Differential expression of p120 catenin in glial cells of the adult rat brain

p120 catenin (p120ctn) is involved in the regulation of cadherin-mediated adhesion and the dynamic organization of the actin cytoskeleton by modulating RhoGTPase activity. We have previously described the distribution of p120ctn during rat brain development and provided substantial evidence for the potential involvement of p120ctn in morphogenetic events and plasticity in the central nervous system. Here, we analyzed the cellular and ultrastructural distribution of p120ctn in glial cells of the adult rat forebrain. The highest intensity of immunostaining for p120ctn was found in cells of the choroid plexus and ependyma and was mainly restricted to the plasma membrane. However, p120ctn was almost absent from astrocytes. In contrast, in tanycytes, a particular glial cell exhibiting remarkable morphological plasticity, p120ctn, was localized at the plasma membrane and also in the cytoplasm. We show that a large subpopulation of oligodendrocytes expressed multiple isoforms, whereas other neural cells predominantly expressed isoform 1, and that p120ctn immunoreactivity was distributed through the cytoplasm and at certain portions of the plasma membrane. Finally, p120ctn was expressed by a small population of cortical NG2-expressing cells, whereas it was expressed by a large population of these cells in the white matter. However, in both regions, proliferating NG2-positive cells consistently expressed p120ctn. The expression of p120ctn by cells of the oligodendrocyte lineage suggests that p120ctn may participate in oligodendrogenesis and myelination. Moreover, the expression of p120ctn by various cell types and its differential subcellular distribution strongly suggest that p120ctn may serve multiple functions in the central nervous system.     

Glucose-receptor MR imaging of tumors: study in mice with PEGylated paramagnetic niosomes

PURPOSE: To evaluate a magnetic resonance (MR) imaging contrast agent for tumor detection based on paramagnetic nonionic vesicles (niosomes) bearing polyethylene glycol (PEG) and glucose conjugates for the targeting of overexpressed glucose receptors. MATERIALS AND METHODS: Four gadobenate dimeglumine-loaded niosome preparations including nonconjugated niosomes, niosomes bearing glucose conjugates (N-palmitoyl glucosamine [NPG]), niosomes bearing PEG 4400, and niosomes bearing both PEG and NPG were tested. In vitro cellular uptake was measured at electron paramagnetic resonance (EPR) after incubation with human prostate carcinoma, PC3, cells. In vivo distribution was studied at MR imaging 6, 12, and 24 hours after injection, with assessment of tumor, brain, liver, and muscle signal intensity (SI) in 49 mice bearing PC3 cells. Efficiency of targeted contrast agents was assessed with tumor-to-muscle contrast-to-noise ratio (CNR). Testing for differences was performed with analysis of variance followed by a posteriori Fisher test. RESULTS: In vitro, gadolinium could be detected at EPR only in cell pellets incubated with niosomes bearing glucose conjugates or niosomes bearing both glucose conjugates and PEG (4.9. 10(-15) and 4.5. 10(-15) mol gadolinium per PC3 cell). In vivo, marked predominant tumor enhancement was demonstrated 24 hours after injection of glycosylated PEG niosomes (P <.01); no significant differences were observed following injection of nonconjugated niosomes, glycosylated niosomes, or PEG 4400 niosomes. Twenty-four hours after injection, sole presence of NPG or PEG 4400 on the surface of the niosome led to higher tumor-to-muscle CNR than that observed after injection of nonconjugated niosomes (CNR of 3.3 +/- 0.7 [SD], 3.4 +/- 2.2, and 0 +/- 1.9). Combination of NPG and PEG led to even higher tumor-to-muscle CNR (6.3 +/- 2.2). CONCLUSION: Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.     

Effect of magnesium on mechanical properties of pressurized mesenteric small arteries from old and adult rats

The purpose of the present study was to determine the effects of magnesium (Mg) on the mechanical properties of resistance arteries in adult and old rats. Studies were performed in adult (17 weeks) and old (104 weeks) male Wistar rats. The vasodilatory response and the passive mechanical properties of the wall of isolated perfused and pressurized arterial segments of mesenteric small arteries were investigated after Mg and verapamil application, both known for their calcium antagonistic properties. Mesenteric resistance arteries from old rats exhibited an outward hypertrophic remodelling, with enlargment of the lumen, thickening of the media and enlarged media cross-sectional area. The vasodilatory response induced by the application of increasing extracellular concentrations of Mg and verapamil was significantly smaller in preconstricted mesenteric arteries of old rats than in those of adult rats. Incremental distensibility in response to increasing intravascular pressures did not change. However, the stress-strain curve was shifted to the left in pressurized mesenteric arteries from old rats, indicating arterial wall stiffness. Verapamil (3 micro mol/L) did not modify the stress-strain curves in either adult or aged rats. However, Mg (4.8 mmol/L) significantly shifted the curve to the right in mesenteric arteries from adult rats and, to a greater degree, in those from old rats. Although Mg-induced vasodilatation is impaired in aged rats, increased Mg concentration improved the mechanics of pressurized mesenteric resistance arteries. The fact that Mg decreases arterial stiffness in arteries from old rats suggests that Mg has a beneficial effect on age-related changes to the vascular wall.     

Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin administration: comparative results with cisplatin using a rabbit VX2 tumor model

The aim of this study was to compare intra-arterial hepatic administration (IAH) versus i.v. administration of oxaliplatin and cisplatin in a VX2 tumor model in rabbits. VX2 tumors were implanted in the livers of White New Zealand female rabbits and 2 weeks later they received either cisplatin (4 mg/kg) or oxaliplatin (6 mg/kg) administered by IAH or i.v. Platinum pharmacokinetic parameters were measured by atomic absorption spectrometry at baseline, 2, 5 10, 20, 40 and 60 min, and then at 2, 4, 6 and 24 h after drug administration. Animals were sacrificed 24 h after drug administration to measure platinum concentrations in various tissues. After IAH oxaliplatin administration, we observed a significant decrease for total and filterable platinum in the Cmax compared with i.v. administration (12.4 versus 18.2 microg/l; p=0.02 and 11.2 versus 17.3 microg/l; p=0.02, respectively). Significant differences in various tissue concentrations were reported when comparing IAH and i.v. administration of oxaliplatin with IAH administration offering an advantage over i.v. administration. No differences in pharmacokinetic parameters or platinum tissue accumulation were apparent between the IAH and i.v. administration with cisplatin. We conclude that there is a significant pharmacokinetic advantage to using oxaliplatin for locoregional IAH chemotherapy compared with i.v. administration.     

Clinical characteristics of acute HSV-2 retinal necrosis

PURPOSE: To report the clinical features and evaluate the visual outcome of eleven cases of herpes simplex virus-2 (HSV-2) related acute retinal necrosis syndrome (ARN). DESIGN: Retrospective interventional case series. METHODS: Twelve eyes of eleven patients from two European centers, diagnosed with HSV-2 related acute retinal necrosis syndrome were retrospectively reviewed. Herpes simplex virus-2 DNA was detected by polymerase chain reaction in intraocular fluids (aqueous and/or vitreous). Findings at initial examination, clinical evolution with antiviral therapy, complications and final visual acuity were evaluated. RESULTS: Herpes simplex virus-2 DNA was detected in all cases. No sample was positive for more than one virus. The mean age of disease in the first eye was 36 years (ranged from 10 to 57 years). Five patients were women and six were men. All patients were immunocompetent. Previous medical history included neonatal herpes (n = 1), previous ARN (n = 3), trauma (n = 1) and systemic corticosteroid administration before occurrence of ARN (n = 3). Preexisting pigmented chorioretinal scars were found in three cases. Patients were treated with high dose intravenous acyclovir or foscarnet +/- intravitreal ganciclovir +/- interferon. The mean follow-up was 14.5 months (from 5 to 22 months). At the end of the follow-up period, five eyes (41.7%) showed improvement of visual acuity of two or more lines. Final visual acuity was 20/60 or better in four eyes (33.3%), 20/400 or better in four eyes (33.3%) and less than 20/400 in four eyes. CONCLUSION: History of neonatal herpes, triggering events such as neurosurgery, periocular trauma, high-dose corticosteroids, and chorioretinal scars suggest that HSV-2 retinitis reflects reactivation of HSV-2 infection.     

Dysmorphology and the orbital region: a practical clinical approach

Dysmorphology is the field of medicine focusing on congenital developmental abnormalities due to exogenous teratogens, chromosomal anomalies, or to a defect in a single gene. Numerous syndromes have been reported and a growing number of genes or chromosomal anomalies are identified. The clinical observation of the face remains an essential part of the clinical evaluation of the patients. The orbital region, as other regions of the face, should be systematically evaluated. Orbital malformations can be isolated or part of a syndrome. In the diagnostic process, the orbital anomaly can be classified as a major feature (essential for the diagnosis), a moderate feature (important but not essential for the diagnosis), or a minor feature (contributing weakly to the diagnosis). The diagnoses of the main orbital anomalies in dysmorphology are reviewed and illustrated with relevant examples of syndromes that are presented as well as the usual landmarks used in clinical practice. Abnormal position of the eyes in syndromes such as hypertelorism, hypotelorism, primary or secondary telecanthus, asymmetry, and proptosis are discussed. Eyelid anomalies, such as cryptophthalmos, ablepharon, blepharophimosis, euryblepharon, or anomalies at the level of the eyelashes and eyebrows are described.     

Structural requirements of the N-terminal region of GLP-1-[7-37]-NH2 for receptor interaction and cAMP production

A series of GLP-1-[7-36]-NH(2) (tGLP-1) and GLP-1-[7-37] analogs modified in position 7, 8, 9 and 36, have been designed and evaluated on murine GLP-1 receptors expressed in RIN T3 cells for both their affinity and activity. Ten of the synthesized peptides were found full agonists with activities superior or at least equal to that of the native hormone. Five of them were investigated for their plasmatic stability and the most stable, [a(8)-desR(36)]GLP-1-[7-37]- NH(2) (Compound 8), evaluated in vivo in a glucose tolerance test which confirmed a clearly longer activity than that of the native hormone. We also performed circular dichroism study and propose a hypothetical structural model explaining the most part of observed activities of GLP-1 analogs on RIN T3 cells.