[Palmar fasciitis after carboplatin administration for an ovarian adenocarcinoma].
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Aged↗
Biomedical subjects
C Andrès
Publications and source records attributed to C Andrès.
Comparative study of the lubricant performance of Compritol 888 ATO either used by blending or by hot melt coating.
Compritol 888 ATO is used as a lubricant in oral solid dosage formulations. It can also be used as a hot melt coating agent sprayed onto a powder. In this study, we compare the lubricant performance of Compritol 888 ATO either used by classical blending or by hot melt coating onto Lactopress by compression tests. In physical mix, the Compritol concentration does not affect the compressibility. The same compressibility is obtained with lactose coated by 0.5 or 1% of Compritol, but a higher compressibility can be observed with 2 and 3%. Cohesiveness of lactose depends on the process: hot melt coating induces a decrease of tablet tensile strength. In terms of forces transmission during compression phase and axial ejection pressures, Compritol used by hot melt coating allows for a concentration of 0.5% to directly obtain the lubricant performance of 3% of Compritol used by blending. These results suggest that the hot melt coating process induces an homogeneous repartition of the lubricant on the lactose surface, contrary to classical blending procedure. Thus, lubrication by hot melt coating seems to be a very efficient procedure. It could be used specifically for large surface area particulate systems producing a lot of friction.
Administration, Oral↗
Comparative study of the lubricant performance of Compritol HD5 ATO and Compritol 888 ATO: effect of polyethylene glycol behenate on lubricant capacity.
The aim of this paper is to study the lubricant capacity of Compritol HD5 ATO, a glyceryl and polyethylene glycol dibehenate, obtained by atomization. This material is compared to Compritol 888 ATO, constituted only by glyceryl dibehenate. First, this study verifies that Compritol HD5 ATO and Compritol 888 ATO present the same granular characteristics and that their mixes with Lactopress present no structural differences. Secondly, in term of compressibility and cohesiveness, the use of Compritol 888 ATO or Compritol HD5 ATO with Lactopress does not involve any significant modification. Finally, the minor difference of lubricant capacity between Compritol HD5 ATO and Compritol 888 ATO has no consequence in compression practice. The presence of polyethylene glycol behenate does not decrease the glyceryl dibehenate compression functionality. This study concludes that Compritol HD5 ATO could be a very interesting excipient because it associates the glyceryl dibehenate lubricant capacity with the polyethylene glycol behenate-specific capacity in terms of dissolution enhancement.
Chemistry, Pharmaceutical↗
Affinity scale between a carrier and a drug in DPI studied by atomic force microscopy.
The dry powder inhalers (DPIs) consist, in the most cases, of ordered mixture where the particles adhesion results of interactions between the drug and the carrier. Generally, one step of production process is the micronization of the drug particles in order to reduce the size for ordered mixing optimization. But this operation is known to partially create an amorphous surface. In this case, surrounding storage conditions, like relative humidity (RH), are able to modify the percentage of amorphous drug surface. The aim of this study was to investigate surface reactivity, surface energy and direct force measurements by atomic force microscopy (AFM) between lactose (carrier) and zanamivir (drug) crystals references in various conditions of RH. Secondly, an amorphization of the drug surface was induced by humidity relative treatment in order to evaluate the consequences of the transition from crystal to amorphous phase. The study demonstrated that the amorphization of drug surface induces an increase of drug affinity with the carrier surface. Ex situ and in situ amorphization of zanamivir tend to reach the affinity measured between raw materials: carrier and micronized drug particles. AFM allowed adhesion force discrimination between the different forms of the drug particles and demonstrated the potential for investigating adhesion properties in DPI formulation.
Drug Carriers↗
Dry powder inhaler: influence of humidity on topology and adhesion studied by AFM.
In the dry powder inhalers (DPIs), the adhesion results of the interactions between the active substance and the excipient. The carrier and the micronized drug particle morphologies are believed to affect the delivery of the drug. In this work, the couple studied was the lactose monohydrate and micronized zanamivir, used for the treatment of influenza. In a first approach, observations by scanning electron microscopy (SEM) have shown that the relative humidity (RH) greatly influenced the zanamivir amount fixed on the lactose monohydrate surface. This paper deals with the direct measurement in controlled atmosphere by atomic force microscopy (AFM) of the forces and the interaction ranges between a zanamivir probe and a lactose substrate. Selected zanamivir crystals were attached to the standard AFM probe. Different RH have been used in order to determine influent parameters permitting to identify the nature of adhesion forces between them. This study demonstrated that the increase of RH modified progressively the surface topology of the two components and increased the adhesion force.
Aerosols↗
On the difficulty of assessing the specific surface area of magnesium stearate.
The water content of as-received commercial magnesium stearate batches from animal and vegetable sources have been modified by ageing in humid air at room temperature or by vacuum treatment. The complete adsorption-desorption isotherms of nitrogen and krypton vapours by samples of these as received and modified materials have been measured at liquid nitrogen temperature after standardised vacuum degassing. They are greatly affected by the initial water content of the material. In particular: (a) the BET surface area values computed from the adsorption branch vary widely and is increasing with increasing water content; (b) anomalous hysteresis of varying amplitude is observed in all cases except adsorption of krypton on the material with the lowest water content; (c) the hysteresis loops extend down to very low desorption pressure values and cannot be accounted for by capillary condensation. Lastly, the surface area value of a given material computed from nitrogen and krypton adsorption may differ by a factor as high as six. Accordingly, the very significance of BET surface area values obtained from routine adsorption experiments should be regarded as questionable, at least until the mechanisms of adsorption are fully clarified.
Adsorption↗
MECP2 is highly mutated in X-linked mental retardation.
Following the recent discovery that the methyl-CpG binding protein 2 (MECP2) gene located on Xq28 is involved in Rett syndrome (RTT), a wild spectrum of phenotypes, including mental handicap, has been shown to be associated with mutations in MECP2. These findings, with the compelling genetic evidence suggesting the presence in Xq28 of additional genes besides RabGDI1 and FMR2 involved in non-specific X-linked mental retardation (MRX), prompted us to investigate MECP2 in MRX families. Two novel mutations, not found in RTT, were identified. The first mutation, an E137G, was identified in the MRX16 family, and the second, R167W, was identified in a new mental retardation (MR) family shown to be linked to Xq28. In view of these data, we screened MECP2 in a cohort of 185 patients found negative for the expansions across the FRAXA CGG repeat and reported the identification of mutations in four sporadic cases of MR. One of the mutations, A140V, which we found in two patients, has been described previously, whereas the two others, P399L and R453Q, are novel mutations. In addition to the results demonstrating the involvement of MECP2 in MRX, this study shows that the frequency of mutations in MECP2 in the mentally retarded population screened for the fragile X syndrome is comparable to the frequency of the CGG expansions in FMR1. Therefore, implementation of systematic screening of MECP2 in MR patients should result in significant progress in the field of molecular diagnosis and genetic counseling of mental handicap.
Adult↗
Plasma fatty acid levels in autistic children.
Phospholipid fatty acids are major structural components of neuronal cell membranes, which modulate membrane fluidity and hence function. Evidence from clinical and biochemical sources have indicated changes in the metabolism of fatty acids in several psychiatric disorders. We examined the phospholipid fatty acids in the plasma of a population of autistic subjects compared to mentally retarded controls. Our results showed a marked reduction in the levels of 22: 6n-3 (23%) in the autistic subjects, resulting in significantly lower levels of total (n-3) polyunsaturated fatty acids (PUFA) (20%), without significant reduction in the (n-6) PUFA series, and consequently a significant increase in the (n-6)/(n-3) ratio (25%). These variations are discussed in terms of potential differences in PUFA dietary intake, metabolism, or incorporation into cellular membranes between the two groups of subjects. These results open up interesting perspectives for the investigation of new biological indices in autism. Moreover, this might have new therapeutic implications in terms of child nutrition.
Adolescent↗
Preformulation: effect of moisture content on microcrystalline cellulose (Avicel PH-302) and its consequences on packing performances.
This study evaluates the influence of moisture content on the packing performances of a new grade of microcrystalline cellulose (MCC) (Avicel PH-302) either by classical method or by an unconventional compression technique (constant volume reduction of powder bed). An increase in moisture content decreases the apparent density of the powder bed, resulting from interparticulate friction enhancement. This modification of apparent density seems to be the main effect caused by the presence of humidity, which explains the variations of compression properties, like an increase of powder plasticity generally observed in the experimental conditions.
Cellulose↗
Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen.
Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.
Antibodies, Monoclonal↗
Epitope mapping of 53 antibodies against prostate-specific antigen.
A panel of 53 antibodies from the ISOBM TD-3 PSA Workshop were tested for reactivity with iodinated derivatives of free PSA or the alpha1-antichymotrypsin PSA complex using the BIAcore system. Two antibodies (#69 and #83) showed low binding (<8%) for both antigens. One group of antibodies (#25, #26, #33, #54, #68, #73, #77, #78 and #91) had a much lower affinity for the complex (<12%) than for the free antigen (>65%). According to the mapping study, it was possible to categorize the antibodies into 29 different groups. Four antibodies were not classified. The two-dimensional representation of all interactions between the antibodies showed a complex network on the PSA molecule. Antibodies with lower affinity for the complex than for the free PSA appeared to bind epitopes in a common region, and thus it was not possible to perform sandwich assays with antibodies specific for free PSA.
Antibodies↗
Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study.
OBJECTIVE: To investigate the relation between decreased maternal food intake and risk factors for coronary heart disease in adult life. DESIGN: Cross sectional study. SUBJECTS: 169 subjects exposed to malnutrition in utero (intrauterine group) during the siege of Leningrad (now St Petersburg) in 1941-4; 192 subjects born in Leningrad just before rationing began, before the siege (infant group); and 188 subjects born concurrently with the first two groups but outside the area of the siege (unexposed group). SETTING: Ott Institute of Obstetrics and Gynaecology, St Petersburg. MAIN OUTCOME MEASURES: Development of risk factors for coronary heart disease and diabetes mellitus-obesity, blood pressure, glucose tolerance, insulin concentrations, lipids, albumin excretion rate, and clotting factors. RESULTS: There was no difference between the subjects exposed to starvation in utero and those starved during infant life in: (a) glucose tolerance (mean fasting glucose: intrauterine group 5.2 (95% confidence interval 5.1 to 5.3), infant group 5.3 (5.1 to 5.5), P = 0.94; mean 2 hour glucose: intrauterine group 6.1 (5.8 to 6.4), infant group 6.0 (5.7 to 6.3), P = 0.99); (b) insulin concentration; (c) blood pressure; (d) lipid concentration; or (e) coagulation factors. Concentrations of von Willebrand factor were raised in the intrauterine group (156.5 (79.1 to 309.5)) compared with the infant group (127.6 (63.9 to 254.8); P < 0.001), and female subjects in the intrauterine group had a stronger interaction between obesity and both systolic (P = 0.01) and diastolic (P = 0.04) blood pressure than in the infant group. Short adult stature was associated with raised concentrations of glucose and insulin 2 hours after a glucose load-independently of siege exposure. Subjects in the unexposed group had non-systematic differences in subscapular to triceps skinfold ratio, diastolic blood pressure, and clotting factors compared with the exposed groups. CONCLUSIONS: Intrauterine malnutrition was not associated with glucose intolerance, dyslipidaemia, hypertension, or cardiovascular disease in adulthood. Subjects exposed to malnutrition showed evidence of endothelial dysfunction and a stronger influence of obesity on blood pressure.
Birth Weight↗
Study of morphology of reactive dissolution interface using fractal geometry.
The determination of reactive fractal dimension was carried out using two forms of the Noyes-Whitney equation, -dQ/dt = K(Q/Q0)DR/3 and -dQ/dt = K'RDR-3 using the Richardson plot on the basis of previous data obtained by dissolution of an orthoboric acid powder. The correlation of the results provided by the two ways of calculation allows proposal of the hypothesis that dissolution begins on a specific population of reactive sites and probably promotes the formation of microporous volumes or cracks.
Microscopy, Electron, Scanning↗
The insertion allele of the ACE gene I/D polymorphism. A candidate gene for insulin resistance?
BACKGROUND: The insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased coronary heart disease (CHD), although the mechanism of this association is not apparent. We tested the hypothesis that the deletion allele of the ACE gene is associated with insulin resistance. METHODS AND RESULTS: We related ACE genotype to components of the insulin-resistance syndrome in 103 non-insulin-dependent diabetic (NIDDM) and 533 nondiabetic white subjects. NIDDM subjects with the DD genotype had significantly lower levels of specific insulin (DD 38.6, ID 57.1, and II 87.4 pmol.L-1 by ANOVA, P = .011). Non-insulin-treated subjects with the DD genotype had increased insulin sensitivity by HOMA % (DD 56.4%, II 29.4%, P = .027) and lower levels of des 31,32 proinsulin (DD 3.3, II 7.6 pmol.L-1, P = .012) compared with II subjects. There were no differences in prevalence of CHD or levels of blood pressure, serum lipids, or plasminogen activator inhibitor-1 (PAI-1) activity between the three ACE genotypes. In nondiabetic subjects there were no differences in insulin sensitivity, levels of insulin-like molecules, blood pressure, PAI-1, serum lipids, or CHD prevalence between the three ACE genotypes. CONCLUSIONS: We conclude that increased cardiovascular risk of the DD genotype is not mediated through insulin resistance or abnormalities in fibrinolysis. Conversely, we report an increased sensitivity in NIDDM subjects with the ACE DD genotype.
Alleles↗