Optical studies on contractile structures in frog muscles. analysis of components at rest and of responses related to contractile events.

A new device is described which allows the study of optical properties of a small area (< 2500 μm²) of a single fiber of skeletal muscle or of thin myocardial trabeculae, under controlled electrophysiological conditions (voltage or current clamp). The intensity of scattering by myocardial trabeculae is less prominent than that of skeletal fibers. In both tissues, the absorbance after correction, corresponds to the components of the preparations. Studies with polarized u.v. light indicated the presence of oriented compounds with positive dichroism ratios around 280 nm and negative ratio around 260 nm. In both tissues, scattering and absorbance increase during a contraction. An absorbance change in the visible part of the spectrum is recorded during a single twitch and suggests early biochemical changes in the contracting fibers. An absorbance increase around 285 nm preceeds the initiation of mechanical events recorded with a mechanotranducer and changes in the dichroic ratios would correspond to an increase in the fraction of oriented aromatic aminoacids and to a decrease in bound nucleotides. Control measurements indicated that the optical phenomena were intrinsic properties of the preparations.     

Cell interactions between human progenitor-derived endothelial cells and human mesenchymal stem cells in a three-dimensional macroporous polysaccharide-based scaffold promote osteogenesis

Several studies have reported the benefits of mesenchymal stem cells (MSCs) for bone tissue engineering. However, vascularization remains one of the main obstacles that must be overcome to reconstruct large bone defects. In vitro prevascularization of the three-dimensional (3-D) constructs using co-cultures of human progenitor-derived endothelial cells (PDECs) with human bone marrow mesenchymal stem cells (HBMSCs) appeared as a potential strategy. However, the crosstalk between the two lineages has been studied in two-dimensional (2-D), but remains unknown in 3-D. The aim of this study is to investigate the cell interactions between PDECs and HBMSCs in a porous matrix composed of polysaccharides. This biodegradable scaffold promotes cell interactions by inducing multicellular aggregates composed of HBMSCs surrounded by PDECs. Cell aggregation contributes to the formation of junctional proteins composed of Connexin43 (Cx43) and VE-cadherin, and an activation of osteoblastic differentiation of HBMSCs stimulated by the presence of PDECs. Inhibition of Cx43 by mimetic peptide 43GAP27 induced a decrease in mRNA levels of Cx43 and all the bone-specific markers. Finally, subcutaneous implantations for 3 and 8 weeks in NOG mice revealed an increase in osteoid formation with the tissue-engineered constructs seeded with HBMSCs/PDECs compared with those loaded with HBMSCs alone. Taking together, these results demonstrate that this 3-D microenvironment favored cell communication, osteogenesis and bone formation.     

Dual-release formulation, a novel principle in L-dopa treatment of Parkinson's disease

A single morning dose of dual-release formulation was compared with a slow-release formulation of L-dopa plus benserazide in a randomized, double-blind, cross-over study in 16 fluctuating patients with PD. The mean time to "on" was shorter with the dual-release formulation (43 +/- 31 minutes) than with the slow-release formulation (81 +/- 39 minutes) (p < 0.001), whereas the mean time to relapse to "off" was similar for both formulations. The dual-release formulation had a significantly shorter time to reach peak concentration (t(max)) and greater maximum concentration (C(max)) and area under the plasma concentration time curve (AUC(0--5 h)) than the slow-release formulation, whereas apparent elimination half-life (t(1/2)) was similar for both formulations.     

In vitro cytocompatibility of radio-opacifiers used in ureteral endoprosthesis

Ureteral endoprostheses are urinary catheters made of polymeric biomaterials made radio-opaque through the addition of X-ray absorbing additives such as barium, bismuth, tantale or tungsten. The aim of this work was to study the in vitro toxicity of solutions of these radio-opacifiers using two cell culture models. Primary-cultures of human urothelial cells (HUC) arising from normal adult urinary tract and permanent urothelial cell line were used. Solutions at different dilutions were placed into the wells containing monolayers of confluent cells. After 24 h incubation period, the solutions were removed and cell viability and cell metabolic activity tests were performed (Neutral Red assay and MTT assay). At a concentration lower than 1 mg l(-1) the different radio-opacifiers used showed no toxicity. From 1 to 3 mg l(-1) one can note a significant dose-dependent decrease of cell metabolic activity of solely HUC for barium chloride. At 3 mg l(-1) one can note a significant deleterious effect on HUC metabolic activity, with bismuth and tantale. For tungsten, there is no deleterious effect, but on the contrary a significant increase in HUC metabolic activity at a 0.5 mg l(-1) concentration. None of the solutions did provoke alterations in HUC viability for concentrations less than 3 mg l(-1). Interestingly, for permanent cell line one can note a solely significant decrease of cell viability at 3 mg l(-1) for tantale. All the other tested salts on permanent cell line were not significantly different from controls for cell viability as well as cell metabolic activity. HUC culture model may be of relevance for the screening of radio-opacifiers intended for ureteral endoprostheses.     

Influence of simulated weightlessness on the oral pharmacokinetics of acetaminophen as a gastric emptying probe in man: a plasma and a saliva study

This study evaluated the effect of simulated weightlessness on gastric emptying, using acetaminophen as a probe and -6 degrees head-down bed rest to simulate zero gravity. Eighteen volunteers were given 1 g of acetaminophen orally before the bed rest and at days 1, 18, and 80. Cmax, tmax, AUC0- infinity, AUC0-t, and t1/2 were calculated for plasma and saliva. The plasma Cmax showed a significant increase (10.43 microg/mL [day 1] to 14.74 microg/mL [day 80]), while tmax significantly decreased (1.41 h [day 1] to 0.91 h [day 80]). Similar results were obtained with saliva, and there were significant increases in the AUCs. The good correlation between the plasma and saliva data suggests that saliva sampling can be valid for acetaminophen pharmacokinetics. The changes in Cmax and tmax indicated more rapid drug absorption, which could have been as a result of faster gastric emptying or an increased blood flow to the intestine.     

Development and validation of a patient-based health-related quality of life questionnaire in schizophrenia: the S-QoL

We developed a self-administered instrument to assess health-related quality of life (HRQL) among people with schizophrenia. The S-QoL, based on Calman's approach to the subject's point of view, is a multidimensional instrument that is sensitive to change. The scale is a 41-item questionnaire with eight subscales (psychological well-being, self-esteem, family relationships, relationships with friends, resilience, physical well-being, autonomy and sentimental life) and a total score. In-depth interviews with patients determined the pertinent issues for item development. The validation study, performed with 207 patients, showed high internal consistency reliability, reproducibility and responsiveness. Construct validity was confirmed using established clinical and HRQL measures. S-QoL covers domains that differ from areas tapped in other measures, with greater responsiveness. The S-QoL is an efficient instrument for the measurement of the impact of schizophrenia on individuals' lives.