Plasma kinetics of lutein, zeaxanthin, and 3-dehydro-lutein after multiple oral doses of a lutein supplement

BACKGROUND: Adequate intake of lutein is postulated to reduce the risk of age-related macular degeneration, but kinetic information for developing a dosing regimen is sparse. OBJECTIVE: The objective was to characterize lutein plasma kinetics in a multiple dosing design and to assess the effects of lutein intake on concentrations of other plasma carotenoids. DESIGN: After a run-in period of 7 d, 19 healthy volunteers were assigned to receive daily oral doses of 4.1 mg lutein (n = 8; group 1) or 20.5 mg lutein (n = 8; group 2) for 42 d or no lutein (n = 3; control group). The supplement contained 8.3% zeaxanthin relative to lutein (100%). The time profiles of plasma xanthophyll concentrations were monitored over the dosing phase, and samples were collected frequently on day 42 and for 24 d after dosing. RESULTS: Average plasma all-E-lutein concentrations increased from 0.14 to 0.52 +/- 0.13 and 1.45 +/- 0.69 micromol/L in groups 1 and 2, respectively. Dose-normalized lutein bioavailability in group 2 was approximately 60% of that in group 1. Kinetic disposition half-life did not differ significantly between groups. On average, dosing for 18 d was required to reach a >90% fraction of the steady state concentration, which is consistent with an effective half-life for accumulation of approximately 5.6 d. Plasma kinetics of all-E-lutein were paralleled by those of all-E-3-dehydro-lutein. Kinetic analysis indicated formation of all-E-3-dehydro-lutein from lutein. Lutein was well tolerated and did not affect the concentrations of other carotenoids. CONCLUSION: Long-term supplementation with 4.1 and 20.5 mg lutein as beadlets increased plasma lutein concentrations approximately 3.5- and 10-fold, respectively.     

A new PCR-ELISA for diagnosis of visceral leishmaniasis in blood of HIV-negative subjects

The PCR-ELISA represents a promising advance for diagnosis of visceral leishmaniasis (VL) in blood samples. However, the method has been validated mostly with HIV-positive patients who are known to have high levels of parasitaemia. We developed a new PCR-ELISA assay for specific detection of Leishmania in patients' blood and validated it in Nepalese subjects with clinically suspected VL, almost all of whom were HIV-negative. For blood samples, PCR-ELISA was more sensitive (83.9%) than conventional PCR (73.2%), and demonstrated 100% and 87.2% specificity when using healthy controls who had never travelled to a VL-endemic area and controls from a VL-endemic area as references, respectively. We have demonstrated the ability of PCR-ELISA to detect parasites in blood of HIV-negative patients. The method could be used for epidemiological as well as clinical purposes, as it reduces the need for traumatic bone marrow sampling and risky spleen aspiration.     

The anaphase-promoting complex: a key factor in the regulation of cell cycle

Events controlling cell division are governed by the degradation of different regulatory proteins by the ubiquitin-dependent pathway. In this pathway, the attachment of a polyubiquitin chain to a substrate by an ubiquitin-ligase targets this substrate for degradation by the 26S proteasome. Two different ubiquitin ligases play an important role in the cell cycle: the SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC). In this review, we describe the present knowledge about the APC. We pay particular attention to the latest results concerning APC structure, APC regulation and substrate recognition, and we discuss the implication of these findings in the understanding the APC function.     

Major depression as a risk factor for early institutionalization of dementia patients living in the community

OBJECTIVE: Although depression is known to be frequently associated with dementia, it is nonetheless under-diagnosed and under-treated among this patient population. Its effect on outcome for dementia patients is thought to be substantial, because depression appears to induce higher than normal rates of disability as well as supplementary cognitive decline. The aim of this study was to measure the impact of major depression on the institutionalization rate of community-dwelling dementia patients. DESIGN: Prospective cohort study. SETTING: Paris, France. PARTICIPANTS: Three-hundred forty-eight consecutive dementia outpatients of a geriatric clinic (mean age: 81 years, 69.8% women, 65.5% dementia of Alzheimer's type, mean baseline MMSE score: 20.5), followed between 1997 and 2002 (mean follow-up: 20.5 months). RESULTS: Twenty-five percent of the patients met the criteria of major depression at baseline, and only 30.3% of these received antidepressant medication. Major depression at baseline was independently associated with nursing home admission within one year of the baseline assessment. Antidepressant medication tended to protect against this outcome, but not to a statistically significant extent. CONCLUSIONS: Major depression at baseline is an independent risk factor for early institutionalization of dementia sufferers. Early institutionalization is defined in this study as nursing home placement within a year of diagnosis with dementia at our specialized outpatient center. The study highlights the need for better management of depression among dementia outpatients. Further investigation is needed to evaluate the protective effect of antidepressant medication (and/or non-pharmacological therapies) on the institutionalization rate.     

Structural mechanisms of costimulation

Recent studies have highlighted the structural requirements for T cell costimulation and have revealed unusual modes of dimerization for the cytolytic T lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7 ligands. These distinctive quaternary structures potentially endow both receptor and ligand with bivalent binding properties, which suggests a number of mechanistic features relevant to signaling. These include the potential to form a highly ordered, alternating network of CTLA-4 and B7 homodimers that may represent the organization of these molecules and their associated signaling partners within the immunological synapse. Primary sequence and structural considerations suggest that some aspects of the organizational and mechanistic features associated with the CTLA-4-B7 complexes may extend to other members of the costimulatory receptor-ligand family. An examination of the signaling mechanisms within the costimulatory receptor-ligand family provides an excellent framework to consider the general principles that are relevant to cell surface receptor-mediated signaling events.     

CT and F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers

Purpose: To validate a computed tomography (CT) and ¹⁸F-deoxyglucose (FDG) image fusion procedure and to evaluate its usefulness to facilitate target definition and treatment planning in three-dimensional conformal radiation therapy (3D-CRT) for non–small-cell lung cancer.

Methods and Materials: Twelve patients were assessed by CT and FDG-coincidence mode dual-head gamma camera (CDET) before radiotherapy. The patients were placed in a similar position during CT and FDG-CDET. Matching was achieved by minimizing the cost function by 3D translation and rotation between four landmarks drawn on the patient’s skin. Virtual simulation was performed from image fusion and estimated dose–volume histograms (DVH) were calculated.

Results: Quantitative analysis indicated that the matching error was < 5 mm. Fusion of anatomic and metabolic data corrected staging of lymph nodes (N) for 4 patients and staging of metastases for 1 patient. In these 5 patients, DVH revealed that the lung volume irradiated at 20 Gy (Vl₂₀) was decreased by an average of 22.8%, and tumor volume irradiated at the 95% isodose (V₉₅) was increased by 22% and 8% for 2 patients, respectively, and was decreased by an average of 59% for 3 patients after fusion. No difference in terms of Vl₂₀ and V₉₅ was observed for the other 7 patients.

Conclusion: We have validated CT and FDG-CDET lung image fusion to facilitate determination of lung cancer volumes, which improved the accuracy of 3D-CRT.     

The choroid plexus--cerebrospinal fluid system: undervaluated pathway of neuroendocrine signaling into the brain

The cerebrospinal fluid (CSF) is a major part of the extracellular fluid of the central nervous system. The function of the CSF and the tissue that secretes it, the choroid plexus (CP) has traditionally been thought as providing the brain with essential nutrients, removing products of neuronal activity of the central nervous system, and providing mechanical support for the brain's fragile cellular network. More recent studies suggest, however, that the CP and CSF system play a much more active role in the function of the central nervous system being a target, source and pathway for neuroendocrine signaling within the brain.