Remyelination in vitro following protein kinase C activator-induced demyelination.

In previous work we found that mezerein, a C kinase activator, as well as basic fibroblast growth factor (FGF-2) induce demyelination and partial oligodendrocyte dedifferentiation in highly differentiated aggregating brain cell cultures. Here we show that following protein kinase C activator-induced demyelination, effective remyelination occurs. We found that mezerein or FGF-2 caused a transient increase in DNA synthesis following a pronounced decrease of the myelin markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase. Both oligodendrocytes and astrocytes were involved in this mitogenic response. Within 17 days after demyelination, myelin was restored to the level of the untreated controls. Transient mitotic activity was indispensable for remyelination. The present results suggest that myelinating oligodendrocytes retain the capacity to reenter the cell cycle, and that this plasticity is important for the regeneration of the oligodendrocyte lineage and remyelination. Although it cannot be excluded that a quiescent population of oligodendrocyte precursor cells was present in the aggregates and able to proliferate, differentiate and remyelinate, we could not find evidence supporting this view.

Footemineite, the Mn-analog of atencioite, from the Foote mine, Kings Mountain, Cleveland County, North Carolina, USA, and its relationship with other roscherite-group minerals

Footemineite, ideally Ca2Mn2+square Mn22+Be4(PO4)(6)(OH)(4)-6H(2)O, triclinic, is a new member of the roscherite group. It occurs on thin fractures crossing quartz-microcline-spodumene pegmatite at the Foote mine, Kings Mountain, Cleveland County, North Carolina, U.S.A. Associated minerals are albite, analcime, eosphorite, siderite/rhodochrosite, fairfieldite, fluorapatite, quartz, milarite, and pyrite. Footemineite forms prismatic to bladed generally rough to barrel-shaped crystals up to about 1.5 mm long and I mm in diameter. Its color is yellow, the streak is white, and the luster is vitreous to slightly pearly. Footemineite is transparent and non-fluorescent. Twinning is simple, by reflection, with twin boundaries across the length of the crystals. Cleavage is good on {0 (1) over bar1}) and {100}. Density (calc.) is 2.873 g/cm(3). Footemineite is biaxial (-), n(alpha) = 1.620(2), n(beta) = 1.627(2), n(gamma) = 1.634(2) (white light). 2V(obs) = 80 degrees, 2V(calc) = 89.6 degrees. Orientation: X boolean AND b similar to 12 degrees, Y boolean AND c similar to 15 degrees, Z boolean AND a similar to 15 degrees. Elongation direction is c, dispersion: r > v or r < v, weak. Pleochroism: beta (brownish yellow) > alpha = gamma (yellow). Mossbauer and IR spectra are given. The chemical composition is (EDS mode electron microprobe, Li and Be by ICP-OES, Fe3+:Fe2+ y Mossbauer, H2O by TG data, wt%): Li2O 0.23, BeO 9.54, CaO 9.43, SrO 0.23, BaO 0.24, MgO 0.18, MnO 26.16, FeO 2.77, Fe2O3 0.62, Al2O3 0.14, P2O5 36.58, SiO2 0.42, H2O 13.1, total 99.64. The empirical formula is (Ca1.89Sr0.03Ba0.02)Sigma(1.94)(Mn-0.90(2+)square(0.10))Sigma(1.00)(square 0.78Li0.17Mg0.05) Sigma(1.00)(Mn3.252+Fe0.432+ Fe0.093+Al0.03)Sigma(3.80) Be-4.30(P5.81Si0.08O24)[(OH)3.64(H2O)0.36]Sigma(4.00)center dot 6.00H(2)O . The strongest reflection peaks of the powder diffraction pattern [d, angstrom (1, %) (hkl)] are 9.575 (53) (010), 5.998 (100) (0 (1) over bar1), 4.848 (26) (021), 3.192 (44) (210), 3.003 (14) (0 (2) over bar2), 2.803 (38) ((1) over bar 03), 2.650 (29) ((2) over bar 02), 2.424 (14) (231). Single-crystal unit-cell parameters are a = 6.788(2), b = 9.972(3), c = 10.014(2) A, (x = 73.84(2), beta = 85.34(2), gamma = 87.44(2)degrees,V = 648.74 angstrom(3), Z = 1. The space group is P (1) over bar. Crystal structure was refined to R = 0.0347 with 1273 independent reflections (F > 2(5). Footemineite is dimorphous with roscherite, and isostructural with atencioite. It is identical with the mineral from Foote mine described as ""triclinic roscherite."" The name is for the Foote mine, type locality for this and several other minerals.

La circulación mercantil revelada por las guías de aduana de Buenos Aires, 1779-1783

Fil: Jumar, Fernando. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Los espacios portuarios : Un lugar de encuentro entre disciplinas

Tabla de contenidos: "Las villas nuevas" cantábricas en el marco de su primitiva organización territorial : Valles, alfoques, solares y linajes en los enclaves portuarios del litoral marítimo del reino de Castilla entre los siglos XII al XIV / Osvaldo Víctor Pereyra. El puerto Gaditano en el Inico del Ocaso de la Época Colonial [1810-1812] / Luis López Molina. Reflexiones sobre la incidencia del puerto en la vida de la ciudad de Montevideo / Arturo Ariel Bentancur. Los cargadores de cuero del Complejo Portuario Rioplatense / Maximiliano Camarda. El consulado de Buenos Aires y el quiebre de la Monarquía : Los préstamos y contribuciones de los comerciantes, 1808-1816 / Javier Kraselsky. Comercio, orden y derechos de propiedad de un puerto alternativo del Río de La Plata : La boca del Río Salado ebtre dos bloqueos [1838-1848] / Antonio Galarza. Entre el viento y el humo : Embarcaciones, puertos y tripulantes en la provincia de Buenos Aires en los primeros censos nacionales [1869-1914] / José Mateo, José Luis Nogueira. La cuestión del Muelle Nacional y reactivación de Arroyo Pareja / Gustavo Chalier. Génesis y desarrollo de la pesquería de camarón en el puerto de Mazatlán, 1949-1958 : El empresario como centro del engranaje productivo / Ulises Suárez Estavillo. Puertos y embarcaderos en la "Carrera de Paragua" (Siglo XVIII) / Isabel Paredes. La reactivación de los puertos del río Paraná en el discurso del desarrollismo antifrigerista, 1958-1976 / Miguel Angel De Marco. Redescubriendo la ruta hacia el norte : Del puerto de Buenos Aires a Potosí, en las postrimerías del siglo XVIII / María Claudia Errecart. Faenados a contravención : Decomisos de cueros en la Banda oriental durante 1784 y 1785 / Nicolás Biangardi. Fiscalidad en el Antiguo Régimen : Indagaciones en torno a la estructura fiscal del Virreinato del Río de La Plata. El caso de la Real Aduana de Buenos Aires [1776-1810] / María Evangelina Vaccani. La ruta del cacao : Circuito comercial de la élite pamplonesa, Virreinato de Nueva Granada, siglos XVIII-XIV / Lina Constanza Díaz Boada. El turismo como fenómeno económico, soail y cultural : Caso Mazatlán, México / Yasser Orlando Espinoza García, Héctor Manuel Pimienta Fernández. Delitos sexuales en el espacio portuario : Sexualidad y derecho en la encrucijada / Betina Clara Riva. La ciudad y el puerto : Transformaciones de áreas portuarias en desuso. El caso de puerto madero / Claudia Carut. Un Hada en La Boca : Imágenes post modernas de un puerto "inactivo! / Marcelo N. Weissel.

Na 1 Nachlass Max Horkheimer, 627 - Unterlagen zu den Vorlesungen "Über den Begriff der Seele seit Leibniz", "Einleitung in die Philosophie" und "Die Aufklärung" (p. VIII 45-VIII 47,1-2)

"Über den Begriff der Seele seit Leibniz" (GS 13, S. 515-569), Vorlesung Sommersemester 1958, Hilmar Tillack: Ausgearbeitete Nachschrift der Vorlesung von Max Horkheimer, Typoskript, 49 Blatt; "Einleitung in die Philosophie", Vorlesung Sommersemester 1959, Max Horkheimer: 1 Heft, eigene Notizen, 8 Blatt, davon 4 leer und 3 zusätzliche Blätter; Hilmar Tillack: Ausgearbeitete Nachschrift der Vorlesung Max Horkheimers, Typoskript 107 Blatt; "Die Aufklärung" (GS 13, S. 570-645), Vorlesung und Proseminar Wintersemester 1959/60, Max Horkheimer: eigenhändige Notizen, 1 Heft, 40 Blatt, davon 23 leer und 21 zusätzliche Blätter (GS 14, S. 146, 145-155); Hilmar Tillack: Ausgearbeitete Nachschrift der Vorlesung Max Horkheimers, Typoskript 70 Blatt;

Solid Lipid Nanoparticles For Hydrophilic Biotech Drugs: Optimization And Cell Viability Studies (caco-2 & Hepg-2 Cell Lines).

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.

Matrix metalloproteinase-2 polymorphism is associated with prognosis in prostate cancer

Objective: Prostate cancer (PCa) is the most frequent tumor in males in Brazil. Single nucleotide polymorphisms (SNP) have been demonstrated in the promoter region of matrix metalloproteinases (MMPs) genes and have been associated with development and progression of some cancers. In this study, our aim was to investigate a possible relation between polymorphism of the promoter region of the MMP2 gene and classical prognostic parameters in prostate cancer. Materials and methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction, using fluorescent probes (TaqMan). Results: In patients with tumors of a higher stage (pT3), a polymorphic allele in the MMP2 gene was more frequent (P = 0.026) than in patients with lower tumor stage. A polymorphic allele in the MMP2 gene was more frequent in Gleason >= 7 than in Gleason <= 6 (P = 0.042). Conclusions: We conclude that MMP2 polymorphism can be used together with pathological stage and Gleason score to identify patients with worse prognosis. Our results illustrate the potential use of MMP2 SNP as a molecular marker for prostate cancer. (C) 2010 Elsevier Inc. All rights reserved.

Can resistance to trastuzumab be reversed by endocrine therapy? Combination of trastuzumab and letrozole after resistance to sequential trastuzumab and aromatase inhibitor monotherapies in patients with ER-positive, HER-2 positive, advanced breast cancer: a proof-of-concept trial (SAKK 23/03)

Introduction: Trastuzumab (T) is a cornerstone in the treatment of patients with HER2-overexpressing advanced breast cancer and development of resistance to T is a major therapeutic problem. HER-2 is part of a highly interactive signaling network that may impair efficacy of endocrine therapy. A sequential treatment design was chosen in this trial to ensure complete resistance to single agent therapy before receiving both a non-steroidal aromatase inhibitor (AI) and T. Any kind of clinical activity with combined treatment of AI and T after progression of single agent treatments could indicate restoration of sensitivity as a consequence of cross-talking and networking between both pathways. Methods: Key eligibility criteria included postmenopausal patients (pts.) with advanced, measurable, HER-2 positive (assessed by FISH, ratio (≥2)), HR positive disease and progression on prior treatment with a non-steroidal AI, e.g. letrozole or anastrozole, either in an adjuvant or advanced setting. Pts. received standard dose T monotherapy either weekly or three-weekly in step 1 and upon disease progression, continued T in combination with letrozole in step 2. The primary endpoint was clinical benefit response (CBR: CR, PR or SD for at least 24 weeks (+/- 1 week) according to RECIST) in step 2. Results: Thirteen pts. were enrolled in five centers in Switzerland. In step 1, six pts. (46%) achieved CBR. Median time to progression (TTP) was 161 days (Range: 50 - 627). Based on data collected until the end of May 2010, CBR was observed in seven out of the eleven evaluable pts. (64%) in step 2, including one pt. with partial response. Four of the seven pts. within step 2 that achieved CBR also had CBR in step 1. Seven out of eleven pts. have documented tumor progression during step 2 treatment. Median TTP for all eleven pts. was 184 days (range 61 - 471). Mean time on study treatment (TTP in step 1 plus TTP in step 2) for pts. reaching step 2 was 380 days (range 174 - 864). Adverse events were generally mild. Conclusion: Results of this proof-of-principle trial suggest that complete resistance to both AI and T can be overcome in a proportion of pts. by combined treatment of AI and T, as all pts. served as their own control. Our results appear promising for a new treatment strategy which offers a chemotherapy-free and well-tolerated option for at least a subset of the pts. with HR positive, HER-2 positive breast cancer. Further trials will need to corroborate this finding.