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Biomedical subjects

M Morena

Publications and source records attributed to M Morena.

At least 19 recordsLinked to original sources
PubMed2006

Beta2-microglobulin, a uremic toxin with a double meaning.

beta(2)M is a strong and independent indicator of hemodialysis patient outcomes and an excellent surrogate for middle molecules, and deserves to be routinely monitored and incorporated into dialysis adequacy targets. beta(2)M has a double meaning, reflecting both dialysis efficacy in terms of solute mass transfer and patient bioactivity. The work of Ward et al. in this issue warrants a study to test the hypothesis that long daily hemodiafiltration treatment would be the optimal renal replacement modality to improve dialysis patient outcomes.

Body Fluid Compartments↗
PubMed2005

Anti-oxidants reverse uraemia-induced down-regulation of mitochondrial membrane potential and interleukin-10 production.

BACKGROUND: The anti-inflammatory cytokine, interleukin-10 (IL-10), has potent immunomodulatory effects. We hypothesized that previously reported defective synthesis of IL-10 by immunocompetent cells exposed to a uraemic milieu may be due to impaired mitochondrial membrane potential (MMP). MATERIALS AND METHODS: The human promonocytic THP-1 cell line was differentiated to monocytes and incubated with pooled control or uraemic plasma with and without catalase or N-acetyl L-cysteine (NAC). Basal hydrogen peroxide (H(2)O(2)) production was measured by flow cytometry. To measure MMP, cells were stained with rhodamine 123 (Rh123) and the uptake of Rh123 assessed by flow cytometry. To assess the relative contribution of the NADPH oxidase and mitochondrial electron transport chain (ELT) to endotoxin (ET)-stimulated IL-10 production among monocytic cells, cells were incubated with and without a selective NADPH oxidase inhibitor, apocynin and mitochondrial ELT inhibitors, diphenyliodinium and rotenone, washed and ET-stimulated IL-10 production was measured. In other experiments, cells were incubated with pooled control or uraemic plasma in the presence or absence of antioxidants followed by overnight incubation with ET. IL-10 production by monocytes in the cell supernatant was then quantified. RESULTS: Basal H(2)O(2) production was significantly higher among differentiated THP-1 cells exposed to uraemic plasma compared with normal plasma (180.57 +/- 10.24 vs. 41.57 +/- 8.98 MCI; P = 0.02). Uraemic plasma also down regulated MMP (4.60 +/- 1.28 vs. 8.00 +/- 1.59 MCI with normal plasma; P = 0.03). Both diphenyliodinium and rotenone, selective inhibitors of the mitochondrial ELT, inhibited ET-stimulated IL-10 production. In contrast, apocynin, a selective NADPH oxidase inhibitor, did not inhibit ET-stimulated IL-10 production. Further, ET-stimulated IL-10 production by cells incubated with uraemic plasma was significantly lower when compared to cells exposed to normal plasma. Pre-incubation with catalase and NAC restored uraemia-induced down regulation of MMP. In addition, ET-stimulated IL-10 production by cells incubated with uraemic plasma was also restored by both catalase and NAC. CONCLUSIONS: Our observations suggest that ET-stimulated IL-10 synthesis by monocytic cells is mitochondrial ELT-dependent and NADPH oxidase-independent. Monocytic cells exposed to a uraemic environment exhibit higher basal ROS production, lower MMP, and impaired ET-stimulated IL-10 synthesis. Anti-oxidants restore MMP and up-regulate ET-stimulated IL-10 synthesis.

Antioxidants↗
PubMed2004

Mechanism of in vitro heme-induced LDL oxidation: effects of antioxidants.

BACKGROUND: Heme protein toxicity, owing to generation of reactive oxygen species most likely by direct interaction between heme iron and hydrogen peroxide (H2O2), may be involved in various pathologies, including atherogenesis and pigmentary acute renal failure. The aim of this study was to investigate the mechanism of heme cytotoxicity and the effects of antioxidant therapies in an in vitro model of heme-induced low-density lipoprotein (LDL) oxidation. MATERIALS AND METHODS: Human LDLs were exposed to heme, iron (Fe), protoporphyrin (PPIX) and PPIX-Zinc (Zn) with or without H2O2. Lipid peroxidation was monitored by measurement of conjugated diene formation (at the 234-nm absorbance). The effect of various antioxidants, such as vitamin E and vitamin C, reduced glutathione (GSH), and oxidized glutathione (GSSG), mannitol and desferoxamine (DFO) was further investigated in the established in vitro model of LDL oxidation. RESULTS: Incubation of LDLs in the presence of heme/H2O2 induced lipid peroxidation with the optimal oxidation rate being at 5 microm heme/100 microm H2O2 doses. By contrast, incubation of LDL with H2O2, Fe, Fe/H2O2, PPIX, PPIX/H2O2, heme or PPIX-Zn did not initiate any LDL oxidation. In vitro, the vitamin E load protected native LDLs against heme/H2O2 oxidative modifications. Incubation of LDLs with increasing doses of vitamin C, GSH and DFO conferred a dose-dependent protection, while mannitol and GSSG had no effect. CONCLUSIONS: Initiation and propagation of heme-induced lipid peroxidation is not mediated by a Fenton reaction but depends on specific interactions between heme and H2O2. It may result from the generation of ferryl and perferryl radicals derived from hemic Fe and H2O2 interactions. A protective effect of vitamins E, C, GSH and DFO was demonstrated in this model.

Antioxidants↗
PubMed2003

[Is C-reactive protein a marker of inflammation?].

C-reactive protein (CRP) is the prototype of acute-phase protein which is secreted by the liver in response to a variety of inflammatory cytokines. Levels of CRP can increase up to 1000-fold very rapidly after the onset of inflammation and decrease just as rapidly with the resolution of aggression. CRP is a member of the ancient highly conserved pentraxin family of proteins and it is arranged in a cyclic homopentameric structure. The important role of CRP in innate immunity is largely due to its opsonizing abilities, its capability to activate human complement and to bind to immunoglobulin G receptors. CRP can bind phosphocholine largely present in bacterial membranes, cell membrane and lipoproteins, in addition CRP can recognize nuclear constituent in damaged cells. CRP can activate C3 convertase through the classical pathway but not C5 convertase resulting in generation of opsonic complement fragments. Interactions of CRP with Fc receptors lead to the generation of proinflammatory cytokines and reactive oxygen species by monocyte/macrophage while inhibit neutrophiles functions. Recently, CRP was demonstrated to play an active role in atherogenesis and it has been largely proven that a microinflammatory state as defined by a moderate increase in CRP (up to 3 mg/l), is associated with an increased risk for arterial disease. Moreover it has been postulated that CRP may be a useful tool for monitoring drug therapy.

C-Reactive Protein↗
PubMed2003

[Vascular access, an underestimated source of inflammation in dialysis patients].

The surveillance of inflammation in dialysis patient, by means of sensitive markers such as CRP, is strongly recommended in a continuous quality improvement treatment approach. Chronic inflammation being deleterious via several pathways including malnutrition, accelerated arteriosclerosis and beta 2M-amyloidosis, microinflammation must diagnosed and corrected as soon as possible in dialysis patients. Vascular access represents an underestimated source of inflammation in hemodialysis patients. In the absence of organic cause of inflammation, the vascular access should be always incriminated and meticulously investigated. Withdrawing the suspected prosthetic or unused material (PTFE or catheter) should be considered as the best way of correcting the inflammation and restoring the recombinant erythropoietin (EPO) activity in the dialysis patient.

Acute Disease↗
PubMed2002

[Oxidative stress, hemo-incompatibility and complications of long-term dialysis].

Oxidative stress which results from an imbalance between oxidant production and antioxidant defense mechanisms is now a well recognized pathogenesis factor that could be implicated in the hemodialysis (HD)-related pathology. This review focuses on: 1) factors that may be responsible for oxidative stress in HD patients (hemoincompatibility of the dialysis system--hemoreactivity of the membrane and trace amounts of endotoxins- and uremia per se); 2) implication of such phenomenon in long term complications including anemia, amyloidosis, accelerated atherosclerosis and malnutrition and finally and 3) prevention ways consisting in improving the hemocompatibility of the dialysis system and supplementing the deficiency patients with antioxidants.

Anemia↗
PubMed2001

[Dialock: results of a French multicenter study].

INTRODUCTION: By offering a rapid and convenient vascular access option for hemodialysis, permanent catheters are increasingly used in ESRD patients. Indeed, permanent catheters are associated with an increased risk for complications. Moreover, catheter bearing spoils the self body image and may alter the quality of life of dialysis patients. Implantable port catheter device, recently introduce in dialysis, may offer an attractive option, able to reduce most of infectious risk and inconveniences of the permanent catheters. PATIENT AND MATERIAL: The Dialock (Biolink) device was evaluated in a multicenter French trial. Twelve dialysis facilities enrolling 51 ESRD patients (male 28, female 23, age 56 +/- 2 years) participated in this trial. Dialock devices were inserted in patients for whom a permanent venous catheter was indicated. The cumulative experience was 56.8 years-patient. The technical survival (intent to treat) of Dialock devices was 85% at two years. Blood flow were 299 +/- 7 ml/min. Dialysis adequacy was achieved in all patients without altering dialysis schedule (3 sessions per week, 240 +/- 30 min each). Dialysis dose (K(/Vdp) delivered was 1.3 +/- 0.2. Satisfaction of patients and nursing staff was achieved in 75% of cases. Normalized incidence of complications (events for 1000 patient-days) in the evaluation phase (II) were as follows: hematoma and/or small bleeding (2.1), bacteremia (1.1), device infection (0.2), skin necrosis (0.1). A significant reduction of the infection and hematoma incidence rate was noticed when heparin lock was substituted for an non hemorrhagic antithrombotic locking solution (fragmented heparin or sodium citrate). This observation tend to accreditate the hypothesis that port catheter infection occurs via a transluminal bacteria passage. CONCLUSION: The Dialock device, offers a new and comfortable hemodialysis vascular access for ESRD patients. Performances are in agreement with those needed to achieve adequate dialysis. The regular use of dual antithrombotic-antiseptic catheter locking solution seems to be necessary to prevent any bacterial contamination.

Anticoagulants↗
PubMed2000

Protective effects of high-density lipoprotein against oxidative stress are impaired in haemodialysis patients.

INTRODUCTION: Cardiovascular diseases represent the major cause of mortality in haemodialysis (HD) patients. Oxidized low-density lipoprotein (Ox-LDL) is a major cardiovascular risk factor, implicated in atherosclerotic plaque formation. It has been suggested that high-density lipoprotein (HD) has the capacity to reduce the oxidative modifications of LDL. The aim of this study is to analyse the protective effects of HDL in HD patients. METHODS: In vitro copper-induced LDL oxidation was evaluated in 12 patients with chronic renal failure (mean age 61.0+/-12.8 years) and compared to 25 healthy subjects (mean age 57.3+/-19.2 years). LDL were incubated in oxygen-saturated PBS, LDL oxidation was initiated by Cu (II) in the presence and absence of HDL and assessed by measuring the absorbance (abs) increase at 234 nm due to conjugated diene formation. Duration of lag time, maximum velocity (V(max.)) of lipid peroxidation, oxidation slope and half-time of maximum diene formation (T (1/2)) were obtained by kinetic modelling analysis. RESULTS: HDL (1.06+/-0.31 vs 1.23+/-0.39 mmol/l) and Apo AI (1. 17+/-0.39 vs 1.49+/-0.20 g/l) levels were decreased in HD patients. In the absence of HDL, LDL obtained from HD patients showed an enhanced susceptibility to oxidation in vitro as demonstrated by the significant decrease in lag time (54.5+/-22.2 vs 79.4+/-37.8 min) and a significant increase in V(max.) (0.026+/-0.006 vs 0.017+/-0. 005 abs/min). In all cases, HDL (from 0.1 to 2 microM) prevented LDL oxidation in vitro; however, this effect was significantly reduced in HD patients: increase in lag time 54.2% vs 150.4% in HD vs controls; increase in T (1/2) 52.2% vs 124.6% in HD vs controls; decrease in V(max). 13.5% vs 38.5% in HD vs controls. CONCLUSIONS: These results suggest that qualitative abnormalities such as an impairment of HDL-associated enzymes are associated with a decrease of HDL levels during HD. Hence, in addition to the known impairment of reverse cholesterol transport, the reduction of HDL protective capacity against oxidative stress could be involved in the development of HD-induced atherosclerosis.

Adult↗
PubMed2000

Why hemodialysis patients are in a prooxidant state? What could be done to correct the pro/antioxidant imbalance.

Oxidative stress which results from an imbalance between reactive oxygen species production and antioxidant defense mechanisms is now well recognized in hemodialysis (HD) patients and could be involved in dialysis-related pathologies such as accelerated atherosclerosis, amyloidosis and anemia. In order to evaluate the rationale for preventive intervention against oxidative damage during HD, we review the factors that are implied and may be responsible for the imbalance between pro- and antioxidative mechanisms. The inflammatory state mainly due to hemobioincompatibility of the dialysis system plays a critical role in the production of free oxygen radical species contributing by this way to worsen the prooxidant status of uremic patients. Two factors largely contribute to the stimulation of the NADPH oxidase: hemoreactivity of the membrane and trace amounts of endotoxins. The antioxidant system is severely impaired in uremic patients and gradually altered with the degree of renal failure. HD could further impair this antioxidant system mainly by losses of (a) hydrophilic unbound small-molecular-weight substances such as vitamin C, (b) trace elements and (c) enzyme-regulatory compounds. Two main axes may be proposed in order to prevent and/or to decrease oxidative stress in HD patients. One consists in improving the hemocompatibility of the dialysis system mainly by using a dialyzer with low hemoreactivity and ultrapure, sterile, nonpyrogenic dialysate. The other consists in supplementing the deficiency patients with antioxidants. This could be achieved by oral or perdialytic supplementation. Vitamin E could be bound on dialyzer membrane. Alternatively, hemolipodialysis consists in loading HD patients with vitamin C or E via an ancillary circuit made of vitamin E-rich liposomes. The presence of liposomes could also facilitate the removal of hydrophobic prooxidative substances.

Antioxidants↗
PubMed2000

Microbiologic purity of dialysate: rationale and technical aspects.

Dialysate purity has become a major concern in hemodialysis since it has been shown that microbial-derived products were stimulating the production and the release of proinflammatory cytokines in hemodialysis patients. This chronic microinflammatory state induced by hemodialysis has been putatively implicated in the development of dialysis-related pathology. In order to prevent risk related to these offenders and to reduce patient/dialysis interaction, it appears highly desirable to use ultrapure dialysis fluid aiming at sterility and apyrogenicity on a regular basis. Ultrapure dialysate results from a complex chain of production where purity grade relies on the weaker link of this chain. Technical aspects and pitfalls in the production of ultrapure dialysate are summarized in this paper. Production of ultrapure dialysate may be achieved on a routine basis, provided adequate components are used, and hygienic handling is regularly ensured. It includes the use of ultrapure water, clean and or sterile electrolytic concentrates (liquid or powder), implementation of ultrafilters on hemodialysis machines, microbiologic monitoring and hygienic handling of the chain with frequent disinfection. Safety and reliability of ultrapure dialysate production relies on a continuous quality assurance process, where results are coupled to corrective action in a feedback loop process.

Dialysis Solutions↗
PubMed1999

Dialock: a new vascular access device for extracorporeal renal replacement therapy. Preliminary clinical results.

BACKGROUND: Vascular access, a vital tool for end-stage renal disease patients, remains a weak component of extracorporeal renal replacement therapy (RRT) and the first cause of morbidity. Permanent catheters proposed as an alternative to permanent AV fistulae are associated with a significant risk of infection. A subcutaneously implantable chamber connected to permanent catheter appears highly desirable to reduce such hazards. METHODS: Dialock, a metallic port-like valve device connected to permanent silicone twin catheters has been developed (Biolink Corp, Middleboro, MA, USA). After being implanted subcutaneously below the clavicle, Dialock provides a linear flow passage to two Silastic catheters placed in the right atrium via the right internal jugular vein. The valve is accessed percutaneously each dialysis session with needle cannulae that functionally convert the device into twin catheters. Interdialytic patency of the catheters is ensured by antithrombotic lock (heparin or low-molecular-weight heparin). RESULTS: Dialock was implanted in 10 ESRD patients (64+/-12 years) under general anaesthesia, with almost immediate use for HD. RRT consisted of three HD sessions per week lasting 4 h; 699 HD sessions were performed. Average duration of use was 5.7 patient-months (1.3-9.6 months). Patient satisfaction was evident in all cases. Three episodes of bacteraemia occurring in the early phase of the study were cured by appropriate antibiotics. No device was removed because of infection. Skin condition at the puncture sites has remained satisfactory in all patients. Nurse training for cannulating was brief (2-3 x). Effective blood flow was 307+/-3.3 ml/min, with a venous pressure of 195+/-39 mmHg and a recirculation rate of 6.7+/-0.8%. Effective Kt/V dp delivered was 1.36+/-0.03 with a nPCR of 1.20+/-0.005 g/kg/day. Haematoma and a small amount of bleeding of the skin puncture sites observed in the initial period of the study were effectively prevented by reducing heparin lock volume. CONCLUSIONS: The Dialock device offers a new and interesting vascular access alternative for haemodialysis bridging the 'gap' between permanent catheters and arteriovenous fistulae. Dialock's place in the vascular access strategy for haemodialysis patients deserves further long-term clinical studies.

Adult↗
PubMed1999

Imbalance of oxidants and antioxidants in haemodialysis patients.

Dialysis-related pathology (DRP) observed in long-term haemodialysis patients is increasingly reported. Among DRP manifestations, cardiovascular disease is the most frequent, being the first cause of mortality in haemodialysis patients. Alterations in lipid metabolism and oxidative stress are recognised as major risk factors that could be prevented or reduced by optimal therapy. In order to evaluate the rationale for preventive intervention against oxidative damage we review the factors that are implied and may be responsible for the imbalance between prooxidative and antioxidative mechanisms in haemodialysis patients. Oxidative stress resulting from this imbalance is responsible for increasing stress markers and enhancing susceptibility to LDL oxidation. Factors implied in this prooxidative state belong to four groups: (1) uremia and comorbid status of the end stage renal disease (ESRD) patient; (2) losses of antioxidant substances via the dialysis; (3) haemoincompatibility of the dialysis system; (4) adjuvant therapy. Such prooxidant status could have further deleterious consequences since it has been recently shown that antioxidant status could modulate cell functions such as reactive oxygen species (ROS) production, adhesive molecule expression and/or cell proliferation. Preventive modalities, including use of biocompatible membrane, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of ROS and oxidatively-modified substances, would appear highly desirable to reduce complications of long-term dialysis patients.

Antioxidants↗
PubMed1999

[Kinetic modeling of LDL oxidation using software (NELOP program) and validation in a population at vascular risk].

Oxidized LDL (low density lipoprotein) are considered to be the major initiating event in atherogenesis. In vitro models have been studied but no mathematic modeling can assess quantitatively the oxidability of LDL and antioxidant effects. We have developed a mathematic modeling allowing quantification of different kinetic parameters to LDL oxidation. This model has been validated by means of a software (software NELOP) in normal population (HV) and in a cardiovascular risk population, hemodialysis (HD). LDL are collected and purified by sequential ultracentrifugations from 12 healthy volunteers and hemodialysis patients. LDL oxidability (0.1 microM) is initiated by 5 microM copper and monitored continuously by conjugated diene production. All parameters are evaluated and correlated to those obtained by NELOP. Significant correlations between measured and calculated parameters (Vmax: r2 = 0.99, p < 0.05) allow to validate NELOP in both populations. Our results show that hemodialysis LDL present an enhanced susceptibility to copper induced oxidation (lag time: 96.6 +/- 48.6 mn in HV versus 54.5 +/- 22.2 mn in HD). NELOP seems to be a useful tool to evaluate LDL oxidation in cardiovascular risk populations.

Aged↗
PubMed1995

[Carcinomatous meningitis. Presentation of 3 cases].

Meningeal carcinomatosis is characterized by diffuse infiltration of the leptomeninges by metastatic cancer in patients usually with a previous history of malignancy. Primary tumors are adenocarcinomas of the breast or lung, or malignant melanoma. The clinical presentation is pleomorphic and commonly affects the cerebral hemispheres, the cranial nerves, or spinal cord and its roots. Diagnosis is confirmed by the presence of the malignant cells in the cerebrospinal fluid (CSF). Computed tomography (CT) and magnetic resonance (MRI) show abnormal findings including ventricular dilatation and small enhancing lesions along the CSF space. Despite radiotherapy and chemotherapy, vital prognosis remains bad and the treatment is useful in improving the quality of life. Three cases presented here emphasize once again the important fact that meningeal carcinomatosis remains a very difficult diagnosis; several lumbar punctures were sometimes necessary, and cerebral fluid studies cannot yet be replaced by other diagnostic techniques like contrast enhanced CT or MRI with gadolinium.

Adenocarcinoma↗
PubMed1994

Response of arm flexor muscles to magnetic and electrical brain stimulation during shortening and lengthening tasks in man.

1. The responses of the brachioradialis and biceps brachii muscles to non-invasive magnetic and electrical stimulation of the human motor cortex have been investigated during performance of different tasks. 2. Both muscles were simultaneously active during elbow flexor isometric torque, or forearm flexion lifting a weight (shortening contraction), or extension breaking the fall of the weight (lengthening contraction). The forearm extensor triceps brachii muscle was not engaged in any task. By using different weights, comparable levels of EMG activity were obtained in the same muscle across tasks. 3. Both magnetic (7 subjects) and electrical (3 subjects) brain stimulation (at about 1.5 times the motor threshold) produced larger responses during shortening, and smaller responses during lengthening, in the brachioradialis muscle with respect to isometric contractions, in spite of equal background EMG levels. Responses evoked in the biceps brachii by either stimulation mode were smaller during lengthening but not significantly enhanced during shortening. No consistent differences in the task-related modulation of the responses were present between electrical or magnetic stimulations. No significant changes in the evoked responses occurred during passive elbow flexion or extension. 4. In three subjects, the H reflex was evoked in the brachioradialis by stimulation of the radial nerve during performance of the same tasks. The pattern of task-related modulation of the reflex amplitude paralleled that obtained for brain stimulation. 5. The opposite modulation induced by the shortening and lengthening tasks both in magnetically and electrically evoked motor responses, and in the H reflex, suggests that task-related changes in excitability of the cortical neurones play a minor role.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Motor evoked potentials following cervical electrical stimulation in brachial plexus lesions.

The diagnostic relevance of recording motor evoked potentials (MEPs) after electrical stimulation of the cervical region, as compared with conventional needle electromyography (EMG), was evaluated in 26 patients with brachial plexus (BP) damage of different aetiology, severity and topography. MEP abnormalities (absence or latency increase) were observed in at least one muscle of all the patients, with a global incidence of 61.5% of the muscles examined. Neurogenic EMG signs were present in all but one patient with an incidence of 62.2% of the muscles examined. Combining the two methods, the global incidence of abnormalities rose to 69.9%. MEP abnormalities were consistent with the clinical topography and severity of BP lesions and were fairly parallel with EMG findings. Recording MEPs after percutaneous electrical stimulation of the cervical region may be regarded as a rapid, non-invasive method for quantitative electrophysiological assessment of BP damage.

Adolescent↗