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M Debray

Publications and source records attributed to M Debray.

At least 19 recordsLinked to original sources
PubMed2006

Age-dependent effects on redox status, oxidative stress, mitochondrial activity and toxicity induced by fluoroquinolones on primary cultures of rabbit tendon cells.

The age-related difference in fluoroquinolone-induced tendon toxicity was investigated. In vitro tendon cells from juvenile and young adult rabbits, respectively, were incubated with quinolone (nalidixic acid, NA) or fluoroquinolone (ofloxacin, OFX or pefloxacin, PEF) at 0.01 microM to 1 mM for 72 h. Redox status, glutathione (GSH), reactive oxygen species (ROS), and mitochondrial activity were assessed using intracellular fluorescent probes. Fluorescence signal was detected on living adherent tenocytes in microplates using cold-light cytofluorometry. Tendon toxicity differed significantly between the two cell groups and the difference was greatest with highest dose (1 mM). For 72 h, significant (p < 0.001) differences between immature and young adult primary tenocytes were observed for redox status decrease, GSH decrease, and ROS production increase. Mitochondrial activity remained unaltered in immature tenocytes. We confirm two groups of intrinsic tendon toxicity (OFX/NA vs. PEF) associated to oxidative stress (GSH decrease). Our in vitro experimental model confirms the clinical observations of age dependent tenotoxicity. First group (NA, OFX) showed greater intrinsic tenotoxicity for young adult than immature tenocytes, second group (PEF) was highly toxic for immature and young adult cells. The three quinolones do not altered mitochondrial activity in immature tenocytes whereas alteration was observed in young adult tenocytes.

Achilles Tendon↗
PubMed2005

Puromycin-based purification of rat brain capillary endothelial cell cultures. Effect on the expression of blood-brain barrier-specific properties.

One of the main difficulties with primary rat brain endothelial cell (RBEC) cultures is obtaining pure cultures. The variation in purity limits the achievement of in vitro models of the rat blood-brain barrier. As P-glycoprotein expression is known to be much higher in RBECs than in any contaminating cells, we have tested the effect of five P-glycoprotein substrates (vincristine, vinblastine, colchicine, puromycin and doxorubicin) on RBEC cultures, assuming that RBECs would resist the treatment with these toxic compounds whereas contaminating cells would not. Treatment with either 4 microg/mL puromycin for the first 2 days of culture or 3 microg/mL puromycin for the first 3 days showed the best results without causing toxicity to the cells. Transendothelial electrical resistance was significantly increased in cell monolayers treated with puromycin compared with untreated cell monolayers. When cocultured with astrocytes in the presence of cAMP, the puromycin-treated RBEC monolayer showed a highly reduced permeability to sodium fluorescein (down to 0.75 x 10(-6) cm/s) and a high electrical resistance (up to 500 Omega x cm(2)). In conclusion, this method of RBEC purification will allow the production of in vitro models of the rat blood-brain barrier for cellular and molecular biology studies as well as pharmacological investigations.

Animals↗
PubMed2003

[Excess antivitamin K in elderly hospitalised patients aged over 70. A one-year prospective survey].

INTRODUCTION: Antivitamin K treatments (AVK) are related to increased morbidity and mortality, notably in elderly patients. The International Normalized Ratio (INR) should be well controlled and its stabilisation within the therapeutic range help to prevent the haemorrhagic complications. METHODS: A one-year prospective survey on all the cases of excess AVK was conducted in hospitalised patients aged over 70. RESULTS: During the study period, 225 hospitalised patients treated with AVK (mean age 84 years) were identified: 62% received warfarin, 19% fluindione, 8% acenocoumarol and 11% received several successive AVK. During this period, 1.904 INR measurements were recorded: 97 (5.1%) were > or =5.0 and 12 (0.63%) were > or =9.0. In all, 59 patients (23.1%) exhibited one or several episodes of excess AVK (INR > or =5.0) and 57 exhibited a target INR of 2.5. Three patients died of accidental haemorrhage--two of them due to intra-cerebral bleeding--among the 59 patients with excess AVK. In three cases, the INR was greater than 7.0 at the time of the accident. DISCUSSION: In half of the cases of excess, the episode occurred during the month following initiation of treatment with AVK. In nearly two thirds of cases, a change had been made in drug therapy in the 10 days preceding the excess, with the prescription of a drug enhancing the effect of the AVK: anti-infection agents (antibiotics and anti-fungals) and amiodarone were the drugs most frequently involved. Oral or intravenous vitamin K1 was administered in only 19% of cases. CONCLUSION: In very old patients treated with oral anticoagulants, certain risk factors must be identified: the initiation period of treatment, the occurrence of an intercurrent disease and the subsequent change in the drug therapy. INR monitoring should be intensified in order to detect any excess and, if detected, ensure the optimal management of the patient.

4-Hydroxycoumarins↗
PubMed2003

Effect of age and photoperiodic conditions on metabolism and oxidative stress related markers at different circadian stages in rat liver and kidney.

It has been shown that some cytochrome P450-dependent enzyme activities could present daily fluctuations, particularly CYP3A isoenzymes which are enhanced during the dark period. The aim of this study was to investigate whether age and photoperiodic conditions at different circadian stages could influence these fluctuations. Young mature (10 weeks) and old (22 months) Wistar rats were initially exposed to light-dark cycles 12:12 during 4 weeks, and secondly 18:6 for either one week or six weeks. Erythromycin N-demethylase (CYP3A-dependent), 7-ethoxycoumarin O-deethylase (CYP1A-dependent) and aniline 4-hydroxylase (CYP2E-dependent) activities were determined in liver and kidney microsomes at different hours after darkness onset (HADO). In addition, liver and kidney GSH, GSHPx, ATP, TBARS were determined. During the LD 12:12 cycle, while no significant modification was observed in CYP1A- and 2E-dependent enzyme activities as functions of HADO, erythromycin N-demethylase activity (CYP3A-dependent) showed a significant increase during the second third of the dark period in both young and old rats. After switching to a LD 18:6 cycle, this variation was still observed during second third of the dark period, to a lesser but still significant degree, with no difference between one week and six weeks exposure to the new photoperiod. It can be noted that the old rats showed a significantly lower level of erythromycin N-demethylase activity than the young rats, in parallel to a decrease in GSH, GSHPx and ATP, and an increase in TBARS. These results confirm the lower resistance of old animals to oxidative stress. The observed variations in metabolism parameters underline the need for study designs in pharmaco-toxicology taking into account the possible risks induced by circadian changes, especially in aged subjects.

Aging↗
PubMed2003

[Oral anticoagulants in the elderly].

PURPOSE: Atrial fibrillation and venous thromboembolism are particularly frequent in the elderly. Whether or not prescribe oral anticoagulant treatment in the elderly is therefore a common question for the physician. Despite the benefits of anticoagulation demonstrated in clinical trials, oral anticoagulant therapy is underused in the elderly. CURRENT KNOWLEDGE AND KEY POINTS: Indications for oral anticoagulation are discussed specifically in the elderly with a literature review. Only the length of anticoagulation treatment after a venous thromboembolism remained a purpose of discussion regarding the severity of the pathology. The frequency of systemic thromboembolism in nonvalvular atrial fibrillation is increasing with age. Oral anticoagulation reduces this risk. This benefice is to compare with the increasing rate of major bleeding complications in the elderly and in patient who had stroke, hyper-tension, diabetes mellitus or gastrointestinal bleeding. The objective of this article is to focus on the mode to measure oral anticoagulant benefice/risk ratio in the elderly and to propose several ways to minimize the risk for bleeding. FUTURE PROSPECTS AND PROJECTS: The potential drug side effect severity of oral anticoagulation must lead to find the "reasonable" clinical indications in term of benefice/risk ratio and what measures should be take to increase the safety of oral anticoagulation in the elderly. The comprehensive geriatric evaluation should be considered as a decision-aid tool in long-term oral anticoagulation in the frail elderly. Anticoagulation clinics, informatics'-prescription coupled with dose-adaptation decision-aid adapted to the elderly should be helpful in this research of quality. Finally, prescribers education supports must insist on the early course of therapy that is at higher risk of bleeding.

Administration, Oral↗
PubMed2003

Telesurveillance of elderly patients by use of passive infra-red sensors in a 'smart' room.

We have developed an automated surveillance system based on passive infra-red sensors. Eight sensors were installed in a hospital room. A computer automatically captured data from the sensors every night from 21:00 until 06:00 the following morning. The sensors were polled twice per second and when a sensor was activated by movement, the event and time were recorded in a data file. At the end of the surveillance period the program analysed the data and generated a report showing the activities taking place in the room and their times. Four elderly patients were observed for a total of 97 nights. A total of 1637 possible sequences of movements by the patient and the hospital staff were detected. The computer was able to identify 1450 sequences (89%) correctly, in comparison with manual analysis. Only 10 movements (0.6%) were undetected by the system; all were very short sequences (five or six activations of the sensors). The system was generally capable of detecting and classifying all major movements in the room.

Aged↗
PubMed2001

Metabolic alterations without metal accumulation in the ovary of adult Bufo arenarum females, observed after long-term exposure to Zn(2+), followed by toxicity to embryos.

Long-term exposure of aquatic organisms to metals, even those considered micronutrients, may affect their metabolism and produce sublethal effects. We evaluated the effects of long-term exposure of adult amphibian (Bufo arenarum) females to 4 microg/L of Zn(2+) (ZnSO(4) x H(2)O) in Ringer solution on the concentration of Zn and Fe, the activity of the key enzyme of the pentose phosphate pathway glucose 6-phosphate dehydrogenase, and glutathione content, both in the liver and ovary of these animals. We also performed early embryonic development studies by in vitro insemination from control and treated females. Zn exposure rendered lower Zn concentrations in the ovaries than did exposure of animals to Ringer solution without metal addition (97 +/- 50 versus 149 +/- 46 Zn microg/wet tissue g). Zn and Fe concentration correlation was positive and linear in the ovary, but was negative and nonlinear in the liver of the studied females. The activity of the enzyme glucose 6-phosphate dehydrogenase decreased (0.0599 +/- 0.0109 versus 0.0776 +/- 0.0263 micromol of NADPH/min x mg of proteins) and the endogenous glutathione content increased (0.027 +/- 0.005 versus 0.018 +/- 0.007 mg/10 mg of proteins) in the ovary but remained unaltered in the liver as a consequence of Zn treatment. Our results suggest the existence of different mechanisms of regulation of Zn and Fe concentrations in the ovary and in the liver of adult B. arenarum females. Binding of Zn to low-molecular-weight proteins, as metallothioneins, may occur in the liver, thus protecting this organ from toxic effects. In the ovary high-molecular-weight proteins, like glucose-6-phosphate dehydrogenase, should be able to bind Zn, leading to oxidative stress responsible for the observed increase in endogenous glutathione content. Inhibition of the pentose phosphate pathway in the ovary by Zn can be responsible for the reproductive failure that we detected through embryos survival studies during early life stages: 81.3 +/- 6.3% of embryos from control females survived versus 63.1 +/- 13.8% of embryos from Zn-treated females at the branchial circulation stage of development.

Animals↗
PubMed2001

[Thoracic empyema in very old patients: two types of clinical presentation].

INTRODUCTION: Primitive thoracic empyema or empyema secondary to pneumonia represents a significant medical problem necessitating prolonged hospitalizations and increasing the rates of morbidity and mortality. Average patient age is 55 years and remains rare in very old patients (> 85). We report here two observations in very old patients, pointing out the diversity of the clinical presentation. EXEGESIS: Empyema thoracis is classically associated with underlying diseases. It is often polymicrobial but Gram-positive bacteria and anaerobes are more frequent than Gram-negative bacteria. The clinical presentation may be aspecific without any parameters in favor of infectious disease: the rapidity of pleural drainage and antibiotic therapy are the main prognostic factors. CONCLUSION: Because of the diversity of clinical presentation in the elderly population, and because of the efficiency of rapid treatment, geriatric physicians should perform an examination of pleural fluid when pleural effusion is unknown.

Aged↗
PubMed2001

[Surgical decompression treatment of leprous neuritis at the Bom-Pastor Hospital (Brazilian Amazonia)].

PURPOSE: Only leprosy resource centres undertake surgery for neuritis. Patients' accessibility to this surgical procedure is poor because these centres are often far from their homes. The aim of our work is to study the feasibility of neuritis surgery in the field. METHODS: A surgeon trained in this surgery was recruited by Bom-Pastor hospital in Brazilian Amazonia, which is located 400 km away from the leprosy resource centre. Patients operated from May 1996 to December 1997 were enrolled in this retrospective study. RESULTS: A total of 45 operations were carried out during 17 procedures on 13 patients, among which 12 were multibacillary cases. The decompression surgery was performed with a median delay of 1 year after leprosy diagnosis and 3.5 months after the neuritis diagnosis. Among 17 operations, 14 were performed for painful neuritis of recent onset unsuccessfully treated with corticoids or recurring during the month after corticoids were withdrawn. The other three operations were performed for long-standing neuritis with paralysis and deformity. Pain was relieved in all the cases of recent neuritis, except for one patient who suffered from a serious steroid-dependant erythema nodosum leprosum. An improvement of motor function was observed in one out of three patients with long-standing neuritis. Adverse effects were few: a scar infection with a rapid recovery and a keloid scar. Two neurites recurred 2 and 10 months after the surgery. CONCLUSIONS: In an endemic leprosy region, field access to surgery for neuritis appears to prove real progress in the management of leprosy neuritis.

Adolescent↗
PubMed2001

Lack of effect of single high doses of buprenorphine on arterial blood gases in the rat.

High dose buprenorphine, a potent semisynthetic agonist-antagonist for opiate receptors, is now used in substitution treatment of human heroin addiction. Deaths have been reported in addicts misusing buprenorphine. We determined the median lethal dose (LD(50)) and studied the effects of high doses of intravenous buprenorphine on arterial blood gases in rats. Male Sprague-Dawley rats were administered buprenorphine intravenously to determine the LD(50) using the up-and-down method. Subsequently, catheterized groups of 10 restrained rats received no drug, saline, acid-alcohol aqueous solvent (required to dissolve buprenorphine at a high concentration), or 3, 30, or 90 mg/kg of buprenorphine intravenously. Serial arterial blood gases were obtained over 3 h. The LD(50) determined in triplicate was 146.5 mg/kg (median of 3 series, range: 142.6-176.5). The mean dose received by surviving animals was 96.9 +/- 46.7 mg/kg. There was a significant effect of the acid-alcohol aqueous solvent on arterial blood gases. Excluding the solvent effect, 3, 30, and 90-mg/kg buprenorphine doses had no significant effects on arterial blood gases. The toxicity of intravenous buprenorphine in adult rats, assessed by the LD(50), is low. These data are consistent with a wide margin of safety of buprenorphine. The mechanism of death after the intravenous administration of a lethal dose of buprenorphine remains to be determined.

Animals↗
PubMed2001

A preliminary study of the feasibility of wound telecare for the elderly.

We have developed a method for remote wound assessment in the elderly. Wound images were taken with a digital camera at a resolution of 640x480 pixels. JPEG compression was then used to produce images of about 100 kByte. Selected clinical data were transmitted by email, together with standardized digital images of wounds. The remote physician then read the clinical data and viewed the digital images on a 38 cm colour display monitor, at a resolution of 800x600 pixels, in 16-bit colour, using standard software. Three elderly inpatients with pressure sores or leg ulcers had both bedside and remote examinations, by different physicians. The diagnosis and therapeutic recommendations proposed after each of the two examinations were compared qualitatively. There was reasonable agreement between the two physicians in the assessment of wound size, anatomical classification, wound bed and status of infection. However, the lack of palpation represented a major limitation to remote wound assessment, despite the use of probes to delineate the depth of any opening in the wound bed.

Aged↗
PubMed2000

Nutritional (n-3) polyunsaturated fatty acids influence the behavioral responses to positive events in mice.

The effect of (n-3) polyunsaturated fatty acid (PUFA) diet deficiency on behavioural responses to appetitive events was assessed in OF1 mice. Pups fed the same diet (deficient in alpha-linolenic acid or a standard control diet) as their dams were used aged 7 to 11 weeks. In a free choice model, the preference for a sucrose solution in both males and females was significantly lower in deficient than in control mice. Morphine conditioned place preference was obtained with the two diets at 8 and 16 mg/kg morphine, but the lower dose of 4 mg/kg induced a place preference in control but not in (n-3) deficient mice. Taken together, these results suggest that a nutritional (n-3) PUFA deficiency can alter the responsiveness to appetitive events.

Animals↗
PubMed2000

Morphine-induced sensitization of locomotor activity in mice: effect of social isolation on plasma corticosterone levels.

This study examined the influence of social isolation on behavioural sensitization to the locomotor effect of morphine and the link between this behaviour and plasma corticosterone concentrations. Four weeks isolation induced an increase in the locomotor effect of morphine. In social and isolated mice, repeated administrations (6) of morphine (one injection every 3 or 4 days) followed by 3 h in an actimeter induced behavioural sensitization to the locomotor effect of morphine. No interaction was observed between social isolation and behavioural sensitization to morphine. Resocializing previously isolated mice for 3 weeks reduced the morphine-induced locomotor effect without altering the behavioural sensitization. Corticosterone plasma levels were more increased (416%) in mice isolated 5 weeks than in mice isolated for 2 weeks (243%) and they return to the control levels following 3 weeks of resocialization. Since there was no interaction between the increase in morphine locomotor effect induced by social isolation and the morphine-induced behavioural sensitization, it is suggested that each of these two events acts independently. Whether or not a common mechanism (plasma corticosterone levels?) partly underlies both effects, the result resembles a simple additive effect.

Adrenal Cortex↗
PubMed2000

Absence of the effects of 50 Hz magnetic fields on the progression of acute myeloid leukaemia in rats.

PURPOSE: As the most recent epidemiological studies provide no definite conclusions about the effects of 50/60 Hz magnetic fields (MFs) on the incidence of leukaemia in humans, animal models in a well-controlled environment are useful for evaluating the possibility of an association between MFs and leukaemia. The present study was designed to determine whether 50 Hz magnetic fields can alter the progression of leukaemia. MATERIALS AND METHODS: A well-characterized model of transplantable acute myeloid leukaemia in rats was used for the first time. This model is closely related to human acute myeloid leukaemia, the type most frequently reported in epidemiological studies of adults. After leukaemic cell implantation, rats were exposed to a sinusoidal 50 Hz MF of 100 microT for 18 h a day, 7 days a week, throughout leukaemia progression. The parameters investigated were: survival time, body weight, haematologic parameters, infiltration of blood, bone marrow, spleen and liver by leukaemic cells. RESULTS: The results showed no significant changes (p > 0.05) in leukaemic MF-exposed versus unexposed rats for any of the parameters involved in leukaemia progression. CONCLUSION: These data do not support the hypothesis that 50 Hz magnetic fields influence leukaemia progression in humans.

Adult↗
PubMed2000

Can 50 Hz magnetic fields alter iron metabolism and induce anaemia?

UNLABELLED: PURPOSE. Some changes in tissue iron concentration have been reported in animals exposed to electromagnetic fields. In other studies, variations in the haemoglobin level were occasionally observed. In the present experiment, the effects of exposing a rat to a 50 Hz magnetic field (MF) were therefore investigated for the possible induction of anaemia due to changes in iron metabolism. MATERIALS AND METHODS: Male Brown Norway rats (n=225) were exposed to a sinusoidal 50 Hz MF of 500 microT for 15 weeks. Haematological parameters, differential bone marrow cell counts and sideroblasts were investigated. Blood parameters of iron metabolism were measured. Iron concentration and total iron content were also determined in the spleen and liver, to assess iron storage in these organs. RESULTS: Significant differences between the exposed and control rat were only detected for iron storage in the spleen, and for the percentage of bone marrow cells of the red cell lineage. CONCLUSION: The changes observed were not associated with anaemia during the 15 weeks of MF exposure. However, the decrease in bone marrow cells of the red cell lineage and the changes in iron storage detected at the end of the experiment did not allow the possibility to be ruled out that exposure to 50 Hz MFs may induced delayed biological effects.

Anemia↗
PubMed1999

Effect of social isolation on the metabolism of morphine and its passage through the blood-brain barrier and on consumption of sucrose solutions.

RATIONALE: We have previously shown that place preference conditioning to morphine was observed in social mice at the dose of 8 mg/kg, whereas 4 weeks of isolation impairs the place preference conditioning to morphine (8-100 mg/kg). OBJECTIVE: The present study, aimed at explaining this phenomenon, tested three hypotheses: firstly, a reduced sensitivity to reinforcers induced by isolation; secondly, a difference in morphine disposition in isolated and social mice; thirdly, an altered blood-brain barrier transport of morphine in isolated mice. METHODS: In the sucrose experiments, mice had the choice (for 24 h) between a bottle containing tap water and a bottle containing a sucrose solution. Three sucrose concentrations were used: 0.5, 1 and 2% (weight/weight). In the morphine disposition experiments, the plasma levels of morphine and of morphine-3-glucuronide (M3G) were measured for 240 min. The brain concentrations of morphine was measured at 15 and 30 min. The passage of morphine through the blood-brain barrier was measured using a method modified from that of Takasato (1984). RESULTS: The preference for the sucrose solutions was significantly greater in isolated than in social mice for the concentration of 2%. Isolation reduced the plasma levels of morphine and of M3G, but did not alter the brain concentration of morphine. The passage of morphine through the blood-brain barrier was altered by isolation in neither of the eight structures examined. CONCLUSIONS: We conclude that the behavioural effect of isolation observed in the conditioned place preference to morphine may depend on changes both in morphine disposition and in the sensitivity to reinforcers in isolated mice.

Analgesics, Opioid↗