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Evaluación de la oportunidad de inmovilización de un activo: Un estudio de caso para una microempresa del ramo de tecnologia de información aplicada a la construcción civil RESUMEN El propósito de este artículo es analizar la posibilidad de inmovilización de inmuebles corporativos, teniendo en cuenta las expectativas de los usuarios corporativos de los inmuebles. Para ello, optamos por realizar el estudio de caso con una micro empresa en el sector de tecnologías de la información la construcción civil. Por lo tanto, fueron evalúdas las oportunidades y las alternativas: compra de bienes inmuebles, alquiler de corto plazo, alquiler de largo plazo y la construcción a la medida. El método de toma de decisiones utilizado fue de analisis jerárquico, ya que esta incluye criterios de decisión cualitativa y cuantitativa relevantes para la elección entre las distintas alternativas. El resultado final del análisis es la recomendación de la alternativa de elección, que mejor atienda principales por las partes interesadas. Palabras clave: inmovilización; la desmovilización; inmuebles corporativos; análisis jerárquico. Evaluation of an active immobilizing opportunity: A case study for a micro-enterprise information technology branch applied to construction ABSTRACT The purpose of this article is the analysis of immobilizing opportunity to corporate real estate, taking into account the expectations of users of real estate corporations. For this, we chose the case study with a micro branch of information technology applied to construction. Thus, the purchase opportunities and alternatives were evaluated: a short-term lease, long-term lease and built-to-suit. The method of decision-making was hierarchical analysis; it contemplates decision criteria, qualitative and quantitative, relevant to the choice between the alternatives. The result of the analysis is to provide a recommendation of choice alternatives, starting from the one that best meets the criteria prioritized by stakeholders. Keywords: immobilization; demobilization; real estate; analytic hierarchy process. Avaliação da oportunidade de imobilização de um ativo: Um estudo de caso para uma microempresa do ramo de tecnologia de informação aplicada à construção civil RESUMO O objetivo deste artigo é analisar a oportunidade de imobilização de imóveis corporativos, considerando as expectativas das corporações usuárias dos imóveis. Para isto, optou-se pela realização de estudo de caso com uma microempresa do ramo de tecnologia de informação aplicada à construção civil. Assim, foram avaliadas as oportunidades e as alternativas: compra do imóvel, a locação de curto prazo, a locação de longo prazo e o built-to-suit. O método de tomada de decisão utilizado foi o da análise hierárquica, pois esta contempla critérios de decisão qualitativos e quantitativos relevantes à escolha entre as diferentes alternativas. O resultado final da análise é a recomendação da alternativa de escolha, que melhor atende aos critérios priorizados pelas partes interessadas. Palavras-chave: imobilização; desmobilização; imóveis corporativos; análise hierárquica.

A homotransplantable tumour (LY) and cell lines (LY-PPB6 and LY-H12) were established from a spontaneous malignant peripheral nerve sheath tumour (PNST) of the uterine cervix of an F344 rat. Primary and LY tumours consisted of oval or spindle-shaped cells arranged in a flatfield or streaming fashion, and indistinct nuclear palisades were seen. Immunohistochemically, neoplastic cells reacted to vimentin, S-100 protein, neuron-specific enolase (NSE), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) in varying degrees, indicating neurogenic derivation. LY-PPB6-induced tumours in syngeneic rats developed cellular whorling patterns reacting particularly strongly to S-100 protein, NSE, MBP and GFAP. Nerve growth factor (NGF) mRNA expression was shown in LY-PPB6 cells by the reverse transcription-polymerase chain reaction (RT-PCR). By contrast, LY-H12 had a normal chromosomal number of 42, and did not produce tumours when injected into syngeneic rats. LY-H12 cells reacted to vimentin and alpha-smooth muscle actin (alpha-SMA), and the alpha-SMA-positive cell number was increased dose-dependently by the addition of transforming growth factor (TGF)-beta1, indicating a myofibroblastic nature. LY-PPB6 cells were neoplastic with properties of PNS cells, whereas LY-H12 cells were non-neoplastic stromal cells showing myofibroblastic differentiation. As TGF-beta1 mRNA expression was shown in both LY-PPB6 and LY-H12 cells by the RT-PCR, the myofibroblastic phenotype of LY-H12 cells may be mediated by paracrine or autocrine signalling in tumour tissues. LY-PPB6 and LY-H12 may prove useful for studies on the pathobiological nature of neoplastic cells and interactions between neoplastic and stromal cells in PNSTs.

In order to clarify whether the ovarian tumors induced in a long-term carcinogenicity study of nitrofurazone (NF) in mice can be also produced in a short-term model using transgenic (Tg) mice carrying the human c-Ha-ras gene (rasH2 mice), the following 3 experiments were performed. In experiment 1, both rasH2 mice and their wild CB6F1 littermates carrying no c-Ha-ras gene (non-Tg mice) that were fed a diet containing 500 to 1,000 ppm NF for 7 weeks demonstrated ovarian atrophy characterized by decreased labeling indices (LIs) for proliferating cell nuclear antigen (PCNA) in granulosa cells. In experiment 2, increased numbers of atretic follicles and decreased PCNA LIs in granulosa cells were recognized in rasH2 mice given diets containing 250 or 500 ppm NF for 26 weeks, but no tumor induction was grossly observed. In experiment 3, similar ovarian atrophy was observed in association with increased serum luteinizing hormone (LH) levels in both rasH2 and non-Tg mice given diet containing 1,000 ppm NF for 11 days. These results indicate that long-term NF treatment induces ovarian tumors in mice, possibly by continuous stimulation with gonadotropins such as LH via a negative-feedback phenomenon secondary to ovarian atrophy (as the tumor-induction mechanism), although we could not completely rule out a genotoxic mechanism.

In our previous investigation, which focused on two-stage carcinogenicity in the thyroid, rats were administered N-bis(2-hydroxypropyl)nitrosamine (DHPN), followed by thiourea (TU) over an experimental period of 19 weeks. Simultaneous treatment with a high level of vitamin A (VA) enhanced the induction of proliferative lesions that originated from the thyroidal follicular epithelium. To examine whether hormone synthesis in the thyroid could be inhibited by simultaneous treatment with a large amount of VA and TU, all of the rats were initially given a single subcutaneous injection of 2,800 mg DHPN/kg followed by a supply of 0% TU + 0% VA (DHPN only, control group), 0.2% TU in their drinking water (DHPN/TU group), 0.1% VA in their diet (DHPN/VA group), or 0.2% TU + 0.1% VA (DHPN/TU + VA group) during an experimental period of 4 weeks. Results obtained indicate that the iodine uptake and organification, namely iodination of tyrosine residue in thyroglobulin, of the thyroid, were significantly decreased in the DHPN/TU group compared to the DHPN control group. The variation in these values was attributable to the inhibitory effect of TU upon thyroid hormone synthesis. Results obtained from the DHPN/TU + VA and DHPN/TU groups were comparable. Therefore, the possibility that modification of hormone synthesis contributes to the enhancing effect of simultaneous treatment with a large amount of VA on thyroidal tumor induction by TU is considered to be very minimal.

Several 3-substituted 5-chloro-2-methoxybenzamides were synthesized and evaluated for serotonin-3 (5-HT3) receptor binding affinity. The 5-HT3 receptor antagonistic activity of zacopride, a representative 5-HT3 receptor antagonist, was unchanged by the replacement of the 4-amino substituent on the aromatic moiety by a 3-dimethyl-amino substituent. This finding prompted a structural modification of azasetron, another 5-HT3 receptor antagonist. Consequently, a new series of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamides was obtained and these compounds were found to be more potent than 3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-carboxamides. In particular, (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-3,4-dihydro-4-methyl-2H-1,4 -benzoxazine-8-carboxamide showed a high affinity for 5-HT3 receptors K(i) = 0.051 nM) and especially potent antagonistic activity against the von Bezold-Jarisch reflex (ED50 = 0.089 micrograms/kg i.v.) in rats.

A series of N-(azabicyclo-3-yl)-2,3-dihydrobenzofuran-7-carboxamide derivatives were synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activities assessed by 5-HT3 receptor binding (in vitro) and by the ability to antagonize the von Bezold-Jarisch reflex in rats (in vivo). In these compounds, 1-azabicyclo[2.2.2]oct-3-yl derivatives were more potent than 8-methyl-8-azabicyclo[3.2.1]oct-3-yl derivatives for 5-HT3 receptor antagonistic activities. The introduction of methyl groups at position 2 of the dihydrobenzofuran ring increased the pharmacological activities (dimethyl > monomethyl > dihydro). Furthermore, the stereoisomers of dimethyl-, monomethyl-, and dihydrobenzofuran derivatives were prepared to evaluate the stereoselectivity of their 5-HT3 receptor binding affinities. Concerning the basic part, the compounds bearing (S)-1-azabicyclo[2.2.2]octan-3-yl moiety were more potent than their counterparts. With respect to the methyl substituent at position 2 of the dihydrobenzofuran ring, the rank order of the potency was dimethyl > or = (2S)-methyl > (2R)-methyl > dihydro. These results suggest that the (2S)-methyl group of the dihydrobenzofuran part contributes to the enhancement of the pharmacological activity. Among these compounds, (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chloro-2,3-dihydro-2,2- dimethylbenzofuran-7-carboxamide hydrochloride (24) showed the highest affinity for 5-HT3 receptors (Ki = 0.055 nM), and the most potent antagonistic activity on the von Bezold-Jarisch reflex (ED50 = 0.18 microgram/kg i.v.).

The binding of Y-25130 on serotonin 3 (5-HT3) receptors was evaluated by examining its effect on 3H-BRL 43694 (3H-granisetron) binding to rat cerebral cortex membranes in comparison with those of granisetron, ondansetron and metoclopramide. Y-25130, granisetron, ondansetron, metoclopramide, 5-HT and 2-methyl-5-HT displaced the specific binding of 3H-granisetron to the synaptosomal membranes in a concentration-dependent manner. The rank order of potency for inhibition of 3H-granisetron binding by the test compounds was Y-25130 not equal to granisetron greater than ondansetron much greater than 2-methyl-5-HT not equal to 5-HT not equal to metoclopramide. To determine the manner of interaction between Y-25130 and 5-HT3 receptors, Scatchard analysis of 3H-granisetron specific binding to the membranes of the cerebral cortex in the absence or presence of various concentrations of Y-25130 was performed. It was indicated that Y-25130 exerted a typical competitive-type inhibition of 3H-granisetron binding. The present study indicates that Y-25130 binds competitively to 5-HT3 receptors with high affinity.

This paper describes the 5-hydroxytryptamine3 (5-HT3) receptor antagonism of Y-25130 ((+-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4-dih yd ro- 2H-1,4-benzoxazine-8-carboxamide monohydrochloride) in the rat cerebral cortex, isolated rabbit heart and isolated guinea pig ileum. In an in vitro binding assay, Y-25130 inhibited the specific binding of [3H]quipazine to 5-HT3 receptors at the synaptic membranes of the rat cerebral cortex with a Ki value of 2.9 nM, the same as that of ondansetron. Metoclopramide, 5-HT and 2-methyl-5-HT also showed an inhibitory effect, but their affinities for 5-HT3 receptors were lower than that of Y-25130. Y-25130 showed low affinity for histamine H1 receptors (IC50 = 4.4 microM) but it could not reveal any affinities for the other receptors (5-HT1A, 5-HT2, dopamine D1, dopamine D2, alpha 1-adrenoceptor, alpha 2-adrenoceptor, muscarine and benzodiazepine) even at a 10 microM concentration. In the isolated rabbit heart, Y-25130 antagonized the indirect sympathomimetic responses to 5-HT (pA2 value = 10.06) and this effect was more potent than that of metoclopramide. In the isolated longitudinal smooth muscle of the guinea pig ileum, concentration-contraction effect curves for 5-HT were biphasic in the presence of ketanserin. Y-25130 shifted to the right only in the second phase of concentration-effect curves for 5-HT (pA2 value = 7.04) and its activity was more potent than that of metoclopramide. These results indicate that Y-25130 is a potent and selective 5-HT3 receptor antagonist.

The effect of Y-8894 (+/-) 2-[[o-(2-thenyl)phenoxy]methyl] morpholine maleate, which has been shown to improve experimentally induced learning and memory deficits, on cerebral monoamine uptake and turnover was studied in the mouse. The following results were obtained: 1) It inhibited in vitro norepinephrine (NE) uptake to the mouse cerebral synaptosomal fractions about 800 and 1250 times more potently than it did those of dopamine (DA) and serotonin (5-HT), respectively. 2) It dose-dependently inhibited in vivo NE uptake, but not DA or 5-HT uptake. 3) It reduced the accumulation of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), increased that of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and had no effect on that of the DA metabolite, homovanillic acid (HVA). These effects were compared with those of imipramine, calcium hopantenate (Ca-hopantenate) and dihydroergotoxine. Y-8894 appeared to act by stimulating the noradrenergic receptor, and it acts to a lesser extent by blocking the serotonergic receptor in the brain.

The iminodibenzyl antipsychotic drugs, clocapramine, carpipramine and Y-516 were studied in order to elucidate their mechanisms of action. They all accelerated the accumulation of the dopamine (DA) metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), in the striatum and nucleus accumbens of the rat brain. Only Y-516 antagonized in vivo the apomorphine-induced inhibition of DA synthesis as estimated from the accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the decarboxylase-inhibited rat striatum after cessation of nerve impulse flow. All three drugs showed high affinity for DA receptors labelled by [3H]haloperidol and [3H]ADTN in the rat striatum in vitro, with the order of potency Y-516 greater than clocapramine greater than carpipramine. All accelerated the accumulation of the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), in mouse brain. They showed high affinity for alpha 1-adrenoceptors labelled by [3H]WB 4101 and for alpha 2-adrenoceptors labelled by [3H]clonidine in the rat cerebral cortex in vitro. Although they all had the same level of affinity for the alpha 1-adrenoceptors, Y-516 had less affinity for the alpha 2-adrenoceptors than did clocapramine and carpipramine. The above results indicate that these drugs are potent DA antagonists which block alpha 1- and alpha 2-adrenoceptors in the brain.