Search PubMed⌕ Search

Biomedical subjects

N Simon

Publications and source records attributed to N Simon.

251 records · Page 14Linked to original sources
PubMedDate not supplied

Neonatal gallbladder enlargement and alpha 1-antitrypsin deficiency.

Patients with clinical signs of alpha 1-antitrypsin deficiency in the neonatal period usually present with prolonged obstructive jaundice. We report a patient with alpha 1-antitrypsin deficiency who presented with gallbladder enlargement in the neonatal period. This gallbladder enlargement may be due to cystic duct hypoplasia or atresia, which has been reported in association with alpha 1-antitrypsin deficiency. The diagnosis of alpha 1-antitrypsin deficiency should be considered in neonates with gallbladder enlargement and prolonged obstructive jaundice.

Gallbladder Diseases↗
PubMedDate not supplied

Low glucocorticoid concentrations decrease oxidative phosphorylation of isolated rat brain mitochondria: an additional effect of dexamethasone.

The effects of hydrocortisone, triamcinolone, prednisolone and dexamethasone have been investigated in vitro using mitochondria isolated from rat brain. Respiratory control ratio (RCR), oxygen consumption, ATP synthesis, enzymatic activities of involved complexes and superoxide anion generation have been measured to assess the effects of these drugs. Our data showed that the decrease of RCR induced by glucocorticoids was due to a common inhibition of oxidative phosphorylation (State 3) and of complex V activity and a modification of the proton-fluxes through the mitochondrial inner membrane. These effects were quantitatively limited, since they occurred at concentrations lower than 2 nM. Dexamethasone was the only one able to induce a specific inhibition of complex I activity and to decrease the superoxide anion radical generation. Inhibition of complex V and partial reversion of uncoupling seem to be common properties of glucocorticoids. The theoretical consequence of these inhibitions could be the modulation of the mitochondrial function, oxygen consumption rate, ATP synthase activity and superoxide anion radical production, involved in many patho-physiological phenomena.

Animals↗
PubMedDate not supplied

Oligonucleotide probes for the identification of three algal groups by dot blot and fluorescent whole-cell hybridization.

Photosynthetic pico- and nanoplankton dominate phytoplankton biomass and primary production in the oligotrophic open ocean. Species composition, community structure, and dynamics of the eukaryotic components of these size classes are poorly known primarily because of the difficulties associated with their preservation and identification. Molecular techniques utilizing 18S rRNA sequences offer a number of new and rapid means of identifying the picoplankton. From the available 18S rRNA sequence data for the algae, we designed new group-specific oligonucleotide probes for the division Chlorophyta, the division Haptophyta, and the class Pelagophyceae (division Heterokonta). Dot blot hybridization with polymerase chain reaction amplified target rDNA and whole-cell hybridization assays with fluorescence microscopy and flow cytometry were used to demonstrate probe specificity. Hybridization results with representatives from seven algal classes supported the phylogenetic affinities of the cells. Such group- or taxon-specific probes will be useful in examining community structure, for identifying new algal isolates, and for in situ detection of these three groups, which are thought to be the dominant algal taxa in the oligotrophic regions of the ocean.

Chlorophyta↗
PubMedDate not supplied

[Effects of trimetazidine on altered functions of rat kidney induced by cyclosporine].

A mitochondrial dysfunction has been suggested to explain chronic renal toxicity observed in ciclosporine A therapy. Our study has investigated whether trimetazidine allows inhibition of mitochondrial alteration induced by ciclosporine A. Oxidative phosphorylation was measured by polarography, calcium fluxes by a specific calcium electrode and the mitochondrial swelling by determination of the optical density at 520 nm, using a spectrophotometer. The ciclosporine A effect on the respiratory control was fully inhibited by trimetazidine (EC50 5.10 x 10(-7) M; Emax 11 per cent). Trimetazidine also inhibited the ciclosporine effects on calcium fluxes, i.e. calcium accumulation into the matrix and delay of efflux. Trimetazidine allows a decrease of mitochondrial dysfunction induced by ciclosporine A.

Animals↗
PubMedDate not supplied

Immunological studies in patients with discoid lupus erythematosus.

Disorders of serum proteins, circulating antibodies, immune complexes to the dermo-epidermal junction, B- and T-cell markers from peripheral blood lymphocytes and the suppressor function of peripheral mononuclear cells have been investigated in 106 patients with histologically proven discoid lupus erythematosus (discoid LE). The results confirm that this condition is primarily a localized skin disease with low concentrations of autoantigens and circulating autoantibodies. By contrast, systemic lupus erythematosus (systemic LE) is a multifocal, generalized disease with high concentrations of autoantigens, autoantibodies and immune complexes. The transformation of discoid LE to systemic LE is discussed, and a possible two-hit mechanism is proposed.

Antigen-Antibody Complex↗
PubMedDate not supplied

[Mycophenolate mofetil, a new immunosuppressive agent. Is pharmacokinetic monitoring justified?].

Mycophenolate mofetil is a new immunosuppressive agent which is indicated in combination with cyclosporin A and a corticosteroid for the prophylaxis of acute transplant rejection in patients receiving allogenic renal transplants. It is an ester prodrug rapidly hydrolysed to mycophenolic acid, an active metabolite. The mechanism of action of mycophenolic acid is different from that of other known immunosuppressive drugs: it inhibits the activity of inosine monophosphate deshydrogenase, an enzyme responsible for the de novo pathway of guanosine nucleotide synthesis in B and T lymphocytes and slows down their proliferative response. Should mycophenolic acid plasma concentrations be monitored? To date, all available data are assessed and more particularly:--the doses of 1 or 1.5 g administered twice daily,--a pilot, open-label multicentre study which showed a decreased incidence of acute rejection episodes in patients with steady state AUC0-12 h plasma levels < 40 micrograms.ml-1.h.--adverse events (mainly gastrointestinal, blood and lymphatic disorders) which appear more frequently in patients receiving 3 g/day than in patients receiving 2 g/day and which do not seem to be correlated with plasma concentrations of mycophenolic acid. The examination of these data clearly shows that additional investigations are necessary to better clarify the relationship between plasma mycophenolic acid concentration and side effects in order to provide a scientific rationale for monitoring the plasma concentrations on a regular basis.

Humans↗
PubMedDate not supplied

[Value of protecting mitochondrial functions during treatment with cyclosporin A].

The use of cyclosporin A is often limited by its nephrotoxicity. This dose-dependent toxicity can occur in all kinds of transplantation and is reversed with drug withdrawal. Cyclosporin A induces a vasoconstriction leading to an increase of renal vascular resistance and a reduction of glomerular filtration. Histochemical studies show mitochondrial alterations and an excess of cytosolic and mitochondrial calcium leading to a decrease of ATP synthesis. Two strategies can be evoked for limiting cyclosporin-A-induced nephrotoxicity. First, the use of drugs counteracting the vasoconstriction has been proposed. Second, drugs acting by restoration of ATP synthesis could also be of interest. For example, calcium channel blockers may be used for limiting the Ca2+ fluxes into cells. Another way to protect ATP synthesis is to inhibit the cyclosporin-A-induced increase of mitochondrial Ca2+ concentrations; Trimetazidine has shown its efficiency in vitro for protecting mitochondria against these modifications of Ca2+ homeostasis and is under clinical evaluation.

Animals↗
PubMedDate not supplied

[Mediators involved in the nephrotoxicity of cyclosporin A].

Cyclosporin A-induced nephrotoxicity is a well known adverse effect but its mechanism remains unclear. The understanding of the toxicity mechanism is necessary since the new generation of immunosuppressant drugs (cyclosporin G, FK 506, rapamycin) demonstrates renal toxicity. A renal vasoconstriction occurs with the first administration of cyclosporin and involves several mediators (prostaglandins, renal sympathetic nerves, dopamine. NO, endothelin) which may explain the limited benefit of antagonists. Furthermore, the vasoconstriction explains only haemodynamic modifications and cannot explain histological lesions. New hypotheses involving an alternation of cellular calcium homeostasis suggest alternative investigations to elucidate cyclosporin A nephrotoxicity.

Adjuvants, Immunologic↗
PubMedDate not supplied

[Drug prescription and utilization in Morocco].

The aim of this study was to assess drug prescription and utilization in Morocco 8 years after the statement of the Action Program for Essential Drugs. To evaluate the role of essential drugs in these prescriptions, a study of about 600 prescriptions and questionnaires sent to a random sample of 111 prescribers and a series of visits with the investigator as a neutral observer was undertaken. The average number of drugs prescribed was 3.27, which reflected the feelings of most of the clinicians, for whom 3 drugs per patient is the required number. The number of drugs prescribed is lower in the public health structure (2.0 +/- 0.14 depending on the type of institution: hospital or primary health care centre). Specialties from the national list of essential drugs accounted for 15.48 per cent of all drugs which is to be compared with 16.2 per cent of the clinicians stating knowledge of the action programme for essential drugs. In public structures, these prescriptions ranged between 29.8 per cent and 82.4 per cent of the essential drugs (WHO general list). The length of the visit ranged between 3.27 +/- 0.96 min and 4.87 +/- 1.04 min according to the health centres and prescriptions included at least one antibiotic in 47.5 per cent of cases (25 per cent to 64 per cent). At least one antibiotic was prescribed in 43.3 per cent of cases in the study of prescriptions and 17.3 per cent of prescriptions included at least one injectable drug. The average cost of one prescription was 146.25 dirhams (ranging between 4 and 1200 dirhams = US $17). According to 68.6 per cent of the prescribers, the patients felt there to be a strong relation between efficacy and cost. Among the prescription motivations, cost ranked above availability of the drug and after efficacy.

Drug Prescriptions↗