PubMed Health⌕ Search

Biomedical subjects

B Leclerc

Publications and source records attributed to B Leclerc.

14 recordsLinked to original sources
PubMed2006

Development of a real-time (Q) PCR assay to measure variation in expression of prolactin receptor mRNA in the hypothalamus and pituitary gland during late embryogenesis in turkeys and chickens.

Changes in levels of PRLR mRNA in the pituitary gland and hypothalamus of chickens and turkeys from embryonic day (ED) 15 and ED21 to 1 day post-hatch, respectively, were measured by real-time PCR. In both species, PRLR mRNA increased from low levels during the last week of ED to reach maxima at the peri-hatch period. Similarly, circulating levels of PRL also increased during this interval and were highly correlated with levels of the PRLR mRNA in both the pituitary gland and hypothalamus. This suggests that PRL was up-regulating its receptor. In support of this, stimulation of the turkey pituitary gland with VIP on ED24 resulted in a 4- and 3-fold increase in PRL and PRLR, respectively. Since VIP had no direct effect on the levels of PRLR transcript in the hypothalamus, it is likely that VIP is acting indirectly through increased PRL to up-regulate the number of receptors.

Animals↗
PubMed2006

Investigation and modelling approach of the mechanical properties of compacts made with binary mixtures of pharmaceutical excipients.

Three pharmaceutical excipients (microcrystalline cellulose, lactose, anhydrous calcium phosphate) and their binary mixtures were compacted to form compacts of various mean porosities. Some mechanical properties (Young's modulus, tensile strength and Brinell hardness) were studied on these compacts. The mechanical properties of the binary mixtures were not proportional to the mixture composition expressed in mass. More, for all the properties, a negative deviation was always observed from this linear relationship. In reference to a composition percolation phenomenon, critical mass fractions were detected from the graph mechanical property vs. mass composition of a mixture. The results obtained with Brinell hardness differed from the results of the Young's modulus and the tensile strength, i.e. the most plastic material in the binary mixture controlled the mixture behaviour. Secondly, a predictive model based on a statistical approach was proposed for the Young's modulus and the tensile strength. The validity of this model was verified on experimental data, and an interaction parameter used to characterize the affinity of the two compounds was calculated. Finally, the X-ray tomography technique was applied to the compacts of cellulose/phosphate mixtures to obtain cross-sections images of the compacts. The analysis of the cross-sections images allowed explaining the no linear relationship of the different mechanical properties results observed on these binary mixtures.

Cellulose↗
PubMed2006

Compaction behaviour and new predictive approach to the compressibility of binary mixtures of pharmaceutical excipients.

The compressibility of three pharmaceutical excipients (microcrystalline cellulose, lactose and anhydrous calcium phosphate) and their binary mixtures was studied. The aim of this work was to observe the impact of the mass composition of the mixture on the compressibility. The single-compound materials and their mixtures were compacted using instrumented presses. It allowed obtaining compression cycles (i.e., force-displacement curves) which were associated with energy measurements (specific compaction energy, Esp cp and specific expansion energy, Esp exp). It was observed that for the mixtures studied, the change of Esp cp with the mass composition could be fitted using a linear relationship (it was not the case with Esp exp). A linear relationship between the porosity of mixture's compacts and the mass composition was also obtained. Heckel's plots were then obtained for the three excipients and the mixtures. The mean yield pressure was calculated with the "in-die-method" and the "out-of-die method". A proportional relationship was not valid for the mean yield pressures. But, a predictive approach was proposed in order to obtain indirectly the mean yield pressure of a binary mixture if the data of the single materials were known. It used the linear mixing rule observed with the porosity. The validity was verified and compared with the experimental values. This comparison showed that it was possible to predict the mean yield pressure of binary mixtures from the accessible data of the single excipients.

Calcium Phosphates↗
PubMed2004

Compaction of crystallographic forms of pharmaceutical granular lactoses. I. Compressibility.

Physico-chemical properties of a substance including the compaction behaviour are directly connected with the crystalline structure. The aim of this work is to compare the compaction behaviour in a group of excipient and in this first part, to display the influence of lactose structures on the compressibility. alpha-Lactose monohydrate (LalphaM), anhydrous beta-lactose (LbetaA), anhydrous alpha-lactose (LalphaA) and partly amorphous lactose (FF) were compressed using instrumented presses to investigate the densification behaviour under pressure. Force-displacement curves were associated to two energy parameters, specific cycle energy and specific expansion energy. This approach was used to class the four lactose species. It is possible to differentiate three groups with the specific energy cycle, FF, LalphaA/LbetaA and LalphaM in decreasing order of this energy. At the same time, the values of specific expansion energy are relatively low for FF and LalphaA contrary to LalphaM and LbetaA. Then, Heckel's plots were obtained with two compact geometries and the mean yield pressure was calculated from the in-die-method and the out-of-die-method. Two lactoses seem to differ, LalphaM appears to be the most ductile whereas LalphaA is more brittle than the others. Finally, it is concluded, that in the case of lactoses, pseudopolymorphism seems to affect the compressibility more than anomerisation or partial amorphisation.

Compressive Strength↗
PubMed2001

Magnetic resonance imaging investigation of the mixing-segregation process in a pharmaceutical blender.

Magnetic Resonance Imaging (MRI) was used to study the mixing process of binary mixtures of free flowing sugar beads in a Turbula mixer. In order to make particles MRI-sensitive, some reference beads were doped with an organic oil. Doped and undoped particles were mixed and MRI was used to non-destructively image the particle bed for a given number of mixer rotations (NR), bead diameter ratio (R=d(ref)/d(i)) and rotation speed (V). All the results were quantified on the basis of image analysis to characterise the degree of mixing. Studies showed that for binary mixtures of identical particle size, the mixing was complete after 30 rotations, whereas for beads of different size (R=2.8) a segregated steady state was obtained after nearly 10 rotations. Experiments revealed that segregation appeared as soon as R=0.9. Moreover, the lower the rotation speed, the more segregated the final state was. It appeared that for a filling level greater than 80%, dead regions appeared in the centre of the powder bed. In conclusion, when the particles are non-cohesive, the Turbula blender perfectly mixes identical beads but segregation occurs for beads of different size after just a few rotations.

Carbohydrates↗
PubMed2001

Antipyretic efficacy of an initial 30-mg/kg loading dose of acetaminophen versus a 15-mg/kg maintenance dose.

OBJECTIVE: To compare the antipyretic efficacy of an initial 30-mg/kg acetaminophen loading dose versus a 15-mg/kg maintenance dose. METHODS: A double-blind, parallel-group, randomized clinical trial was conducted. A total of 121 febrile (rectal temperature between 39 degrees C and 40 degrees C) but otherwise healthy outpatients who were 4 months to 9 years of age and weighed 4 to 26 kg were assigned randomly to 1 of the dose groups: 15 mg/kg (n = 62) and 30 mg/kg (n = 59). RESULTS: In an "intention to treat" analysis, the time to obtain a temperature lower than 38.5 degrees C was significantly shorter in the 30-mg/kg than in the 15-mg/kg group (110 +/- 94 minutes vs 139 +/- 113 minutes). The maximum temperature decrease was significantly higher in the 30-mg/kg than in the 15-mg/kg group (2.3 +/- 0.7 degrees C vs 1.7 +/- 0.6 degrees C). Duration of rectal temperature below 38.5 degrees C was significantly longer in the 30-mg/kg than in the 15-mg/kg group (250 +/- 92 minutes vs 185 +/- 121 minutes, respectively). Adverse events were reported in 6 children in the 30-mg/kg group compared with 5 in the 15-mg/kg group (hyperthermia, hypothermia, vomiting). The difference was not statistically significant. CONCLUSION: An initial 30-mg/kg acetaminophen loading dose seemed to be more effective in reducing fever than a 15-mg/kg maintenance dose. No difference was observed regarding clinical tolerance. These data suggest that acetaminophen treatment of fever may be more efficient in an initial loading dose.

Acetaminophen↗
PubMed2000

Release of mifepristone from biodegradable matrices: experimental and theoretical evaluations.

Diffusion of mifepristone in poly [(D,L) lactide-co-glycolide)] films was studied by release experiments. Five 50/50 copolymers of increasing molecular weights were used. The degradation effects were shown by gel permeation chromatography (GPC). Release kinetics show the effect of copolymer molecular weights on diffusion and degradation properties of loaded films. A new theoretical model for drug release from a biodegradable matrix was proposed with two assumptions: correlation of the diffusion coefficient with the polymer molecular weight and existence of a first order degradation kinetic. Higuchi's equation is verified at early time and the diffusion coefficient in the non-degraded polymer can be measured. The degradation constant is determined at long time and is compared with the results of GPC.

Algorithms↗
PubMed2000

Comparison of additive trees using circular orders.

It has been postulated that existing species have been linked in the past in a way that can be described using an additive tree structure. Any such tree structure reflecting species relationships is associated with a matrix of distances between the species considered which is called a distance matrix or a tree metric matrix. A circular order of elements of X corresponds to a circular (clockwise) scanning of the subset X of vertices of a tree drawn on a plane. This paper describes an optimal algorithm using circular orders to compare the topology of two trees given by their distance matrices. This algorithm allows us to compute the Robinson and Foulds topologic distance between two trees. It employs circular order tree reconstruction to compute an ordered bipartition table of the tree edges for both given distance matrices. These bipartition tables are then compared to determine the Robinson and Foulds topologic distance, known to be an important criterion of tree similarity. The described algorithm has optimal time complexity, requiring O(n(2)) time when performed on two n x n distance matrices. It can be generalized to get another optimal algorithm, which enables the strict consensus tree of k unrooted trees, given their distance matrices, to be constructed in O(kn(2)) time.

Algorithms↗
PubMed1999

Rheological characterization of pharmaceutical powders using tap testing, shear cell and mercury porosimeter.

Most of the pharmaceutical processes involved in the manufacturing of so lid dosage forms are connected with powder flow properties, at least for some of the intermediate steps. Powder flow characteristics are commonl y investigated by various measurements, such as handling angles, tap tes ting, shear cell measurements, etc. All these approaches allow the calc ulation of indices characterising powder flowability. Unfortunately, th ese methodologies are highly product consuming, which is a limitation in the first steps of a novel drug development, when only a small amount of product is available. The use of mercury porosimetry to evaluate compre ssibility and flow properties of powders could be a new and alternative approach to obtain insight in the rheological properties of granular med ium by the interpretation of the first part of programs (low pressures) . We have developed such an evaluation and compared the results obtaine d with those given by tap testing and shear cell measurements, applied t o four excipients for direct tabletting and three different drugs. Merc ury porosimetry turned out to be a sensitive technique, able to providequantitative information about powder flow properties, complemen ted by an evaluation of particles micro porosity and size distribution, in a single step. These characterisations are obtained with only approx imately 250mg of bulk powder compared to high quantities ( >100g) needed for other methods.

Powders↗
PubMed1994

A single mutation of the fumarylacetoacetate hydrolase gene in French Canadians with hereditary tyrosinemia type I.

BACKGROUND: Hereditary tyrosinemia type I is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. The disorder clusters in the Saguenay-Lac-St.-Jean area of Quebec. In this region, 1 of 1846 newborns is affected and 1 of every 22 persons is thought to be a carrier. Recently, we identified a splice mutation and two nonsense mutations in the fumarylacetoacetate hydrolase gene in two patients from Quebec with tyrosinemia type I. METHODS: We used allele-specific-oligonucleotide hybridization to examine the frequency of these three candidate mutations in patients with tyrosinemia type I and in the population of Quebec. RESULTS: The splice mutation was found in 100 percent of patients from the Saguenay-Lac-St.-Jean area and in 28 percent of patients from other regions of the world. Of 25 patients from the Saguenay-Lac-St.-Jean region, 20 (80 percent) were homozygous for this mutation, a guanine-to-adenine change in the splice-donor sequence in intron 12 of the gene, indicating that it causes most cases of tyrosinemia type I in the region. The frequency of carrier status, based on screening of blood spots from newborns, was about 1 per 25 in the Saguenay-Lac-St.-Jean population and about 1 per 66 overall in Quebec. CONCLUSIONS: This study identified the most prevalent mutation causing hereditary tyrosinemia in French Canada; it also showed the feasibility of DNA-based testing for carriers in the population at risk.

Alleles↗
PubMed1994

Identification of a stop mutation in five Finnish patients suffering from hereditary tyrosinemia type I.

Hereditary tyrosinemia type I is a metabolic disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH, EC 3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. The molecular basis of FAH deficiency was examined in five Finnish patients suffering from this severe metabolic disease. No immunoreactive FAH nor enzymatic activity were found in their liver. Direct sequencing of the 14 exons of the FAH gene showed a G to A transition, which predicts a change from tryptophan to a stop codon (TGG-->TGA) at position 262 (W262X). Four of the five patients examined were homozygous for the mutation. Allele specific oligonucleotide hybridization showed a predominance of the W262X mutation in Finland (9 of 10 alleles) and the absence of this mutant allele in patients from other parts of the world. The loss of a BsaJI restriction site in those patients may be used for diagnosis.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity.

Hereditary tyrosinemia type 1 is an autosomal recessive disease caused by a deficiency of the last enzyme in the catabolic pathway of tyrosine, fumarylacetoacetate hydrolase (FAH). To analyze the mutations involved in this disease, and as a first step towards elucidating the mechanisms regulating the transcription of the FAH gene, we have isolated and characterized the human gene coding for FAH. The gene contains 14 exons and spans approximately 35 kilobases of DNA. The 5' end of the gene is highly GC-rich, and eleven putative binding sites for the transcription factor Sp 1 were identified in the proximal region of the promoter. We investigated the molecular basis of FAH deficiency in a hereditary tyrosinemia type 1 patient whose liver FAH showed a very low enzymatic activity. Sequencing of the liver FAH cDNA of the patient revealed a C to A transversion in the FAH mRNA, which predicted the replacement of an alanine (A) residue with an aspartic acid (D) residue at position 134 (A134D) of the amino acid sequence of the corresponding protein. Direct sequencing of genomic DNA indicated that the patient was heterozygous for the A134D mutation. The allele that does not carry the A134D mutation was expressed at a very low level in the liver of the patient. Expression of the mutant allele in CV-1 cells confirmed that the A134D mutation was responsible for the lack of enzymatic activity in the liver of the patient.

Alleles↗