patients (25 women, 11 men) 30 of whom simultaneously underwent a bladder neck continence procedure. The mean follow-up was 32.2 months. RESULTS: Daytime continence was obtained in 32 patients (88.8%). Thirty patients (83.3%) were continent a night. The upper urinary tract did not deteriorate. One patient developed bladder stones and 2 presented a vesical perforation. Urodynamic studies showed an increased functional bladder capacity and compliance (p < 0.001) and loss of uninhibited bladder contractions. CONCLUSION: Augmentation ileocystoplasty is an effective and reliable surgical procedure after failure of conservative management. However, long-term complications can occur and regular surveillance is necessary.

Adolescent↗

Octanoate affects 2,4-dinitrophenol uncoupling in intact isolated rat hepatocytes.

When intact isolated rat hepatocytes, either incubated or perifused, were uncoupled by 2,4-dinitrophenol, we found that the effect on glucose and lactate+pyruvate fluxes, cytosolic and mitochondrial redox states and ATP/ADP ratios were dependent on the nature of the exogenous substrate added. 2,4-Dinitrophenol addition (0.25 mmol/l) to cells perifused with dihydroxyacetone (10 mmol/l) resulted in a modest and transient activation of oxygen uptake accompanied by a surprising rise in lactate/pyruvate ratio indicating an increase in the cytosolic NADH/NAD+ ratio. In addition, such uncoupling, fully abolished glucose production, enhanced lactate+pyruvate flux, and strongly decreased cytosolic and mitochondrial ATP/ADP ratios. In these steady-state conditions, further addition of octanoate (0.4 mmol/l) induced a large and sustained enhancement of respiration with a concomitant decrease in the lactate/pyruvate ratio, whereas glucose flux was restored to some extent and cytosolic and mitochondrial ATP/ADP ratios increased. Inhibition of the malate-aspartate shuttle by the transaminase inhibitor aminooxyacetate (0.3 mmol/l) did not modify the effect of 2,4-dinitrophenol with dihydroxyacetone alone whereas it decreased the maximal stimulation of oxygen uptake after octanoate addition. In view of these results we propose the following conclusions. The uncoupling of intact cells by 2,4-dinitrophenol inhibits the translocation of reducing equivalents into the mitochondrial matrix probably by impairing the malate-aspartate shuttle. This explains the increase in the cytosolic NADH/NAD+ ratio and the transient activation of respiration with dihydroxyacetone. Fatty acid addition to cells uncoupled with 2,4-dinitrophenol appears to restore a mitochondrial membrane potential, probably by providing the respiratory chain with reduced cofactors directly in the matrix, thus allowing the transfer of reducing equivalents across the mitochondrial membrane. The restoration, to some extent, of a protonmotive force to uncoupled cells by fatty acid addition is also supported by an increase in ATP synthesis as evidenced by a glucose synthesis with dihydroxyacetone as gluconeogenic substrate.

2,4-Dinitrophenol↗

Correlation between degree of rupture of outer mitochondrial membrane and changes of kinetics of regulation of respiration by ADP in permeabilized heart and liver cells.

Kinetics of regulation of respiration by ADP in skinned cardiac fibers and permeabilized isolated hepatocytes was compared before and after mitochondrial swelling due to hypoosmotic treatment in 30-50 mOsM solutions. In both systems the apparent Km for ADP was high before mitochondrial swelling and equal to 297 +/- 35 microM and 275 +/- 35 microM, correspondingly. Hypoosmotic treatment resulted in the rupture of outer mitochondrial membrane and in the loss of exogenous cytochrome c, and both in skinned cardiac fibers and permeabilized hepatocytes the value of apparent Km for ADP was decreased in correlation with the extent of the rupture of the outer mitochondrial membrane. It is concluded that both in heart and liver cells in vivo, the ADP diffusion in the cells is retarded due to very low permeability of the outer mitochondrial membrane for ADP.

Adenosine Diphosphate↗

Isolated rat hepatocyte metabolism is affected by chronic renal failure.

Metabolic changes due to chronic renal failure (CRF) were studied in isolated liver cells. In 14 CRF and 14 sham-operated rats, liver cells were isolated by the Berry and Friend method and incubated with various substrates in order to study gluconeogenesis, ureagenesis, ketogenesis, oxygen consumption as well as cytosolic and mitochondrial adenine nucleotide content. CRF rat hepatocytes exhibited a 25% to 45% decrease in gluconeogenesis and ureagenesis (P < 0.05) from all the tested substrates (lactate plus pyruvate, fructose, glycerol, dihydroxyacetone, alanine and glutamine for gluconeogenesis and alanine, glutamine, ammonia and ammonia plus ornithine for ureagenesis), while endogenous rates were unaffected. CRF did not alter ketone body production (acetoacetate and beta-hydroxybutyrate) from oleate or octanoate. In the presence of either oleate, lactate plus pyruvate or ammonia, oxygen uptake as well as cytosolic and mitochondrial total adenine nucleotides were unaffected by CRF, while the mitochondrial ATP/ADP ratio decreased (P < 0.001). Thus, this study of hepatocyte intermediary metabolism during CRF showed an alteration of only gluconeogenesis and ureagenesis pathways. Moreover, the association of normal oxygen uptake together with decreased mitochondrial ATP/ADP ratio suggest a possible increase in hepatocyte ATP demand during uremia.

Adenine Nucleotides↗

Mechanism of gluconeogenesis inhibition in rat hepatocytes isolated after in vivo hypoxia.

Gluconeogenesis was studied in hepatocytes isolated from fasted rats submitted to 24 h of hypoxic exposure (inspired O2 fraction 0.1) or to room air. Hepatocytes from hypoxic rats compared with controls exhibited a lower gluconeogenic rate with lactate (5.1 +/- 0.3 vs. 7.2 +/- 0.3 mumol.min-1.g dry cells-1, P < 0.001) but not with dihydroxyacetone (9.1 +/- 0.3 vs. 9.4 +/- 0.4 mumol.min-1.g dry cells-1), suggesting involvement of the phosphoenolpyruvate-pyruvate cycle. Experiments with perifused hepatocytes from hypoxic and control rats showed a single relationship between phosphoenolpyruvate and glucose flux (JGlc) but two different curves when cytosolic oxalacetate was plotted against JGlc. The decreased phosphoenolpyruvate carboxykinase (PEPCK) activity in the hypoxic group (9.0 +/- 0.9 vs. 16.2 +/- 1.9 nmol.min-1.mg protein-1, P < 001) without change in the Michaelis constant further settled the involvement of this step. The significant decrease in PEPCK mRNA levels in livers from hypoxic rats led us to propose that in vivo hypoxic exposure inhibits gluconeogenesis at the PEPCK level by decreasing PEPCK gene transcription.

Adenine Nucleotides↗

Decrease in cytosolic ATP/ADP ratio and activation of pyruvate kinase after in vitro addition of almitrine in hepatocytes isolated from fasted rats.

Previously, we have shown in experiments with isolated mitochondria that almitrine, a drug used for patients with chronic lung disease, affects the H+/ATP stoichiometry of the F0F1-ATPase [Rigoulet, M., Fraisse, L., Ouhabi, R., Guérin, B., Fontaine, E. & Leverve, X. M. (1990) Biochim. Biophys. Acta 1018, 91-97]. In the present study, we have investigated the effect of almitrine on gluconeogenesis and oxygen consumption in isolated hepatocytes. Almitrine decreased both the cytosolic and mitochondrial ATP/ADP ratios but had no effect on oxygen consumption in cells incubated with and without octanoate. This must have been due to a double effect. On the one hand, a decrease in the ATP/ADP ratio decreases ATP utilization; on the other hand, in the presence of almitrine more oxygen is required to synthesize ATP. Almitrine did affect gluconeogenesis from various substrates (lactate + pyruvate, glycerone or fructose), but had no effect on glycerol or glutamine metabolism. The effect on gluconeogenesis from glycerone was due to an increase in glycolytic flux. The rate of lactate + pyruvate production increased whereas there was no effect on glycerone utilization. This effect was caused by an activation of pyruvate kinase. Our data indicate that this enzyme is an extremely sensitive sensor of the cytosolic ATP/ADP ratio. Hence, under our experimental conditions, the cytosolic ATP/ADP ratio decrease affects only the balance between glucose and lactate + pyruvate productions, and not the phosphorylation of glycerone, the first and controlling step of this pathway.

Adenosine Diphosphate↗

[A modified cervico-prostatic incision technic in hypertrophic adenoma in young subjects desiring to preserve ejaculation].

The treatment of bladder neck obstruction by transurethral resection of the prostate is responsible for retrograde ejaculation, which is poorly tolerated by our younger patients. Bladder neck incision, initially proposed as treatment for bladder neck sclerosis and for small prostates, was performed according to a modified technique in 36 patients with a mean age of 57.6 years (range: 41-72 years), with benign prostatic hypertrophy less than 30 grams and wishing to retain antegrade ejaculation. This technique consists of creating a deep groove with the resector hook extending from the ureteric orifice to 5 mm above the verumontanum, incising the full thickness of the detrusor and prostatic urethra as far as the retrocervical fat. This preserves a supramontanal ring of urethral muscle whose contraction during orgasm prevents retrograde ejaculation of semen. Resection of the median lobe was also performed in 8 patients, while sparing the cervical muscular ring. The mean follow-up was 2.4 years (range: 4-84 months). Dysuria was very considerably improved in 32 patients (91.5%), with a Madsen score of less than 2. Antegrade ejaculation was preserved in 32 patients (91.5%). Two patients had to undergo secondary prostatic resection because of persistent dysuria (these 2 patients retained antegrade ejaculation). Unilateral bladder neck incision, sparing a supramontanal muscular ring is an easy, rapid technique with low morbidity, effective in the treatment of prostatism due to a small prostate (less than 30 grams). It is the operation of choice in young patients with small prostates who wish to retain antegrade ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A review of 72 renal artery stenoses in a series of 715 kidney transplantations in children].

In a series of 715 renal transplantations performed between 1973 and 1989, 72 cases of renal artery stenosis (RAS) in 69 children (9.7%) were managed at Hôpital Necker Enfants Malades. Forty cases of RAS were treated exclusively by antihypertensive drugs. A good result was obtained in 82.5% of cases. Thirty three transluminal angioplasties (TLA) were performed in 23 children with 26 RAS. A good clinical result was obtained in 15 children with a total of 17 stenoses, corresponding to a success rate of 65%. Transluminal dilatation of anastomotic stenoses always failed. There were no cases of transplant thrombosis. Eleven RAS were operated, including 5 after failure of TLA. Eight patients (73%) obtained a clinical improvement. There were 2 postoperative thromboses. Antihypertensive treatment must be administered in every case. If medical treatment fails, and with the exception of anastomotic stenoses, TLA should be the first-line procedure, while surgery is reserved for failures of TLA and for anastomotic stenoses.

Adolescent↗

[Antenatal diagnosis of obstructive uropathies: state of the art].

The development of ultrasonography has allowed the antenatal diagnosis of various forms of obstructive uropathy. The diagnosis of urinary tract dilatation is now possible by the 15th week of pregnancy. More recently, the study of foetal urine biochemistry has defined the prognostic factors of the course of postnatal renal function. The authors define and limit the current indications for the various antenatal interventions on the basis of the combination of antenatal ultrasonography and foetal urine biochemistry.

Dilatation, Pathologic↗

[Characteristic aspects of vascular complications in renal transplantation in children].

In a series of 859 transplantations performed in children and adolescents from January 1973 to December 1992, vascular thrombosis accounted for 18% of all graft losses (2nd cause of graft failure), and 57% of early failures (within 2 months). Renal veins and arteries were equally affected. The young age of the donors and recipients constituted the main risk factor, thrombosis accounting for 40 and 37% respectively of all graft losses in donors and recipients < 5 years old. This explained the lower survival rate of these age groups after grafting, as reported in most published pediatric series. The prophylactic use of a low molecular weight heparin in high-risk grafts may help to decrease its incidence. A renal artery stenosis, located a few cm beyond the anastomosis in 2/3 of cases, was observed in 10% of grafts. Often severe hypertension (HBP) with cerebral complications, responsible for permanent sequelae in some cases, was the prominent symptom. Anti-hypertensive drug therapy was sufficient to control HBP in 40 cases out of 72, and in 10 of these, a spontaneous regression of the stenosis was remarked within a few months after repeated angiography. Transluminal angioplasty was used on 26 stenosis and was effective in 2/3 of cases; the recurrence rate, however, was 27%.

Adolescent↗

[Urethro-cervico-cystopexy using aponeurotic colposuspension: an original technic in the treatment of stress urinary incontinence. Apropos of 32 long-term reviewed cases].

This is an original technique for the treatment of isolated urinary stress incontinence without associated cystocele, designed to obtain a good result, stable in the long term, which avoids dysuria and phenomena of bladder irritation (frequency, urgency) inherent to suspension cervicopexy. It consists of a Gobell-Stoeckel operation, modified at two points: retrocervical dissection exclusively via a retropubic incision and fixation of a band of aponeurosis to the vagina before fixing it to Cooper's ligament to prevent compression of the posterior lip of the bladder neck. Thirty two patients with a mean age of 56 years (range: 41-83 years) were operated by this technique between 1986 and 1991. Sixteen of the 32 patients (50%) had a history of previous pelvic surgery: 14 hysterectomies, 4 cures of urinary stress incontinence, 4 cures of cystocele. Stress incontinence was associated with urgency in 25% of cases. Five patients developed 7 minor early complications: 3 benign parietal complications, 4 cases of transient urinary retention. The mean duration of indwelling catheterisation was 4 days (range: 2-6 days) and the mean length of hospital stay was 8 days (range: 6-20 days). The mean follow-up was 32 months (range: 12-70 months). Perfect continence was achieved in 91% of cases. 69% of patients obtained an excellent result (normal continence, no dysuria, no urgency), 19% obtained a moderate result (normal continence, but slight dysuria and/or urgency) and 12% obtained a poor result (2 cases of urge incontinence, 1 case of late incontinence secondary to a neurological lesion and 1 case of permanent incomplete retention requiring endoscopic section of the strip of aponeurosis). On the basis of these good long-term results, the authors propose this technique for the treatment of urinary stress incontinence in postmenopausal and/or previously operated women.

Adult↗

[Cutaneous trans-jejunal ureterostomy: an original technique used in 29 patients].

The authors report an original technique of transintestinal cutaneous diversion using the jejunum A 10 to 15 cm segment of jejunum is raised from the second loop and is attached to the skin transperitoneally. The stoma lies below the ureterojejunal anastomosis and the two ureters, sutured according to Wallace's technique, are implanted end-to-end into the proximal and extraperitonealised end at the height of the sacral promontory. 29 patients have been treated by this technique for various indications: 21 bladder tumors, 5 neurogenic bladders, 1 bladder exstrophy, 1 cervical cancer, 1 prostatic cancer. 15 patients (52%) had previously received pelvic irradiation. The mean follow-up was 47 months (2-192 months) and the mortality was zero. 4 patients (13.8% developed early complications: 2 cases of urinary tract obstruction and 2 intestinal obstructions requiring 3 operations. 6 patients developed 7 minor late complications (24.1%): 2 cases of pyelonephritis, 4 cases of renal stones, only one of which required an operation, and 1 case of prolapsed stoma. None of the patients developed any alteration in renal function or dilatation of the upper urinary tract after the operation. The addition of sodium bicarbonate was found to be useless, as none of the patients developed any metabolic disorders. Transjejunal cutaneous ureterostomy achieves excellent drainage by means of a short graft with a stoma situated below the level of the ureteric implantation, as reflected by the absence of any long-term deterioration in renal function despite full lumen ureterojejunal implantation without an antireflux device. This technique is simple to perform and is indicated in all situations, particularly after pelvic irradiation. It is associated with low morbidity, no mortality and ensures an excellent long-term result.

Adolescent↗

Flux-dependent increase in the stoichiometry of charge translocation by mitochondrial ATPase/ATP synthase induced by almitrine.

After studying the effects of almitrine, a new kind of ATPase/ATP synthase inhibitor, on two kinds of isolated mammalian mitochondrion, we have observed that: (1) Almitrine inhibits oligomycin-sensitive ATPase; it decreases the ATP/O value of oxidative phosphorylations without any change in the magnitude of delta mu H+. (2) Almitrine increases the mechanistic H+/ATP stoichiometry of ATPase as shown by measuring either (i) the extent of potassium acetate and of potassium phosphate accumulation sustained by ATP utilisation, or (ii) the electrical charge/ATP (K+/ATP) ratio at steady-state of ATPase activity. (3) Rat liver mitochondria are at least 10-times more sensitive to almitrine than beef heart mitochondria. (4) The change in H+/ATP stoichiometry induced by almitrine depends on the magnitude of the flux through ATPase. The inhibitory effect of almitrine on ATPase/ATP synthase complex, as a consequence of such an H+/ATP stoichiometry change, is discussed.

Acetates↗