Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

Allogeneic bone marrow transplantation (alloBMT) is the only curative therapy for chronic myelogenous leukemia (CML). This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI) producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma), and unstimulated (in vivo) lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR), of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2) on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

Päätöksenteon haasteet pelastuslaitosten onnettomuuksien ehkäisyn osastoilla

Työn tavoitteena on selvittää, millaisia haasteita kohdataan pelastuslaitosten onnettomuuksien ehkäisyn osastoilla päätöksiä tehtäessä ja lisäksi selvittää asioita, jotka vaikuttavat päätöksentekoon. Tutkimus suoritettiin kyselytutkimuksena, johon osallistui pelastusviranomaisia ympäri Suomen. Tutkimuksessa kävi ilmi, että lähtökohdat laadukkaalle päätöksenteolle ovat pääsääntöisesti kunnossa. Säädösten osalta pelastuslaissa ja siihen liittyvissä asetuksissa asiat on esitetty paremmin kuin rakentamisen paloturvallisuuteen liittyvissä määräyksissä ja ohjeissa. Jotta päätöksenteko olisi helpompaa ja päätökset yhdenmukaisia valtakunnallisesti, yhteistyöhön ja kumppanuusverkoston toimintaan kannattaa panostaa myös jatkossa.

The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

We compared the clinical efficacy of orally administered valdecoxib and piroxicam for the prevention of pain, trismus and swelling after removal of horizontally and totally intrabony impacted lower third molars. Twenty-five patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Valdecoxib (40 mg) or piroxicam (20 mg) was administered in a double-blind, randomized and crossed manner for 4 days after the surgical procedures. Objective and subjective parameters were recorded for comparison of postoperative courses. Both agents were effective for postoperative pain relief (N = 19). There was a similar mouth opening at suture removal compared with the preoperative values (86.14 ± 4.36 and 93.12 ± 3.70% of the initial measure for valdecoxib and piroxicam, respectively; ANOVA). There was no significant difference regarding the total amount of rescue medication taken by the patients treated with valdecoxib or piroxicam (173.08 ± 91.21 and 461.54 ± 199.85 mg, respectively; Wilcoxon test). There were no significant differences concerning the swelling observed on the second postoperative day compared to baseline measures (6.15 ± 1.84 and 8.46 ± 2.04 mm for valdecoxib and piroxicam, respectively; ANOVA) or on the seventh postoperative day (1.69 ± 1.61 and 2.23 ± 2.09 mm for valdecoxib and piroxicam, respectively; ANOVA). The cyclooxygenase-2 selective inhibitor valdecoxib is as effective as the non-selective cyclooxygenase inhibitor piroxicam for pain, trismus and swelling control after removal of horizontally and totally intrabony impacted lower third molars.

Direct costs of asthma in Brazil: a comparison between controlled and uncontrolled asthmatic patients

Asthma is a common chronic illness that imposes a heavy burden on all aspects of the patient's life, including personal and health care cost expenditures. To analyze the direct cost associated to uncontrolled asthma patients, a cross-sectional study was conducted to determine costs related to patients with uncontrolled and controlled asthma. Uncontrolled patient was defined by daytime symptoms more than twice a week or nocturnal symptoms during two consecutive nights or any limitations of activities, or need for relief rescue medication more than twice a week, and an ACQ score less than 2 points. A questionnaire about direct cost stratification in health services, including emergency room visits, hospitalization, ambulatory visits, and asthma medications prescribed, was applied. Ninety asthma patients were enrolled (45 uncontrolled/45 controlled). Uncontrolled asthmatics accounted for higher health care expenditures than controlled patients, US$125.45 and US$15.58, respectively [emergency room visits (US$39.15 vs US$2.70) and hospitalization (US$86.30 vs US$12.88)], per patient over 6 months. The costs with medications in the last month for patients with mild, moderate and severe asthma were US$1.60, 9.60, and 25.00 in the uncontrolled patients, respectively, and US$6.50, 19.00 and 49.00 in the controlled patients. In view of the small proportion of uncontrolled subjects receiving regular maintenance medication (22.2%) and their lack of resources, providing free medication for uncontrolled patients might be a cost-effective strategy for the public health system.

Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity

This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage.

Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease

The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl-D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). Initially, 16 mg 6-OHDA (6-OHDA group) or vehicle (artificial cerebrospinal fluid - aCSF; Sham group) was infused into the right MFB of adult male Wistar rats. Fifteen days after surgery, the 6-OHDA and SHAM groups were randomly subdivided and received ipsilateral injection of either 60 mM NMDA or aCSF in the right STN. Additionally, a control group was not submitted to stereotaxic surgery. Five groups of rats were studied: 6-OHDA/NMDA, 6-OHDA/Sham, Sham/NMDA, Sham/Sham, and Control. Fourteen days after injection of 6-OHDA, rats were submitted to the rotational test induced by apomorphine (0.1 mg/kg, ip) and to the open-field test. The same tests were performed again 14 days after NMDA-induced lesion of the STN. The STN lesion reduced the contralateral turns induced by apomorphine and blocked the progression of motor impairment in the open-field test in 6-OHDA-treated rats. However, lesion of the STN did not prevent the reduction of striatal concentrations of dopamine and metabolites or the number of nigrostriatal dopaminergic neurons after 6-OHDA lesion. Therefore, STN lesion is able to reverse motor deficits after severe 6-OHDA-induced lesion of the nigrostriatal pathway, but does not protect or rescue dopaminergic neurons in the substantia nigra pars compacta.

The miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation of mouse embryonic cardiomyocytes

MicroRNAs (miRNAs) have gradually been recognized as regulators of embryonic development; however, relatively few miRNAs have been identified that regulate cardiac development. A series of recent papers have established an essential role for the miRNA-17-92 (miR-17-92) cluster of miRNAs in the development of the heart. Previous research has shown that the Friend of Gata-2 (FOG-2) is critical for cardiac development. To investigate the possibility that the miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation in mouse embryonic cardiomyocytes we initially used bioinformatics to analyze 3’ untranslated regions (3’UTR) of FOG-2 to predict the potential of miR-17-92 to target it. We used luciferase assays to demonstrate that miR-17-5p and miR-20a of miR-17-92 interact with the predicted target sites in the 3’UTR of FOG-2. Furthermore, RT-PCR and Western blot were used to demonstrate the post-transcriptional regulation of FOG-2 by miR-17-92 in embryonic cardiomyocytes from E12.5-day pregnant C57BL/6J mice. Finally, EdU cell assays together with the FOG-2 rescue strategy were employed to evaluate the effect of proliferation on embryonic cardiomyocytes. We first found that the miR-17-5p and miR-20a of miR-17-92 directly target the 3’UTR of FOG-2 and post-transcriptionally repress the expression of FOG-2. Moreover, our findings demonstrated that over-expression of miR-17-92 may inhibit cell proliferation via post-transcriptional repression of FOG-2 in embryonic cardiomyocytes. These results indicate that the miR-17-92 cluster regulates the expression of FOG-2 protein and suggest that the miR-17-92 cluster might play an important role in heart development.

Chemical evaluation and effect of bagging new peach varieties introduced in southern Minas Gerais - Brazil

Brazilian peach production is insufficient for domestic supply. Aiming to increase production in the state of Minas Gerais, 16 new peach tree varieties were introduced in the Serra da Mantiqueira region and their fruit were analyzed for sugar, total phenol and total carotenoid contents by colorimetric methods, and for organic acid content by high-performance liquid chromatography. In addition, we examined the effect of fruit bagging on the levels of such constituents. To do so, the fruit of half the trees of each variety were bagged. The levels of sugars, phenols, carotenoids and organic acids are genotypic characteristics and significantly differed among varieties. Despite being a good form of fruit protection, providing better aspect and reducing the need for pesticides, bagging leads to lower contents of components such as sugars, phenols and organic acids in most varieties. However, it cannot be stated that this practice interferes with sensory characteristics. Knowledge of the chemical constituents of these new varieties allows determining those ideal for fresh consumption (e.g., "Maciel", "Diamante", "T. Beauty", "Ouromel 2" and "C.1056", among others) and those more suitable for industrial processing (e.g., "A. Gold", "C.1122" and "C.1050"), as well as those which serve both purposes.

Respostas a uma crítica marxista às perspectivas retórica e pragmática em economia

Answers to a marxist critic of the rhetorical and pragmatic perspectives in economics. Based on recent discussions regarding the rhetorical perspective in economics, this paper presents an interpretation of the philosophical approach of Habermas which attempts to rescue the so called 'modern spirit', forgotten in the annals of the 19th century, similar to that presented by Marshall Berman in 1982. Following the reconstructive approach of Habermas's project of modernity, we attempt to show how a 'rhetorical approach' could be applied in the field of economics, and yet still be clearly modern by taking into account intersubjectivities, given the expanded sphere of human communication (as defended in the theory of communicative action of Habermas). In this sense, we will seek to demonstrate the philosophical limits of the anti-rhetorical critiques of, for example, Paulani (1996, 2003, 2005, 2006), which seem to underestimate the linguistic and intersubjective aspect of Habermas's philosophical project that can also be found in McCloskey’s methodological approach.

Weber e Schumpeter: a ação econômica do empreendedor

Weber and Schumpeter: the Economic action of the entrepreneur. Is there any specificity to be raised in the relations established between entrepreneurs and institutions? Recently, the term entrepreneurship is being widely employed. Enterprising is not anymore a restricted activity to the private sector, but also the Third Sector and the Public Administration. It does not only circumscribe the space of innovation, but also of the adapting changes. In this sense, such elastic concept runs the risk to lose consistency. It seems to be appropriate, therefore, to rescue the meaning that many authors, considered classic in Social Sciences, had attributed to the subject, to show that, although deep socioeconomic transformations occurred since Schumpeter wrote the Theory of the Economic Development, is still necessary to emphasize a basic dimension of the enterprising action: resistance and institutional conflict.

Development and Effect Analysis of the Asteri Consultative Auditing Process - Safety and Security Management in Educational Institutions

The Finnish legislation requires for a safe and secure learning environment. However, the comprehensive, risk based safety and security management (SSM) and the management commitment in the implementation and development of the SSM are not mentioned in the legislation. Multiple institutions, operators and researchers have studied and developed safety and security in educational institutions over the past decade. Typically the approach has been fragmented and without bringing up the importance of the comprehensive SSM. The development needs of the safety and security operations in universities have been studied. However, in universities of applied sciences (UASs) and in elementary schools (ESs), the performance level, strengths and weaknesses of the comprehensive SSM have not been studied. The objective of this study was to develop the comprehensive, risk based SSM of educational institutions by developing the new Asteri consultative auditing process and study its effects on auditees. Furthermore, the performance level in the comprehensive SSM in UASs and ESs were studied using Asteri and the TUTOR model developed by the Keski-Uusimaa Department for Rescue Services. In addition, strengths, development needs and differences were identified. In total, 76 educational institutions were audited between the years 2011 and 2014. The study is based on logical empiricism, and an observational applied research design was used. Auditing, observation and an electronic survey were used for data collection. Statistical analysis was used to analyze the collected information. In addition, thematic analysis was used to analyze the development areas of the organizations mentioned by the respondents in the survey. As one of the main contributions, this research presents the new Asteri consultative auditing process. Organizations with low performance levels on the audited subject benefit the most from the Asteri consultative auditing process. Asteri may be usable in many different types of audits, not only in SSM audits. As a new result, this study provides new knowledge on attitudes related to auditing. According to the research findings, auditing may generate negative attitudes and the auditor should take them into account when planning and preparing for audits. Negative attitudes can be compensated by producing added value, objectivity and positivity for the audit and, thus, improve the positive effects of auditing on knowledge and skills. Moreover, as the results of this study shows, auditing safety and security issues do not increase feelings of insecurity, but rather increase feelings of safety and security when using the new Asteri consultative auditing process with the TUTOR model. The results showed that the SSM in the audited UASs was statistically significantly more advanced than that in the audited ESs. However, there is still room for improvement in the ESs and the UASs as the approach to the SSM was fragmented. It can be assumed that the majority of Finnish UASs and ESs do not likely meet the basic level of the comprehensive, risk based the SSM.

Valtion ohjauksen kehittyminen - case pelastustoimi

Tämän työn tavoitteena on vastata pääkysymykseen, miten sisäministeriö ohjaa pelastustoimen toimialaa ja miten sitä voidaan uudessa järjestelmässä kehittää. Työ on kuvaileva analyysi siitä, miten pelastustoimen toimialaohjausta on toteutettu 1970-luvun puolivälistä nykypäivään. Tavoitteena on kuvata valtion ohjauskeinovalikoimaa ja sitä, miten ohjauskeinoja on pelastustoimessa sovellettu. Keskeinen tavoite on ymmärtää, miten ohjausta on tehty aiemmin ja miten ohjausta tulee tehdä jatkossa, jotta toimialan kehittämistä voidaan tehdä nykyistä paremmin. Työn keskeinen tulos on se, että normi- ja resurssiohjauksen tulee olla keskenään tasapainossa, jota tuetaan tilanteeseen sopivalla informaatio-ohjauksella. Informaatio-ohjauksen tulee perustua vuorovaikutteiseen verkostomaiseen toimintamalliin, jossa toimialan linjauksille haetaan yhteinen sitoutuminen. Tämä edellyttää sisäministeriön ohjausmenetelmien muuttamista perinteisestä normiohjauksesta verkostojen informaatio-ohjaukseksi.

Le Petit journal. Supplément du dimanche

1912/05/19 (Numéro 1122).

Table perpétuelle des textes législatifs... Publication trimestrielle de mise au courant...

1937/07 (N3).