Generation of induced pluripotent stem cell lines IRMBi003-A and IRMBi003-B from a healthy donor to model Alzheimer's disease.

Induced Pluripotent Stem Cell (iPSC) lines derived from healthy individuals are helpful and essential tools for disease modelling. Here, we described the reprogramming of skin fibroblasts obtained from a healthy 59-year-old individual without Alzheimer's disease. The generated iPSC lines have a normal karyotype, expressed pluripotency markers, and demonstrated the ability to differentiate into the three germ layers. The iPSC lines will be used as controls to study Alzheimer's disease mechanisms.

Establishment of induced pluripotent stem cells IRMBi005-A from a patient with sporadic Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurological disorder and the most common form of dementia worldwide. Sporadic Alzheimer's disease (sAD) cases are the main forms, over 95% of AD cases, but still poorly understood. Thereby there is a crucial need to develop in vitro models for studying this multifactorial disorder. Here, we report the reprogramming of skin fibroblasts from a 57-years-old male donor. The new generated iPSC cell line has a normal karyotype and, is pluripotent since it demonstrates the ability to differentiate in vitro into the three germ layers. This iPSC line will be used to understand pathological mechanisms of sAD.

Single-step production of autologous bovine platelet concentrate for clinical applications in cattle.

Platelet concentrate (PC) is an alternative therapy to treat mastitis in dairy cattle and is an alternative treatment for reproduction problems such as endometritis. Unfortunately, double-centrifugation processing methods described are time-consuming, require specialized laboratory equipment, and are usually done in a heterologous way, which risks herd health. To overcome this limitation, we evaluated single-step bovine PC processing methods readily applicable to a farm setting using an autologous conditioned plasma (ACP) production system. We investigated the hematologic findings, cytokines, and growth factors of the obtained PC samples. Autologous conditioned plasma was prepared using whole blood (WB) from 4 cows (group 1) using single-step centrifugation and 16 different processing methods. The 2 protocols that yielded the highest ratio of platelet to white blood cell (WBC) concentration were ACP-1 [720 × g (2,200 rpm), 5 min] and ACP-2 [929 × g (2,500 rpm), 3 min]. They were subsequently reproduced and compared using WB from 8 cows (group 2). Hematologic findings were quantified, IL-1ß (cytokine) and growth factors [platelet-derived growth factor (PDGF), transforming growth factor (TGF)-ß, bovine fibroblast growth factor (b-FGF)] were measured, and enrichment factors were compared between samples and processing methods. Hematological characteristics and platelet enrichment varied markedly among tested protocols and all were statistically different from WB. Protocol ACP-2 resulted in significantly greater platelet enrichment (mean 169% of WB) than ACP-1 (125% of WB). We found no significant difference between the 2 ACP preparation protocols with regard to leukocyte reduction (7.53-9.75% WBC compared with WB) or growth factor enrichment (124-125% PDGF, 95-100% TGF-ß, 102-104% b-FGF, and 56-74% IL-1ß compared with WB). In conclusion, both ACP protocols yielded a platelet concentration shown to promote healing for clinical applications in cattle, and the ACP-2 protocol resulted in a greater degree of platelet enrichment. Therefore, this protocol could be used for ACP production for clinical applications in cattle.

FLAIR Vascular Hyperintensities as a Surrogate of Collaterals in Acute Stroke: DWI Matters.

BACKGROUND AND PURPOSE: FLAIR vascular hyperintensities are thought to represent leptomeningeal collaterals in acute ischemic stroke. However, whether all-FLAIR vascular hyperintensities or FLAIR vascular hyperintensities-DWI mismatch, ie, FLAIR vascular hyperintensities beyond the DWI lesion, best reflects collaterals remains debated. We aimed to compare the value of FLAIR vascular hyperintensities-DWI mismatch versus all-FLAIR vascular hyperintensities for collateral assessment using PWI-derived collateral flow maps as a reference. MATERIALS AND METHODS: We retrospectively reviewed the registries of 6 large stroke centers and included all patients with acute stroke with anterior circulation large-vessel occlusion who underwent MR imaging with PWI before thrombectomy. Collateral status was graded from 1 to 4 on PWI-derived collateral flow maps and dichotomized into good (grades 3-4) and poor (grades 1-2). The extent of all-FLAIR vascular hyperintensities and FLAIR vascular hyperintensities-DWI mismatch was assessed on the 7 cortical ASPECTS regions, ranging from 0 (absence) to 7 (extensive), and associations with good collaterals were compared using receiver operating characteristic curves. RESULTS: Of the 209 included patients, 133 (64%) and 76 (36%) had good and poor collaterals, respectively. All-FLAIR vascular hyperintensity extent was similar between collateral groups (P = .76). Conversely, FLAIR vascular hyperintensities-DWI mismatch extent was significantly higher in patients with good compared with poor collaterals (P < .001). The area under the curve was 0.80 (95% CI, 0.74-0.87) for FLAIR vascular hyperintensities-DWI mismatch and 0.52 (95% CI, 0.44-0.60) for all-FLAIR vascular hyperintensities (P < .001 for the comparison), to predict good collaterals. Variables independently associated with good collaterals were smaller DWI lesion volume (P < .001) and larger FLAIR vascular hyperintensities-DWI mismatch (P = .02). CONCLUSIONS: In acute ischemic stroke with large-vessel occlusion, the extent of FLAIR vascular hyperintensities does not reliably reflect collateral status unless one accounts for DWI.

Walking with eyes closed is easier than walking with eyes open without visual cues: The Romberg task versus the goggle task.

BACKGROUND: The Romberg test, with the subject standing and with eyes closed, gives diagnostic arguments for a proprioceptive disorder. Closing the eyes is also used in balance rehabilitation as a main way to stimulate neural plasticity with proprioceptive, vestibular and even cerebellar disorders. Nevertheless, standing and walking with eyes closed or with eyes open in the dark are certainly 2 different tasks. We aimed to compare walking with eyes open, closed and wearing black or white goggles in healthy subjects. METHODS: A total of 50 healthy participants were randomly divided into 2 protocols and asked to walk on a 5-m pressure-sensitive mat, under 3 conditions: (1) eyes open (EO), eyes closed (EC) and eyes open with black goggles (BG) and (2) EO, EO with BG and with white goggles (WG). Gait was described by velocity (m·s(-1)), double support (% gait cycle), gait variability index (GVI/100) and exit from the mat (%). Analysis involved repeated measures Anova, Holm-Sidak's multiple comparisons test for parametric parameters (GVI) and Dunn's multiple comparisons test for non-parametric parameters. RESULTS: As compared with walking with EC, walking with BG produced lower median velocity, by 6% (EO 1.26; BG 1.01 vs EC 1.07 m·s(-1), P=0.0328), and lower mean GVI, by 8% (EO 91.8; BG 66.8 vs EC 72.24, P=0.009). Parameters did not differ between walking under the BG and WG conditions. CONCLUSION: The goggle task increases the difficulty in walking with visual deprivation compared to the Romberg task, so the goggle task can be proposed to gradually increase the difficulty in walking with visual deprivation (from eyes closed to eyes open in black goggles).

(68)Ga-AMBA and (18)F-FDG for preclinical PET imaging of breast cancer: effect of tamoxifen treatment on tracer uptake by tumor.

INTRODUCTION: AMBA is a bombesin analogue that binds to GRPr. In a mouse model of estrogen-dependent human breast cancer, we tested whether (68)Ga-AMBA can be used for PET detection of GRPr-expressing tumors and could be more accurate than (18)F-FDG to monitor tumor response to hormone therapy. METHODS: The radiolabeling of (68)Ga-AMBA was automated using a R&D Synchrom module. ZR75-1, a breast cancer cell line, was xenografted in nude mice. (68)Ga-AMBA tumor uptake was compared with that of (18)F-FDG before and after treatment with tamoxifen. RESULTS: AMBA was (68)Ga-radiolabelled in 30min with 95.3% yield and purity≥98%. Prior to treatment, (68)Ga-AMBA was highly concentrated into tumors (tumor to non-tumor ratio=2.4 vs. 1.3 with (18)F-FDG). With tamoxifen treatment (n=6) (68)Ga-AMBA uptake plateaued after 1week and decreased after 2weeks, with a significant reduction compared to controls (n=4). In contrast the effect of tamoxifen treatment could not be appreciated using (18)F-FDG. CONCLUSIONS: (68)Ga-AMBA appeared better than (18)F-FDG to visualize and monitor the response to hormone treatment in this breast cancer model.

Sea level rise during past 40 years determined from satellite and in situ observations.

The 3.2 +/- 0.2 millimeter per year global mean sea level rise observed by the Topex/Poseidon satellite over 1993-98 is fully explained by thermal expansion of the oceans. For the period 1955-96, sea level rise derived from tide gauge data agrees well with thermal expansion computed at the same locations. However, we find that subsampling the thermosteric sea level at usual tide gauge positions leads to a thermosteric sea level rise twice as large as the "true" global mean. As a possible consequence, the 20th century sea level rise estimated from tide gauge records may have been overestimated.

Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay.

There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce "artificial" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as "scavenging" the reactive intermediate(s).

Comparative study of polyphenol scavenging activities assessed by different methods.

The effect of procyanidin solutions on superoxide anion radicals was studied with an enzymatic method and their EC(50) values were determined. A comparative study of the results suggested that the free radical scavenger potential of these phenolic compounds closely depends on their chemical and stereochemical structures. Oligomeric procyanidins were isolated in different fractions from grapes and wines by low- and high-pressure liquid chromatography. These compounds were found to be efficient free radical scavengers even for the weak concentrations in wines. Their activity in grapes or wines was much stronger than that of other commercially available natural antioxidants (such as ascorbic acid and gallic acid). The effect of tannins isolated from grapes on different radicals was analyzed according to three distinct methods: an enzymatic method for superoxide anion radicals (O(2)(*)(-)), a chemical method for the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH(*)), and an immunochemical method to study the scavenging activity of seed procyanidins on DNA lesions induced by the radical HO(*).

Ocean Tides for and from TOPEX/POSEIDON.

Comparisons of TOPEX/POSEIDON tidal solutions derived from the data of the first year of this altimetric mission with the best previous models and with in situ data show very substantial improvements. Typically, the gain in accuracy for the major lunar tidal component M(2) is 30 percent in root-mean-square differences with reference to a standard ground truth data set from 78 stations distributed over the world ocean. This is a major step, obtained because of the high quality of these altimetric data. The combination of these data with recent numerical models through assimilation methods is pointing toward solutions at the ultimate limits of practical accuracy.

Transparent oil-water gels.

Synopsis The present article reviews both the cosmetic and the pharmaceutical literature concerning transparent oil-water gels. We propose the term 'transparent oil-water gel' for semisolid systems that consist mainly of water, oil and an emulsifying agent or agents and that are characterized by a jelly-like consistency, transparency, homogeneity, optical isotropy, thermodynamic stability, and the occurrence of a 'ring' or resonance when a containerful is tapped. The literature reflects a rather remarkable degree of confusion, not only with regard to terminology, but also with regard to the basic concept of the formation of transparent oil-water gels. After a brief discussion justifying our selection of the term, the advantages specifically attributed to these gels are summarized, and the raw materials used in their formation as well as factors affecting their formulation are described. Finally, their applications as cosmetic and as pharmaceutical vehicles are reviewed.

The influence of emulsifiers on drug diffusion from o/w creams.

Histamine diffusion from various 0/w creams containing different emulsifiers was studied. To confirm the diffusion study, possible drug-emulsifier interactions were studied by dialysis of their aqueous solutions. Interactions between histamine and anionic sodium laurylsulphate resulted in the absence of free diffusible histamine. No interaction was observed with the non-ionic cetomacrogol. Repulsion by the cationic cetrimide increased histamine diffusion rate and total diffusing amount because distribution occurred in accordance with the Donnan membrane equilibrium.