Radio-resistance induced by nitric oxide to heavy ion irradiation in A172 human glioma cells

To investigate effects of nitric oxide on cellular radio-sensitivity, three human glioma cell lines, i.e. A172, A172 transfected green fluorescence protein (EGFP) gene (EA172) and A172 transfected inducible nitric oxide synthesis (iNOS) gene (iA72), were irradiated by C-12(6+) ions to 0, 1 or My. Productions of nitric oxide and glutathione (GSH) in A172, EA172 and iA172 were determined by chemical methods, cell cycle was analyzed by flow cytometry at the 24th hour after irradiation, and survival fraction of the cells was measured by colorimetric MTT assay at the 5th day after irradiation. The results showed that the concentrations of nitric oxide and GSH in iA172 were significantly higher than in A172 and EA172; the G(2)/M stage arrest induced by the C-12(6+) ion irradiation was observed in A172 and EA172 but not in iA172 at the 24th hour after exposure; and the survival fraction of iA172 was higher than that of EA172 and iA172. Data suggest that the radio-sensitivity of the A172 was reduced after the iNOS gene transfection. The increase of GSH production and the change of cellular signals such as the cell cycle control induced by nitric oxide may be involved in this radio-resistance.

Syntheses and properties of polyimides derived from diamines containing 2,5-disubstituted pyridine group

A Series of novel homo- and copolyimides containing pyridine units were prepared from the heteroaromatic diamines, 2,5-bis (4-aminophenyl) pyridine and 2-(4aminophenyl)-5-aminopyridine, with pyromelltic dianhydride (PMDA), and 3,3',4,4'-biphenyl tertracarboxylic dianhydride (BPDA) via a conventional two-step thermal imidizaton method. The poly(amic acid) precursors have inherent viscosities of 1.60-9.64 dL/g (c = 0.5 g/dL in DMAC, 30 degrees C) and all of them can be cast and thermally converted into flexible and tough polyimide films. All of the polyimides show excellent thermal stability and mechanical properties. The polyimides have 10% weight loss temperature in the range of 548-598 degrees C in air. The glass transition temperatures of the PMDA-based samples are in the range of 395-438 degrees C, while the BPDA-based polyimides show two glass transition temperatures (T(g)1 and T(g)2), ranging from 268 to 353 degrees C and from 395 to 418 degrees C, respectively. The flexible films possess tensile modulus in the range of 3.42-6.39 GPa, strength in the range of 112-363 MPa and an elongation at break in the range of 1.2-69%. The strong reflection peaks in the wide-angle X-ray diffraction patterns indicate that the polyimides have a high packing density and crystallinity.

Laser light-scattering study of novel thermoplastics .2. Phenolphthalein poly(ether sulfone) (PES-C)

Five narrowly distributed fractions of phenolphthalein poly(ether sulfone) (PES-C) were studied in CHCl3 by both static and dynamic laser light scattering (LLS) at 25 degrees C. The dynamic LLS showed that the PES-C samples contain some large polymer clusters as in previously studied phenolphthalein poly(ether ketone)(PEK-C). These large clusters can be removed by a 0.1-mu m filter. Our results showed that [R(g)(2)](1/2)(z) = (3.35 +/- 0.13) x 10(-2) M(w)((0.52 +/- 0.03)) and [D] = (2.26 +/- 0.02) x 10(-4)M(w)-((0.54) +/- 0.03)) with [R(g)(2)](1/2)(z), M(w) and [D] being the z-average radius of gyration, the weight-average molecular weight, and the z-average translational diffusion coefficient, respectively. A combination of static and dynamic LLS results enabled us to determine D = (2.45 +/- 0.04) x 10(-4)M-((0.55 +/- 0.05)), where D and M correspond to monodisperse species. Using this scaling relationship, we have successfully converted the translational diffusion coefficient distribution into the molecular weight distribution for each of the five PES-C fractional The weight-average molecular weights obtained from dynamic light scattering have a good agreement with that obtained from static laser light-scattering measurements.

二(2-乙基己基)膦酸萃取Er(Ⅲ)的动力学和机理

H(DEHP)是HEH(EHP)和HDEHP的同系物,它们的结构分别为:HDEHP,(GO)_2PO(OH);HEH(EHP),(GO)(G)PO(OH);H(DEHP),(G)_2PO(OH)。其中G为2-乙基已基。 希土元素萃取分离工艺化学表明,溶剂萃取希土元素对酸度的依赖关系及相邻希土元素间的分离因素值是选择萃取剂时应优先考虑的因素。HDEHP萃取剂对中、重希士元素反萃酸度高,HEH(EHP)是一个优良萃取剂,但对Er,Tm,Yb,Lu的反萃仍需5mol/l的酸。由于H(DEHP)分子中不含酯氧原子,使得它的pK_a值比HDEHP和HEH(EHP)的高。从而,用H(DEHP)萃取希土元素时需要的水相酸度更低,反萃更容易。而且H(DEHP)

Compromised Spindle Assembly Checkpoint due to Altered Expression of Ubch10 and Cdc20 in Human Papillomavirus Type 16 E6 and E7-Expressing Keratinocytes

Cells expressing human papillomavirus type 16 (HPV-16) E6 and E7 proteins exhibit deregulation of G(2)/M genes, allowing bypass of DNA damage arrest signals. Normally, cells with DNA damage that override the G(2) damage checkpoint would precociously enter mitosis and ultimately face mitotic catastrophe and apoptotic cell death. However, E6/E7-expressing cells (E6/E7 cells) have the ability to enter and exit mitosis in the presence of DNA damage and continue with the next round of the cell cycle. Little is known about the mechanism that allows these cells to gain entry into and exit from mitosis. Here, we show that in the presence of DNA damage, E6/E7 cells have elevated levels of cyclin B, which would allow entry into mitosis. Also, as required for exit from mitosis, cyclin B is degraded in these cells, permitting initiation of the next round of DNA synthesis and cell cycle progression. Proteasomal degradation of cyclin B by anaphase-promoting complex/cyclosome (APC/C) is, in part, due to elevated levels of the E2-conjugating enzyme, Ubch10, and the substrate recognition protein, Cdc20, of APC/C. Also, in E6/E7 cells with DNA damage, while Cdc20 is complexed with BubR1, indicating an active checkpoint, it is also present in complexes free of BubR1, presumably allowing APC/C activity and slippage through the checkpoint.

Estrogen Receptor-beta Affects the Prognosis of Human Malignant Mesothelioma

Malignant pleural mesothelioma is an asbestos-related neoplasm with poor prognosis, refractory to current therapies, the incidence of which is expected to increase in the next decades. Female gender was identified as a positive prognostic factor among other clinical and biological prognostic markers for malignant mesothelioma, yet a role of estrogen receptors (ERs) has not been studied. Our goal was to investigate ERs expression in malignant mesothelioma and to assess whether their expression correlates with prognosis. Immunohistochemical analysis revealed intense nuclear ER beta staining in normal pleura that was reduced in tumor tissues. Conversely, neither tumors nor normal pleura stained positive for ER alpha. Multivariate analysis of 78 malignant mesothelioma patients with pathologic stage, histologic type, therapy, sex, and age at diagnosis indicated that FRO expression is an independent prognostic factor of better survival. Moreover, studies in vitro confirmed that treatment with 17 beta-estradiol led to an ER beta-mediated inhibition of malignant mesothelioma cell proliferation as well as p21(CIP1) and p27(KIP1) up-regulation. Consistently cell growth was suppressed by ER beta overexpression, causing a G(2)-M-phase cell cycle arrest, paralleled by cyclin B1 and survivin down-regulation. Our data support the notion that ER beta acting as a tumor suppressor is of high potential relevance to prediction of disease progression and to therapeutic response of malignant mesothelioma patients. [Cancer Res 2009;69(11):4598-604]

Evidence for the presence of G-proteins, adenylyl cyclase and phospholipase C activities in lymphatic smooth muscle cell membranes

In plasma membranes derived from bovine mesenteric lymphatic smooth muscle cells, guanine nucleotide and forskolin stimulated adenylyl cyclase (AC) activity in a concentration-dependent manner, indicative of the presence of the stimulatory G-protein G(s) linked to AC. There was no significant enzyme inhibition by low concentrations of guanine nucleotide and no effect on basal or guanine nucleotide-stimulated activity following pertussis toxin treatment of cells, suggesting the absence of G(1) linked to inhibition of AC. Furthermore, there was no effect of adrenaline, isoprenaline or clonidine on basal or forskolin-stimulated activities, nor was there any specific binding of the beta-adrenoceptor ligand [I-125]cyanopindolol to membranes, suggesting that cate-cholamine receptors do not modulate AC activity in these membranes. Pertussis toxin-mediated ADP ribosylation of membrane proteins and Western immunoblotting analysis revealed the presence of G-protein subunits G(alpha l2), G(alpha q), G(alpha 11) and G(beta 1). In experiments designed to identify a possible effector enzyme for these G-proteins, membranes were screened with a range of antibodies raised against phospholipase C (PLC) beta, gamma and delta isozymes. Though no evidence was obtained by Western blotting for any of these proteins, PLC activity was concentration-dependently stimulated by Ca2+, but not by AlF4-, GTP[S], or purified G(beta gamma) subunits. Finally, no specific binding to membranes of the alpha(1)-adrenoceptor ligand [H-3]prazosin or the alpha(2)-adrenoceptor ligand [H-3]yohimbine was obtained. In conclusion, this study provides evidence for a G(s)-dependent stimulation of AC, and for the presence of G(2) and G(q11), which do not appear to regulate a PLC activity also identified in lymphatic smooth muscle cell membranes. Furthermore, neither AC nor PLC appear to be associated with catecholamine receptors. Copyright(C) 1996 Elsevier Science Inc.

The vascular targeting agent combretastatin-A4 and a novel cis-Restricted {beta}-Lactam Analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells and ex vivo patient samples including those displaying multidrug resistance

Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree Combretum caffrum. CA-4 is one of the most potent antimitotic components of natural origin, but it is, however, intrinsically unstable. A novel series of CA-4 analogs incorporating a 3,4-diaryl-2-azetidinone (β-lactam) ring were designed and synthesized with the objective to prevent cis -trans isomerization and improve the intrinsic stability without altering the biological activity of CA-4. Evaluation of selected β-lactam CA-4 analogs demonstrated potent antitubulin, antiproliferative, and antimitotic effects in human leukemia cells. A lead β-lactam analog, CA-432, displayed comparable antiproliferative activities with CA-4. CA-432 induced rapid apoptosis in HL-60 acute myeloid leukemia cells, which was accompanied by depolymerization of the microtubular network, poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Bcl-2 cleavage. A prolonged G(2)M cell cycle arrest accompanied by a sustained phosphorylation of mitotic spindle checkpoint protein, BubR1, and the antiapoptotic proteins Bcl-2 and Bcl-x(L) preceded apoptotic events in K562 chronic myeloid leukemia (CML) cells. Molecular docking studies in conjunction with comprehensive cell line data rule out CA-4 and β-lactam derivatives as P-glycoprotein substrates. Furthermore, both CA-4 and CA-432 induced significantly more apoptosis compared with imatinib mesylate in ex vivo samples from patients with CML, including those positive for the T315I mutation displaying resistance to imatinib mesylate and dasatinib. In summary, synthetic intrinsically stable analogs of CA-4 that display significant clinical potential as antileukemic agents have been designed and synthesized.

Dual targeting of tumour cells and host endothelial cells by novel microtubule-targeting agents, pyrrolo-1,5-benzoxazepines

PURPOSE: Some members of a novel series of pyrrolo-1,5-benzoxazepines (PBOXs) are microtubule-targeting agents capable of inducing apoptosis in a variety of human cancerous cells, hence, they are currently being developed as potential anti-cancer agents. The purpose of this study was to first characterise the activities of a novel PBOX analogue, PBOX-16 and then investigate the anti-angiogenic potential of both PBOX-16 and its prototype PBOX-6.

METHODS: The effects of PBOX-6 and -16 on cancerous cells (chronic myeloid leukaemia K562 cells and ovarian carcinoma A2780 cells) and primary cultured human umbilical vein endothelial cells (HUVECs) were examined by assessing cell proliferation, microtubular organisation, DNA analysis of cell cycle progression and caspase-3/7 activity. Their anti-angiogenic properties were then investigated by examining their ability to interfere with HUVEC differentiation into capillary-like structures and vascular endothelial growth factor (VEGF)-stimulated HUVEC migration.

RESULTS: PBOX-6 and -16 inhibited proliferation of K562, A2780 and HUVEC cells in a concentration-dependent manner. PBOX-16, confirmed as a novel depolymerising agent, was approximately tenfold more potent than PBOX-6. Inhibition of cell proliferation was mediated by G(2)/M arrest followed by varying degrees of apoptosis depending on the cell type; endothelial cells underwent less apoptosis than either of the cancer cell lines. In addition to the antitumourigenic properties, we also describe a novel antiangiogenic function for PBOXs: treatment with PBOXs inhibited the spontaneous differentiation of HUVECs into capillary-like structures when grown on a basement membrane matrix preparation (Matrigel™) and also significantly reduced VEGF-stimulated HUVEC migration.

CONCLUSION: Dual targeting of both the tumour cells and the host endothelial cells by PBOX compounds might enhance the anti-cancer efficacy of these drugs.

Testing two different doses of tiotropium Respimat® in cystic fibrosis: Phase 2 randomized trial results

Background: Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 μg once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis. Methods: This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV₁) ≥25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV₁area under the curve from 0 to 4 hours (FEV₁AUC_0-4h), and trough FEV₁at the end of week 12. Findings: A total of 510 subjects with cystic fibrosis aged 5-69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV₁AUC_0-4h: 2.5 μg: 2.94%, 95% confidence interval 1.19-4.70, p = 0.001; 5 μg: 3.39%, 95% confidence interval 1.67-5.12, p = 0.0001; in percent-predicted trough FEV₁:2.5 μg: 2.24%, p = 0.2; 5 μg: 2.22%, p = 0.02). There was a greater benefit with tiotropium 5 vs. 2.5 μg. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium. Conclusions: Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events.

[Lettre autographe signée d'A. G. André à Camille Du Locle (sans date)]

Problèmes pour des loges demandées pour la Messe de Requiem

« Recueil de plusieurs procez criminels qui ne sont point imprimez ».

Contient : 1 « Procès criminel fait à messire Gilles de Rays, marechal de France, condamné et executé à mort en l'année 1440, au mois de septembre » ; 2 ; « Arrest prononcé contre sire Jacques Coeur à Lezignan, le 29e jour de may 1453 » ; « Revision du procès demandé par Jean Coeur, archevêque de Bourges, pretendant son père estre clerc, qui contient les appellations du patriarche et evêque de Poitiers et ses vicaires, et aussy dudit archevêque de Bourges contre les griefs faits à l'Eglise en la personne dudit Jacques Coeur ». 1453 ; 3 « Arrest du parlement contre le duc de Lorraine » Charles Ier « et ses complices, pour plusieurs pilleries, meurtres et autres crimes et delits ». 1412 ; 4 « Question si le roy peut estre interrogé et examiné en fait de crimes » ; 5 « Plaintes et poursuites faites en la cour de parlement contre le chancelier Du Prat, et les lettres escrittes par laditte cour à madame la regente » Louise de Savoie « et aux pairs de France, pour se trouver en laditte cour. En 1525 ». Juillet-septembre ; 6 « Arrêt rendu contre messire Guillaume Poyet, chancelier de France, Mre Jean de Royer, conseiller en châtelet, et Louis Martine, substitut du procureur du roy aud. châtelet, du 24 avril 1545, en la salle de Saint Louis » ; 7 « Arrest d'innocence de monsieur l'amiral de Châtillon » Gaspard de Coligny, « de la mort de monsieur de Guise », François de Lorraine. 1567 ; 8 « Histoire memorable de la très damnable conjuration faite par Charles Ridicauve d'attenter à la personne du... roy [Henri IV], fidellement extraite des actes du procès ». 1599 ; 9 Récit du procès, condamnation et exécution du duc de Biron. 1602 ; 10 « Discours sur la conspiration » contre le roi Henri IV de Henriette de Balsac, marquise de Verneuil, et du comte d'Auvergne (Charles de Valois, fils naturel de Charles IX et de Marie Touchet), frère utérin de ladite marquise. 1604-1605 ; 11 Interrogatoires faits à François Ravaillac, assassin de Henri IV, et relation de ce qui se passa lors de l'exécution à mort dudit Ravaillac. 1610 ; 12 « Arrest de la cour contre Jean Particelly, banqueroutier et faussaire, et autres complices ». 1620 ; 13 « Relation des particularités plus remarquables arrivées, tant à l'instruction du procès de messieurs de Sainct Mars et de Thou, qu'à leur mort ». 1642 ; 14 « Documents concernant l'affaire du cardinal de Bouillon et l'histoire généalogique de la maison d'Auvergne ; a Lettre dudit cardinal EMMANUEL THEODOSE DE LA TOUR D'AUVERGNE au roi Louis XIV. Arras, 22 mai 1710 ; b Lettre du même à M. le président de Maisons, Claude de Longueil. 25 juin 1710 ; c Lettre de LOUIS XIV au cardinal de La Trémoille. 26 mai 1710 ; d Réponse d'un anonyme à la lettre anonyme du cardinal de Bouillon au président de Maisons ; e Arrêt du conseil d'État du roi contrel' « Histoire genealogique de la maison d'Auvergne » par Etienne Baluze. Versailles, 1er juillet 1710 ; f « Declaration du roi concernant la disposition des bénéfices qui sont à la nomination du cardinal de Bouillon ». Versailles, 7 juillet 1710. Pièce imprimée ; g « Arrest du conseil et lettres patentes sur icelluy, portant qu'il sera pourvu par le parlement de Paris à la régie et administration de tous les biens, fruits et revenus du cardinal de Bouillon. Des 7 et 15 juillet 1710. Registrez en parlement le 30 juillet 1710 ». Pièce imprimée ; h Arrêt de la cour pour la destruction du mausolée que le cardinal de Bouillon avait fait faire dans l'église de Cluny. 2 janvier 1711 ; i « Memoire en faveur de monsieur le cardinal de Bouillon ». Ce mémoire, copie d'un imprimé annoncé comme se vendant à Tournay et daté de 1710, se compose : 1° d'un avis au lecteur ; 2° du texte (commenté dans le sens de la défense dudit cardinal) de la requête du procureur général au parlement de Paris H. F. d'Aguesseau, en date du 28 mai 1710, contre le cardinal ; 3° du commentaire de l'arrêt du même parlement, rendu le 20 juin 1710, portant prise de corps contre le cardinal et contre le père de Monthiers et le chevalier de Serte ; j « Memoire sur l'« Histoire genealogique de la maison d'Auvergne ». Dans une note qui précède ce titre, on lit que « ce memoire a esté copié sur l'original de Mr SORIN, qui a examiné par ordre de M. le chancelier la nouvelle edition de l'« Histoire genealogique de La Tour d'Auvergne », composée par monseigneur Baluze, laquelle edition a esté suprimée et mise au pilon par arrest du conseil » ; k « Copie d'un Receuil imprimé de quelques lettres escrites » depuis « le 14 de juin 1709 jusqu'au 24 de may 1710, concernant Son Altesse Eminentissime le cardinal de Bouillon, doyen du sacré collège, etc. 1710 ». Ce recueil contient : (pages 891-895) un « Avis au lecteur », daté du 1er juillet 1710 ; (pages 895-896) « lettre du marquis DE TORCY, ministre et secretaire d'Estat de France, au cardinal de Bouillon, doyen du sacré collège », datée de « Marly, ce 14 juin 1709 » ; (pages 896-900) « lettre du cardinal DE BOUILLON au marquis de Torcy », datée d'« Orléans, le 8 mars 1710 » ; (pages 900-903) lettre faisant suite à la précédente du même au même, datée d'« Orléans, le 9 mars 1719 » ; (pages 903-904) « route que le cardinal de Bouillon tiendra d'Orleans pour aller habiter les environs de Rouen, dans le present mois de mars 1710 » ; (pages 904-906), lettre du même cardinal au marquis de Torcy, datée d'« Orléans, le 8 mars 1710 » ; (pages 906) « lettre du marquis DE TORCY au cardinal de Bouillon, à Versailles, le 11 mars 1710 » ; (pages 907-908) « lettre du cardinal DE BOUILLON au marquis de Torcy », datée d' « Ormesson, ce jeudy 3 avril 1710 » ; (pages 908-909) lettre dudit cardinal au marquis de Torcy, datée d' « Arras, le 22 de may 1710 » ; (pages 909-912) « lettre escrite de Tournay, le 24 may 1710 », relative aux honneurs rendus par le prince Eugène et le duc de Marlborough au cardinal de Bouillon, à son passage au milieu des troupes de l'armée des alliés, le dit cardinal se rendant de l'abbaye de Saint Riquier près d'Abbeville, à l'abbaye de Vicoigne près Valenciennes, mais pour le moment arrêté à Tournay

Modelo de evaluación aplicado al currículum de Biología de la carrera de Agronomía en la Escuela Internacional de Agricultura y Ganadería (E.I.A.G.) de Rivas, Nicaragua.

1.- Ofrecer un modelo de evaluación para el currículum de Biología que permita la valoración de su funcionalidad, eficiencia y eficacia en la formación de Técnicos Superiores en Agronomía a través de un análisis reflexivo y crítico de la realidad educativa. 2.- Proponer la evaluación del Currículum de Biología como alternativa a la mejora de la calidad de los procesos de enseñanza-aprendizaje que permitan respaldar los procesos de desarrollo nacional. 3.- Contribuir a la autonomía y toma de decisiones del docente utilizando un modelo de evaluación adaptado al contexto de la educación agrícola y que permita el conocimientos de los valores, características, posibilidades y necesidades que identifican. Treinta y tres sujetos: el director del Instituto de Bachillerato, la profesora de Biología de COU, 30 alumnos del curso de COU y el Coordinador de Biología de los COU de Salamanca. El modelo utilizado para la evaluación del currículo de Biología es el modelo CIPP (contexto, entrada, proceso, producto) de Stufflebeam, integrando las aportaciones y valoraciones de la Dra. Margarita Bartolomé Pina. Entrevistas semiestructuradas con los participantes y observación participante. Análisis arbóreo funcional y triangulación. La investigación realiza una propuesta de evaluación del currículum de Biología, del Plan de estudios de la carrera de Agronomía en la Escuela Internacional de Agricultura y Ganadería de Rivas, eligiendo el modelo CIPP de Stufflebean. Para probar el modelo se aplica el mismo a los alumnos de Biología de un Instituto de Bachillerato de Salamanca con el objeto de realizar los ajustes necesarios sobre el modelo para posteriormente poderlo aplicar en los estudios de Agronomía de la facultad de Rivas, en Nicaragua. El estudio realizado fue de 6 días, tiempo brevísimo para obtener resultados fiables y válidos, pero adecuado para familiarizarse con la aplicación del modelo, a la vez que conocer la realidad educativa española. Se consiguió un ambiente adecuado de trabajo donde se desarrolló adecuadamente el proceso. La aplicación parcial del modelo CIPP al currículum de Biología de un grupo de alumnos de un Instituto de Bachillerato de Salamanca se deducen las siguientes relaciones entre las diferentes categorías: el contexto, la entrada, el proceso y el producto. El contexto donde se desarrolla la acción educativa es adecuado, las instalaciones son adecuadas para la tarea. La elaboración del currículo de Biología no parte de las necesidades del alumnado, sino que parte de las propuestas del MEC en estrecha relación con el programa de Biología de la Universidad, es elaborado por el coordinador de Biología de los COU de Salamanca en colaboración con el profesorado que imparte esta materia. La ventaja que ofrece el currículum es la adecuación a la realidad científica contextual, adecuándolo a los cambios propios del medio y utilizando los recursos necesarios; los problemas aparecen en la vinculación de la teoría y la práctica. Durante el proceso se debería informar al alumno de la utilidad de cada uno de los temas y los objetivos que se persiguen para incrementar la motivación y expectativas. Durante el proceso es importante que el Director del Centro y el Coordinador de los COU realicen un seguimiento al desarrollo del currículo para buscar alternativas de solución de problemas. El último producto de la enseñanza debe ser la satisfacción de haber formado hombres y mujeres críticos y creativos que respondan a las demandas de la sociedad. De los resultados obtenidos en la aplicación del modelo CIPP en el centro educativo español, puede extraerse las siguientes conclusiones en su extrapolación al contexto nicaragüense al currículo de Biología de la carrera de Agronomía: 1.- La evaluación ha de partir del estudio exhaustivo sobre la realidad educativa de la E.I.A.G. 2.- La evaluación ha de ser práctica y se han de obtener los datos necesarios en el tiempo estipulado. 3.- Se ha de prestar atención a la influencia ejercida por los directivos y docentes, para modificar los resultados a su favor una vez realizada la evaluación. 4.- Las entrevistas dirigidas hacia el alumnado serán de fácil comprensión, para que puedan responder a las diferentes cuestiones; se les presentará los resultados de las mismas para su análisis. 5.- Se tratará de aplicar la evaluación con los menores costes posibles, atendiendo a los presupuestos asignados por la administración. 6.- La aplicación del Modelo CIPP de evaluación del currículum de Biología de la E.I.A.G. deberá permitir la extrapolación o adecuación del modelo a la evaluación de otras materias y a la evaluación del centro de manera integral.