The SAMBA quick-EXAFS monochromator: XAS with edge jumping.

Results and performances of the QEXAFS double monochromator of the SAMBA beamline (Synchrotron SOLEIL) are presented. The device is capable of speeds of up to 40 Hz, while giving the user the possibility to choose the amplitude of the scan from 0.1° to 4° in a few seconds. The device is composed of two independent units and it is possible to perform scans alternating between two different crystals, literally jumping from low (4 keV) to high (37 keV) energies.

Advanced design of a x-ray absorption spectroscopy setup for measuring transition metals speciation in molten carbonates, hydroxides and hydrogenosulfates.

Battery recycling is currently becoming a crucial issue. One possible treatment path involves the use of molten salts. A mechanistic understanding of the underlying processes requires being able to analyze in situ speciation in molten salts at various temperatures. This can be advantageously achieved using x-ray absorption spectroscopy, the use of Quick-EXAFS facilities being particularly appropriate. Consequently, this paper presents the design and development of a new setup allowing carrying out Quick-EXAFS experiments in oxidizing molten salts at high temperatures. We describe the different components of a cell and the performance of the heating device. We illustrate the capabilities of the setup by analyzing the temperature evolution of Co speciation upon dissolution of LiCoO2, a typical battery electrode material, in molten carbonates, hydroxides, and hydrogenosulphates.

Axial acoustic field along a solid-liquid fluidized bed under power ultrasound.

This work investigates the ultrasound propagation within a liquid-solid fluidized bed. The acoustic mapping of the reactor is achieved by means of a hydrophone. A spectral analysis is carried out on the measured signals to quantify the cavitation activity. The effects of several parameters on the spectral power distribution is appraised - including emitted ultrasound power, liquid superficial velocity and solid hold-up. Results show that increasing US power promotes a higher energy transfer from the driving frequency toward the broad-band noise - which is the signature of transient cavitation - and yields a stronger acoustic shielding. The presence of a flow opposite to the acoustic streaming may affect the sonoreactor behavior by sweeping the cavitation bubbles away from the ultrasonic horn. Finally the presence of millimeter sized particles significantly increases wave attenuation, presumably due to viscous losses on the one hand, and through the contribution of their surface defects to bubble nucleation on the other hand. Moreover, the influence of the solid hold-up appears to depend upon the particle material (glass or polyamide).

Pharmacokinetics of Ferrous Sulphate (Tardyferon®) after Single Oral Dose Administration in Women with Iron Deficiency Anaemia.

Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration.

Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.

Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16(INK4a) derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation.

Primary cutaneous large B-cell lymphoma: the relation between morphology, clinical presentation, immunohistochemical markers, and survival.

The histogenesis, morphology, immunophenotype, and clinical behavior of cutaneous large B-cell lymphomas (CLBCL) are largely a matter of controversy. We performed an investigation to determine whether CLBCL have features that differentiate them from other large B-cell lymphomas and whether CLBCL is itself a heterogeneous group. To this end, we reviewed the main characteristics of a series of 32 cases of LBCL found in the skin. We reviewed the clinical findings and paraffin sections of the tumors from these 32 patients. The immunohistochemical study performed included p53, MIB1, Bcl2, Bcl6, and CD10 markers. We carried out statistical analysis of these data (univariate and multivariate), seeking an association between the features of the tumors and clinical outcome, as defined by failure-free survival time. Only one patient died as a consequence of the lymphoma. Nevertheless, the accumulated probability of survival without failure at 48 months was 0.46. The number, type, and localization of the lesions were not associated with variations in either survival or failure-free survival. The expression of p53 was negative in this group of CLBCL, whereas Bcl-2 expression or localization in the lower leg did not relate to any other significant feature. Histologic examination of the cases disclosed three different groups: Grade III follicular lymphomas (FLs), monomorphous large B-cell lymphomas (LBCL type I), and LBCL with an admixed component of small B-lymphocytes (LBCL type II). Grade III FL (11 cases) tended to be found in the head and neck and showed CD10 expression in a majority of cases. A higher probability of lymph node relapses was associated with cases located in the head and neck and with CD10+ tumors. Cutaneous large B-cell lymphomas are indolent tumors, but follow an insidious course. Our data support the interpretation that CLBCL is a heterogeneous condition; comprises some LBCL derived from CD10+ germinal center cells which manifests more frequently as tumors in the head and neck region, with an increased probability of relapse in lymph nodes [1] and has some distinctive morphologic features. The existence of a component of small B-cells within the other CLBCL could lend support to the theory that some of these tumors, more than arise de novo, may have originated in preexistent small B-cell lymphomas, but no firm evidence of this is provided in this study.

Gastrointestinal absorption of drugs: methods and studies.

Physico-chemical descriptors of drug molecules are often not adequate in predicting their oral bioavailability. In vitro methods can be useful in evaluating some of the different factors contributing to bioavailability. While physical parameters such as drug solubility may effect oral bioavailability, in most cases, the major determining factors are likely to be metabolism, and absorption at the intestinal level. Metabolism may be preabsorptive, as with peptides, or during absorption, particularly as a result of the activity of the intracellular enzyme CYP3A4. Absorption may be transcellular (membrane diffusion, carrier-mediated, endocytosis) or paracellular, while p-glycoprotein activity in the apical cell membrane may limit bioavailability by expelling drugs from the mucosal cells. Knowledge of the absorption mechanism is important in determining formulation strategies. The different in vitro techniques used to study absorption have advantages and disadvantages. Ussing chambers can be useful to measure bidirectional transport, but most studies use simple salt media, and full tissue viability is doubtful. Caco-2 cell monolayers are human cells, but the system is static, and gives very low rates of transport, and exagerated enhancement of the paracellular route compared with small intestine. The rat everted gut sac incubated in tissue culture medium maintains tissue viability and gives reliable data, although it is a closed system. In situ perfusion gives no information on events at the cellular level, and absorption may be reduced by anaesthesia and surgical manipulation. In vivo perfusion in man, with multichannel tubes, gives valuable data, but is not practical for screening. Pharmacokinetic modelling can also give useful data such as the existence of different absorption sites. Permeability values from the literature show that for small hydrophilic molecules, which pass by the paracellular route, the improved everted sac gives values close to those for humans, while values with Caco-2 cells are orders of magnitude lower.

The roles of P-glycoprotein and intracellular metabolism in the intestinal absorption of methadone: in vitro studies using the rat everted intestinal sac.

Methadone is used as a treatment for opiate detoxification in methadone maintenance programs. Intra- and inter-patient variations in methadone bioavailability have been observed after oral methadone treatment and this makes it difficult to predict a dosing regimen. Intestinal absorption and metabolism could explain these variations. The in vitro gut sac model was used to study the intestinal absorption of methadone, and it confirmed that methadone is a substrate for P-glycoprotein. The transport of methadone was increased in presence of P-gp inhibitors verapamil and quinidine. The appearance of a major metabolite of methadone, 2-ethylidene-1, 5-dimethyl-3, 3-diphenyl pyrrolidine (EDDP) in the gut sac contents also demonstrated the existence of intestinal metabolism of methadone.

An improved everted gut sac as a simple and accurate technique to measure paracellular transport across the small intestine.

An improved everted gut sac system has been developed in which the sacs were carefully prepared from rat small intestine and incubated in tissue culture medium. Under these conditions, the tissue showed good morphology at the electron microscope level, and was metabolically active for up to 2 h at 37 degrees C. Mannitol, an established probe of paracellular transport, was transported from the mucosal to the serosal side of the sac tissue. Excellent kinetic data showed that transport was linear up to 75 min and over a wide range of concentrations (0.025 - (10 mM). Mannitol was not detected in the tissue and transport was enhanced by EGTA, confirming the paracellular route of passage. Sacs prepared from colon also showed mannitol transport, but at a slower rate. Comparisons with Caco-2 cell monolayers showed that the everted sacs exhibited higher levels of paracellular transport than the cultured cell line. The improved everted gut sac system is an inexpensive and relatively simple technique with considerable potential as an in vitro tool to study the mechanisms, kinetics and enhancement of drug absorption across the small intestine at different sites and in the colon.

[What is the method of choice for hemodynamic monitoring in liver transplantation?]. / Quel monitorage hémodynamique lors des transplantations hépatiques?

Orthotopic liver transplantation requires close hemodynamic monitoring. Technological advances provide new possibilities of improving this monitoring. The most recent devices are the mixed venous oxygen saturation catheter, which gives continuous SVO2 values, and the right ejection fraction catheter used discontinuously. Our experience of 100 liver transplantations has enabled us to investigate the advantages of these catheters over the conventional Swan Ganz catheters.

Primary systemic amyloidosis. A report of 2 cases.

We report 2 cases of primary systemic amyloidosis. A monoclonal gammopathy was confirmed at the postmortem examination of the first patient. An extensive search for evidence of chronic infection, inflammation, neoplasms and paraproteinemia was conclusively negative in the other patient. The recognition of cutaneous signs of primary systemic amyloidosis is crucial to insure a rapid management aimed at postponing the fatal issue of the disease.