[Assessment of body composition during pulmonary tuberculosis]. / Évaluation de la composition corporelle au cours de la tuberculose pulmonaire.

BACKGROUND: Although the body mass index (BMI) is the most commonly used tool to assess the nutritional status of patients with active tuberculosis (TB), it does not assess changes in body composition. This study aims to assess the contribution of bioelectrical impedancemetry (BIA) for the assessment of body composition during the course of TB compared to BMI and to examine the associated factors. METHODS: Cross-sectional study carried out in patients with active TB at the pulmonology department of CHU la Rabta in Tunis, Tunisia. The nutritional assessment was based on the measurement of BMI and the analysis of body composition by BIA. Malnutrition was accepted when the lean mass index (LMI) was ≤16kg/m2 in men and 15kg/m2 in women. RESULTS: Ninety-five patients were included. According to their LMI, 38 patients were undernourished. The decline in LMI was associated with the severity of TB. Although BMI and LMI were correlated, the use of BMI alone failed to recognize lean mass loss in one in ten patients. CONCLUSION: Undernutrition is frequent in patients with active TB. It is correlated with the severity of the disease. In addition to anti-tuberculosis drugs, nutritional management of these patients is essential.

Amino-functionalized MCM-41 and MCM-48 for the removal of chromate and arsenate.

The aim of the present work was to investigate the efficiency of three amino-functionalized (hexadecylamine, dodecylamine, and dimethyldodecylamine) mesoporous silicas (MCM-41 and MCM-48) toward the adsorption of arsenate and chromate. Hexadecylamine-functionalized materials were characterized; BET surface areas, pore volumes, and sizes decreased with the functionalization, whereas XRD patterns show that the hexagonal structure of MCM-41 and the cubic structure of MCM-48 were not modified. The zeta potential decreases with pH and the highest arsenate and chromate removal was observed at the lowest pHs. Adsorption of chromium and arsenate was significantly enhanced after functionalization and amino-functionalized MCM-41 adsorb larger amounts of arsenate when compared to expanded MCM-48 materials. Chromate sorption capacities increased with the chain length and the larger capacities were obtained with hexadecylamine-functionalized mesoporous silicas. Mesoporous silicas modified by dimethyldodecylamine exhibited the higher arsenate sorption capacities.

Sorption of basic dyes onto granulated pillared clays: thermodynamic and kinetic studies.

Effect of the granulation process onto the thermodynamic and kinetic sorption parameters of two basic dyes (Basic Yellow 28-BY 28 and Basic Green 4-BG 4) was evaluated in the present work. The charge surface properties of the surfactant-modified aluminium-pillared clay (CTAB-Al-Mont-PILC) particles were not modified, and the isoelectric point remains constant after high shear wet granulation. The Gibbs free energy of both BY 28 and BG 4 sorption was negative and decreased with the granulation; the endothermic nature of the sorption process was confirmed by the positive values of ΔH°. Adsorption kinetics of the two dyes, studied at pH 6 and 150 mg L(-1), follow the pseudo-first order kinetic model with observed rate constants of 2.5-4.2×10(-2) min(-1). The intraparticle diffusion model, proposed by Weber and Morris, was applied, and the intraparticle plots revealed three distinct sections representing external mass transfer, intraparticle diffusion and adsorption/desorption equilibrium. Diffusion coefficients, calculated from the Boyd kinetic equation, increased with the granulation and the particle size. Pseudo-first order kinetic constants, intraparticle diffusion rate constants and diffusion coefficients were determined for two other initial concentrations (50 and 100 mg L(-1)) and include in a statistical study to evaluate the impact of granulation and initial concentration on the kinetic parameters. Kruskal-Wallis tests, Spearman's rank order correlation and factor analysis revealed a correlation between (i) the diffusion coefficients and granulation, and between (ii) the intraparticle diffusion rate constants and initial concentration.

Aqueous heavy metals removal on amine-functionalized Si-MCM-41 and Si-MCM-48.

Ordered mesoporous silica with hexagonal and cubic structure, type MCM-41 and MCM-48 respectively, were synthesized under basic media using pure silica, cetyltrimethylammonium bromide and tetramethylammonium hydroxide, for MCM-41 and tetraethylorthosilica, cetyltrimethylammonium and NaOH for MCM-48. The expanded materials were prepared by post-synthesis method with N-N dimethyldodecylamine (DMDDA) and dodecylamine (DDA). Small angle X-ray diffraction, nitrogen adsorption-desorption measurements, FT-IR and thermogravimetry were used to characterize the samples. The expanded materials were tested for adsorption of Cd(2+), Co(2+), Cu(2+) and Pb(2+) in aqueous solution. Aminated materials were found to be fast adsorbents for metallic ions cation with affinity for Cu(2+), Pb(2+), than for Cd(2+) and Co(2+) from single solution. In mixed metallic ions cation solutions, competition by the adsorption sites is likely to occur, the adsorption preference is for Cu(2+)and Pb(2+). The kinetic of the reaction is very rapid and follow pseudo-second order and clearly indicated that Langmuir model describe better the for metal ions adsorption on aminated mesoporous material than Freundlich model.

Flavonoids: structural requirements for antiproliferative activity on breast cancer cells.

Several classes of flavonoids (flavones, flavanones, 2'-hydroxychalcones and flavan-4-ols) having a variety of substituents on A ring were investigated for their antiproliferative activity against MCF-7 human breast cancer cells. Structure-activity relationships of these compounds were discussed. 2'-hydroxychalcones and methoxylated flavanones were found to be potent inhibitors of MCF-7 cells growth whereas flavones and flavan-4-ols appeared to be weak inhibitory agents except 7,8-dihydroxyflavone.

Chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities.

Chalcones were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. In the present study, we have demonstrated for the first time that chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities: these enzymes being considered as important targets in the metabolic pathways of human mammary hormone-dependent cells. Our results showed that naringenin chalcone and 4-hydroxychalcone were the most effective aromatase and 17beta-hydroxysteroid dehydrogenase inhibitors with IC50 values of 2.6 and 16 microM respectively. In addition, inhibitory effects of some flavones and flavanones were compared to those of the corresponding chalcones. A structure-activity relationship was established and regions or/and substituents essential for these inhibitory activities were determined.

Estrogenic/antiestrogenic and scavenging properties of (E)- and (Z)-resveratrol.

Resveratrol, natural compound found in grapes and wine, has been reported to have a variety of health benefit properties. Based on the structural similarity to the synthetic estrogen diethylstilbestrol, we investigated estrogenic/antiestrogenic effects on human breast cancer cell lines, MCF-7 and MVLN, and scavenging properties using DPPH of both (E)- and (Z)-isomers. Both isomers increased the in vitro growth of MCF-7 cell lines at medium concentrations (10 and 25 microM) whereas the low concentrations (0.1 and 1 microM) had no effect and the high concentration (50 microM) decreased the cell growth and was cytotoxic. The 25 microM (E)-isomer alone was able to reduced the proliferation induced by the estradiol. Low concentrations of (E)- and (Z)-resveratrol (0.1 and 1 microM) and medium concentration 10 microM (Z)-resveratrol did not interfere with the estrogen receptor. In contrast, medium concentrations of (E)-resveratrol (10 and 25 microM) and (Z)-resveratrol (25 microM) functioned as superagonists of estradiol. Whatever the model used, MCF-7 or MVLN cell lines, (Z)-resveratrol was less effective than (E)-resveratrol. Extinction of DPPH and Fe(III) reduction experiments showed that both isomers of resveratrol could act as free radicals scavengers or pro-oxidant compounds. The properties of low concentrations of resveratrol raise the possibility that structure-function studies could lead to the development of more selective estrogen receptor agonists and antagonists, which could be useful as a therapeutic agent.

Radiation induced effects on cephalosporins: an ESR study.

PURPOSE: This paper reports experimental data on the ESR identification of four irradiated cephalosporins (cefpodoxime, cefsulodin, cefixime and ceftizoxime). MATERIALS AND METHODS: Equations to describe the ESR curves versus the dose and storage time were developed using mathematical procedures. RESULTS: Limits of detection (LOD) and limits of quantification (LOQ), estimated on the basis of the S/N ratios are 1.0+/-0.5 kGy and 2.5+/-0.5 kGy respectively. The yield of free radicals are in the range 4.6 10(19) - 2.2 10(20) radicals mol(-1) (G values from 0.1 to 0.4). Besides a very unstable situation (cefsulodin), the time limit of detection of free radicals after storage ranges from about 1 year to over 2 years. These time intervals are comparable with the shelf-life of the antibiotics and to the time limits found for 10 other cephalosporins described previously. Apart from qualitative detection, ESR spectrometry can be used for dose estimation. Exponential loss of ESR signal (first-order reaction) correlates well with the data. CONCLUSION: Given the sensitivity of ESR spectrometry, this experimental technique is promising for identification of irradiated cephalosporins.

Radiosterilization dosimetry of vitamins: an ESR study.

PURPOSE: As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as a sterilization process for medicinal products. Detection and dosimetry of pharmaceutical radiosterilization is a growing concern for numerous government regulatory agencies world-wide. MATERIALS AND METHODS: Equations to describe the ESR curves versus the dose and storage time were developed using mathematical procedures. For this investigation six vitamins (riboflavin, biotin, thiamine mononitrate, thiamine hydrochloride, folic acid and pyridoxine) were chosen as models. RESULTS: The yield of free radicals is in the range 1.7 10(18)-7.3 10(19) radicals mol(-1) (G values from 0.0003 to 0.025 mol J(-1)). Apart from qualitative detection, ESR spectrometry can be used for dose estimation; when an exponential function is applied to the variation of peak-to-peak amplitude on dose, the function correlates well with the data. Tests were carried out to investigate whether storage has an effect on the concentration of free radicals. In order to estimate the time limit of detection, decay curves were modelled using a bi-exponential function. From this, the time limit from the irradiation (25 kGy) for identification of irradiated vitamins by ESR was evaluated. In the commercial drug market, radicals should be detected for up to 2 years after irradiation; this probably will be the case for the vitamins studied, with the exception of folic acid and pyridoxine. CONCLUSION: The detection method based on ESR dosimetry seems promising. ESR dosimetry requires only small samples, and minimal time and effort for sample preparation; the measurement is non-destructive.

Radiation-induced effects on cefotaxime: ESR study.

As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as sterilization process for medicinal products. Detection and dosimetry of pharmaceuticals radiosterilization is a growing concern to numerous government regulatory agencies worldwide. In this context, it is necessary to find methods distinguishing between irradiated and nonirradiated pharmaceuticals. In the absence of suitable detection methods, our attention was focused on electron spin resonance (ESR) spectrometry. A third generation cephalosporin, cefotaxime, was chosen as model; this antibiotic is a potential candidate for radiation treatment due to its thermosensitivity. While the ESR spectra of a nonirradiated sample presents no signal, a signal, dependent of the irradiation dose, is found in irradiated samples. The number of free radicals was estimated by comparing the second integral from radiosterilized samples and a diphenyl-picrylhydrazyl reference. Estimation of the number of free radicals gives 1.9 x 10(20) radicals mol(-1) at 20 kGy. From this result, the G-value (number of radicals (100eV)(-1)) could be estimated to 0.3. Aside from qualitative detection, ESR spectrometry can be used for dose estimation. When quadratic, exponential or bi-exponential functions are applied to the variation of peak to peak amplitude vs. dose, these functions correlate well with the data. However, it is important to notice that linear function correlates well with the data for doses lower than 20 kGy. Since the radiation dose selected must be always based upon the bioburden of the products and the degree of sterility required (EN 552 and ISO 11137) 25kGy could no longer be accepted as a "routine dose" for sterilizing a pharmaceutical. Doses from 6kGy (ISO 11137) could be investigated and linear regression would appear to be the least expensive route to follow. The free radicals concentration appeared to not decrease during the 57 days of storage; the number generated during the irradiation allows the detection of radiosterilized cefotaxime up to two years after irradiation.

Inhibitory effect of curcuminoids on MCF-7 cell proliferation and structure-activity relationships.

Curcumin, demethoxycurcumin and bisdemethoxycurcumin are the yellow coloring phenolic compounds isolated from the spice turmeric. This study was part of a program correlating the biological activity and molecular structure of antitumor agents; the effect of these curcuminoids and cyclocurcumin (Cyclocur) was examined on the proliferation of MCF-7 human breast tumor cells. Curcuminoids appeared to be potent inhibitors, whereas Cyclocur was less inhibitory. To contribute to our understanding of the mechanism of antiproliferative activity of curcumin, cell cycle analysis was performed by propidium iodide staining and a flow cytometry technique. Curcumin exerts a cytostatic effect at G2/M which explains its antiproliferative activity. The presence of the diketone moiety in the curcumin molecule seems to be essential for the inhibitory activity.

ESR spectroscopy applied to the study of pharmaceuticals radiosterilization: cefoperazone.

As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as a sterilization process for medicinal products. Nevertheless, essentially for economic profits, an unauthorized and uncontrolled use of radiation process may be expected. In this context, it is necessary to find methods distinguishing between irradiated and unirradiated pharmaceuticals and, in the absence of suitable detection methods, our attention was focused on ESR spectrometry. In this paper, we examine the potential of ESR as an analytical tool in cefoperazone radiosterilization; this cephalosporin is a potential candidate for radiation treatment due to its thermosensitivity. While the ESR spectra of unirradiated sample present no intensity, a signal, dependent of the irradiation dose, is found exclusively in irradiated samples. The number of free radicals (2 x 10(17) radicals per g at 25 kGy) was estimated by comparison of the second integral from radiosterilized samples and DPPH. From this, the G-value could be estimated to 0.3. Limit of detection and limit of quantification are 0.5 kGy and 1 kGy, respectively. Aside from qualitative detection, ESR can be used for dose estimation. The dose-ESR response curves can be simulated by bi-exponential or power functions and the linear function can't be used for simulation even for low doses. Decay of radicals upon storage were simulated using bi-exponential function. The limit of detection of free radicals after irradiation at 25 kGy is 140 days.

Electron spin resonance detection of radiosterilization of pharmaceuticals: application to four nitrofurans.

The detection and dosimetry of radiosterilization of pharmaceuticals is a growing concern to numerous government regulatory agencies worldwide. In the absence of suitable detection methods, attention was focused on electron spin resonance (ESR) spectrometry. This paper reports experimental data on ESR dosimetry of irradiated nitrofurans (nitrofurantoin, nifuroxazide, nifurzide and nifurtoinol). Whereas the ESR spectrum of a non-irradiated sample shows no signal, a signal, that is dependent on the irradiation dose is observed with irradiated samples. The number of free radicals was calculated by comparing the second integral from radiosterilized samples and a Bruker strong pitch reference; the values were in the range 1.1 x 10(18)-1.5 x 10(19) radicals mol-1 (G = 0.003-0.03). In addition to qualitative detection, ESR spectrometry can be used for dose determination. When a bi-exponential function is applied to the variation of the peak-to-peak amplitude versus dose, the function correlates well with the data. However, an exponential function, easier to use than a bi-exponential function, will probably be sufficient for dose determination by retrospective dosimetry. Decay of radicals upon storage was modelled using a bi-exponential function. From this, the time limit from the irradiation (25 kGy) for identification of irradiated nitrofurans by ESR can be evaluated. With regard to the commercial aspects of drugs, radicals should be detected up to 2 years after irradiation. The kinetic decrease makes discrimination between irradiated and non-irradiated nitrofurans possible even after storage for up to 2 years, except for nifurtoinol.

ESR dosimetry of irradiated ascorbic acid.

PURPOSE: As an alternative to heat and gas exposure sterilization, ionizing radiation is gaining interest as a sterilization process for medicinal products. The aim of this work was to develop equations to describe the ESR curves versus dose and storage time after gamma irradiation of ascorbic acid. Several ESR data sets previously acquired in this laboratory were adopted to check the performance of the models. RESULTS: Limit of detection and limit of discrimination are respectively 0.5 kGy and 2 kGy for ascorbic acid. Linear regression is applicable for doses lower than 25 kGy. Since the radiation dose selected must always be based upon the bioburden of the products and the Degree of Sterility required (ANSI/AAMI/ISO 11137), doses in the range 5-25 kGy could be investigated and linear regression would appear to be the least expensive route to follow and gives good results. Quadratic fit, power function, exponential function and bi-exponential functions are of more general applicability to predict irradiation dose. Decay kinetics for radicals versus storage were considered. Nonhomogeneous kinetics with time-dependent rate (diffusion-controlled second-order reaction) and bi-exponential function appeared valid to reproduce the experimental data. Discrimination between irradiated and unirradiated ascorbic acid is possible after a storage of 800 days. CONCLUSIONS: It is worth noting that, at present, ESR is the only technique which proves to be suitable for identification and quantification purposes in irradiated pharmaceuticals. Moreover, other features such as sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques.

Radiation effects on dopamine and norepinephrine.

PURPOSE: Radiation sterilization is becoming increasingly popular for the sterilization of many pharmaceutical products. We have investigated the gamma radiation induced effects on dopamine and norepinephrine by ESR spectroscopy. RESULTS AND DISCUSSION: Equations to describe the evolution of the ESR curves versus doses and time of storage are presented. Linear regression is, for dopamine hydrochloride, applicable for doses ranging from 10 to 25 kGy. Since the radiation dose selected must always be based upon the bioburden of the products and the degree of sterility required, doses in the range 10-25 kGy could be investigated and linear regression would appear to be the least expensive route to follow and gives good results. The comportment of noradrenaline bitartrate is more complex and the use of linear regression would appear more hazardous especially for low doses. For doses higher than 25 kGy, a more general equation is required. Power function using only 2 parameters could give good results but must be validated. Decay kinetics for radicals versus storage were considered. Non-homogeneous kinetics with time dependent rate constant and bi-exponential function appeared valid to reproduce the decay of radicals for, respectively, dopamine and norepinephrine. CONCLUSIONS: It is worth noting that, at present, ESR is the only technique which proved to be suitable for identification and quantification purposes in irradiated pharmaceuticals. Moreover, other features such as sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques.

Radiation sterilization of formoterol.

PURPOSE: Radiation sterilization is becoming increasingly popular for the sterilization of many pharmaceutical products. We have investigated the gamma radiation induced effects on formoterol fumarate by HPLC and ESR spectroscopy. RESULTS AND DISCUSSION: Numerical simulation of the evolution of the ESR signal versus dose was performed using linear regression, quadratic fit and power function. The shape of the dosimetric curve is linear in the range 5-30 kGy. Owing to the weak number of free radicals generated during the irradiation, the accuracy of measurements is low. For a dose of 25 kGy, discriminating irradiated from unirradiated samples is possible if the storage period is less than 250 days. The comparison between chromatographic profiles of irradiated and unirradiated samples showed minor differences. CONCLUSIONS: From our preliminary results, radiosterilization of formoterol fumarate may be technically feasible. Estimation of the irradiation dose by ESR may be possible but, due to the weak number of free radicals generated during the irradiation, the accuracy of measurements appeared low.

The effect of gamma radiation on the degradation of salbutamol.

The use of ionizing radiation for sterilization of pharmaceuticals is now a well established technology. Degradation of salbutamol was investigated after gamma irradiation using HPLC and ESR spectroscopy. HPLC evidenced the formation of radiolytic products after gamma irradiation. Salbutamol showed a degradation of nearly 2% at 25 kGy. Sterilization of salbutamol in the liquid state appeared not technically feasible. Simulation of the increase of free radicals versus dose was performed using linear and polynomial regression. These radicals could be detected even after a storage period of more than 12 months.