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Biomedical subjects

G Cremer

Publications and source records attributed to G Cremer.

At least 19 recordsLinked to original sources
PubMed2003

[Recommended techniques for obtaining nail specimens and mycologic diagnosis of onychomycosis].

The diagnosis of onychomycosis requires an assessment of both clinical and laboratory features. The laboratory diagnosis is essential to confirm the fungal origin of the onyxis. Various types of onychomycosis need different methods to obtain a nail specimen. It requires a direct examination to confirm the presence of fungi, and a fungal culture to identify the specific genus and species of the pathogen. A good interpretation of these results is necessary to adapt the therapeutics.

Fungi↗
PubMed2002

[Profuse scabies: kinetic curves of parasitologic cure with an association of benzyl benzoate and sulfiram].

BACKGROUND: In vitro exposure to benzyl benzoate (25 p. 100) kills Sarcoptes scabiei within three hours. The aim of our study was to determine in vivo elimination of Sarcopte scabiei with a benzyl benzoate-sulfiram association. METHODS: Medical charts of patients hospitalized for disseminated scabies from 1993 to 1999 were reviewed retrospectively. The diagnosis of scabies was confirmed by microscopic determination. Parasitological examinations were conducted every day or every two days until negative results. Patients were treated by successive applications of benzyl benzoate until parasitological cure. RESULTS: Twenty patients were included in the study. The median delay of parasitological cure was seven days. After 15 days, 95 p. 100 of patients were cured. Two cutaneous side-effects were reported. DISCUSSION: Despite immediate in vitro efficacy, benzyl benzoate action is delayed in vivo. The time of parasitological negativation after one application of benzyl benzoate is unknown. Therefore, it is not currently possible to determine whether our therapeutic regimen was excessive or not.

Aged↗
PubMed2000

Pharmacological profile of SL 59.1227, a novel inhibitor of the sodium/hydrogen exchanger.

1. The NHE1 isoform of the Na(+)/H(+) exchanger plays an important role in the regulation of intracellular pH and in cardiac cell injury caused by ischaemia and reperfusion. SL 59.1227 is a novel imidazolypiperidine Na(+)/H(+) antiport inhibitor which is structurally unrelated to previously described acylguanidine inhibitors such as cariporide. 2. Recovery of pH(i) following an intracellular acid load was measured in CCL39-derived PS120 variant cells, selectively expressing either NHE1 or NHE2 isoforms of the Na(+)/H(+) exchanger. pH(i) recovery was potently and selectively slowed by SL 59.1227 in NHE1-expressing cells (IC(50) 3.3+/-1.3 nM) versus NHE2-expressing cells (2.3+/-1.0 microM). The respective IC(50) values for cariporide were 103+/-28 nM (NHE1) and 73+/-46 microM (NHE2). 3. In anaesthetized rats following left coronary artery occlusion (7 min) and reperfusion (10 min) SL 59.1227 (10 - 100 microg kg(-1) min(-1) i.v.) inhibited ischaemia-mediated ventricular tachycardia (71 - 100%) and reperfusion-induced ventricular fibrillation (75 - 87%) and prevented mortality. Bolus i.v. administration of SL 59.1227 (1 mg kg(-1)) produced anti-arrhythmic effects when administered either before or during ischaemia. 4. Cardiac infarct size was determined in anaesthetized rabbits following left coronary artery occlusion (30 min) and reperfusion (120 min). Infarct size measured as a percentage of the area at risk was 36.2+/-3.4% (control group) versus 15.3+/-3.9% (SL 59.1227 0.6 mg kg(-1) i.v.). 5. SL 59.1227 is the first example of a potent and NHE1-selective non-acylguanidine Na(+)/H(+) exchanger inhibitor. It possesses marked cardioprotective properties.

Animals↗
PubMed1998

[Tinea capitis in Creteil. Trends over ten years].

INTRODUCTION: We analyzed tinea capitis data in a Paris suburban area over a 11-year period from (1985-1995) to evaluate epidemiology trends. PATIENTS AND METHODS: The following data were collected for patients seen at the Créteil myco-dermatology clinic with cultures positive for tinea capitis: sex, age, ethnic origin, fungal culture. RESULTS: Tinea capitis was observed in 336 cases (56 p. 100 females). Eight percent of the patients were under the age of 10 years and 11 p. 100 over 20 years. Trichophyton soudanense was isolated in 45 p. 100 of the patients. Anthropophilic agents rose over the 10 year period while the number of zoophilic agents remained stable. Specific dermatophytes appeared to predominate in populations of different ethnic origin. There was a two-fold increase in the number of tinea capitis cases in the 1990-1995 period compared with the five previous years. DISCUSSION: The percentage of adults with tinea capitis (11 p. 100) is higher than the 5 p. 100 reported in the literature. The rise in the number of anthropophilic tinea capitis cases resulted from an increase in T. soudanense (originating in Africa), probably related to the increasing immigrant population. This agent was identified in 95 p. 100 of the patients of African origin. Differing lifestyles and transmission between school children makes it quite difficult to interpret the correlation between ethnic origin and specific dermatophytes.

Adult↗
PubMed1997

Tinea capitis in adults: misdiagnosis or reappearance?

BACKGROUND: According to the literature, tinea capitis in adults is supposed to be rare; we have recently observed a significant increase in cases. METHODS: Epidemiological, clinical and mycological features were studied in all adult tinea capitis diagnosed over 1 year in our department. RESULTS: Eight cases were observed: 75% of them were women, 50% never traveled and 62.5% had an underlying immunosuppressive disease. Scalp scaling and alopecia were the most frequent clinical features. A zoophilic dermatophyte was recovered in 50% of cases. CONCLUSION: These cases represent 11% of all tinea capitis observed in the same period of time (higher than the 3-5% observed in the literature). Secretion of sebum and colonization by Pityrosporon orbiculare are supported to protect the scalp against dermatophytic invasion after puberty, but an immune defect may also facilitate hair invasion. The erroneous notion of the disease being uncommon and the frequent atypical clinical presentation require a high degree of clinical suspicion.

Adult↗
PubMed1995

Plasmodium falciparum: detection of P-glycoprotein in chloroquine-susceptible and chloroquine-resistant clones and isolates.

Recent studies have suggested the potential involvement of multidrug resistance (mdr) genes in resistance to quinoline-containing compounds in Plasmodium falciparum parasites. Three different antibodies were used to detect the malarial mdr 1 protein product by indirect immunofluorescence and/or immunoblot in fresh clinical isolates and clones of P. falciparum from different geographic origins. A 160-kDa protein was detected in all five parasite clones by immunoblot and around the food vacuole by IFA, regardless of the level of sensitivity to chloroquine and the modulation by desipramine of chloroquine accumulation. Our results suggest that chloroquine resistance is not correlated with the presence of the Pfmdr1 product.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Histone-poly(A) hybrid molecules as tools to block nuclear pores.

Histone-poly(A) hybrid molecules were used for transport experiments with resealed nuclear envelopes and after attachment of a cleavable cross-linker (SASD) to identify nuclear proteins. In contrast to histones, the hybrid molecules cannot be accumulated in resealed nuclear envelopes, and in contrast to poly(A), the export of hybrids from preloaded nuclear envelopes is completely impaired. The experiments strongly confirm the existence of poly(A) as an export signal in mRNA which counteracts the nuclear location signals (NLS) in histones. The contradicting transport signals in the hybrid molecules impair translocation through the nuclear pore complex. The failure to accumulate hybrid molecules into resealed nuclear envelopes results from the covalent attachment of polyadenylic acid to histones in a strict 1:1 molar ratio. This was demonstrated in control transport experiments where radiolabeled histones were simply mixed with nonlabeled poly(A) or radiolabeled poly(A) mixed with nonlabeled histones. In comparison, control uptake experiments with histones covalently linked to a single UMP-mononucleotide are strongly enhanced. Such controls exclude the conceivable possibility of a simple masking of the nuclear location signal in the histones by the covalent attached poly(A) moiety. Photoreactive histone-poly(A) hybrid analogs serve to identify nuclear envelope proteins--presumably in the nuclear pore--with molecular weights of 110, 80, and 71.4 kDa.

Animals↗
PubMed1994

Haloallylamine inhibitors of MAO and SSAO and their therapeutic potential.

Based on mechanistic understandings, molecular modeling and extensive quantitative structure-activity relationships, appropriately substituted haloallylamine derivatives were designed as potential mechanism-based inhibitors of MAO and/or SSAO. Potent inhibition of MAO-B and SSAO occurred with fluoroallylamines whereas chloroallylamines, such as MDL 72274A ((E)-2-phenyl-3-chloroallylamine hydrochloride), were selective and potent inhibitors of SSAO. MDL 72974A (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride is a potent (IC50 = 10(-9) M) inhibitor of both MAO-B and SSAO, with 190-fold lower affinity for MAO-A. In clinical studies, oral doses as low as 100 micrograms produced substantial inhibition of platelet MAO-B. Essentially complete inhibition occurred at 1 mg with the effect lasting 6-10 days. One or 4 mg MDL 72974A given daily for 28 days to 40 Parkinson's patients treated with L-dopa produced statistically significant reductions in the Unified Parkinson's Disease Rating Scale. MAO-B inhibitors, such as MDL 72974A and L-deprenyl, offer the potential of being neuroprotective in Parkinson's Disease and other neurogenerative disorders. Concommitant inhibition of SSAO may provide additional, but as yet unproven, advantages over pure inhibitors of MAO-B.

Allyl Compounds↗
PubMed1993

MDL 72,974A: a selective MAO-B inhibitor with potential for treatment of Parkinson's disease.

MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine, hydrochloride] was designed to be a selective, mechanism-based irreversible inhibitor of monoamine oxidase type B (MAO-B). The compound is a potent, selective MAO-B inhibitor in vitro and in vivo. In vitro studies revealed an IC50 value (MAO-B) of 3.6 nM with 189-fold selectivity compared to MAO-A. In rats, profound inhibition of MAO-B was achieved after a single oral dose with an ED50 of 0.18 mg/kg; a dose 44 times this amount was required to inhibit MAO-A by 50%. Selectivity was maintained following chronic dosing. MDL 72,974A had minimal sympathomimetic effects and did not potentiate the cardiovascular effects of tyramine, even at 50 times the MAO-B inhibiting dose. This inhibitor was equally effective and well-tolerated in man. In human volunteers, potent inhibition of platelet MAO-B activity was observed at submilligram doses (ED50 = 90 micrograms) following a single oral dose. Upon multiple oral doses of 100 micrograms, as much as 80% of MAO-B could be inhibited. In phase II studies, MDL 72,974A is proving to be a useful adjunct to conventional therapy. Patients (250) with Parkinson's disease, treated once daily with either 1 or 4 mg, together with L-Dopa and a decarboxylase inhibitor (MadoparR or SinemetR), saw significant improvements in symptoms compared with those on standard therapy without the inhibitor.

Allyl Compounds↗
PubMed1992

Covalent attachment of ribonucleic acids to proteins.

As a prerequisite for the synthesis of affinity labels, we describe methods to couple histones to ribonucleic acids. For the synthesis of these covalent hybrid molecules, we used a population of histones H1, H2A, H2B, H3, and H4 from calf thymus and polyadenylic acid with an average chain length of up to 260-280 bases, representing the size of poly(A)-tails from mature mRNAs. Three methods were investigated. (a) Poly(A) containing an 8-N3-A residue was cross-linked to histones by ultraviolet irradiation. (b) The 3'-end of the polynucleotide was connected to a mononucleotide containing an aliphatic amino group, and the resulting poly(A)-derivative was coupled to histones via derivation with a bromoacetyl group. (c) The 3'-end of the polynucleotide was oxidized with sodium periodate and bound covalently to an amino group of the polypeptide. To demonstrate the RNA content of the hybrid molecule, the poly(A) was removed with RNase T2.

Animals↗
PubMed1992

[Contribution of molecular genetics to the understanding of chemoresistance of Plasmodium falciparum].

Resistance to pyrimethamine and proguanil is due to a single point mutation in the gene that codes for dihydrofolate reductase. A single mutation gives rise to resistance to only one of the drugs. Resistance to both drugs results from several mutations. Chloroquine resistance phenotype is due to a rapid efflux of the drug from the parasite's digestive vacuole. This efflux is associated with a transmembrane permeability glycoprotein, or P-gp, which is similar to the protein implicated in the multidrug resistant phenotype of some cancer cells. However, one or several other poorly understood major gene(s) may be involved. Drugs which can inhibit the supposed affinity of P-gp for chloroquine are under study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Piroximone, dobutamine and nitroprusside: comparative effects on haemodynamics in patients with congestive heart failure.

Four intravenous doses of piroximone, an imidazolone derivative, were administered to 12 patients with congestive heart failure to produce a four-point dose-response curve. The haemodynamic effects were compared with those of dobutamine and nitroprusside, the substances being given sequentially and in randomized order. Piroximone and dobutamine significantly and similarly increased cardiac index (CI) and stroke volume index (SVI). Nitroprusside produced no such effect. By contrast, piroximone and nitroprusside significantly and similarly decreased mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP) and pulmonary vascular resistance (PVR), while such changes were not seen following dobutamine. Direct comparisons between the agents were made at doses that lowered systemic vascular resistance (SVR) to the same extent. The major difference between dobutamine and piroximone was an apparent additional vasodilator activity displayed by piroximone as demonstrated by a significantly greater decrease in MPAP, PCWP and RAP for a matched reduction in SVR and a similar increase in CI. The major difference between nitroprusside and piroximone was the significantly higher increase in CI and SVI elicited by piroximone for a matched reduction in SVR and a similar decrease in PCWP and RAP. The changes in loading conditions being equivalent, the higher increase in CI is likely to be accounted for by a direct inotropic activity.

Adult↗