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The efficacy and safety of anti-infective treatments are associated with the drug blood concentration profile, which is directly correlated with a dosing adjustment to the individual patient's condition. Dosing adjustments to the renal function recommended in reference books are often imprecise and infrequently applied in clinical practice. The recent generalisation of the KDOQI (Kidney Disease Outcome Quality Initiative) staging of chronically impaired renal function represents an opportunity to review and refine the dosing recommendations in patients with renal insufficiency. The literature has been reviewed and compared to a predictive model of the fraction of drug cleared by the kidney based on the Dettli's principle. Revised drug dosing recommendations integrating these predictive parameters are proposed.

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Considering macrophage migratory inhibitory factor (MIF) as a critical pro-inflammatory cytokine of the immune system, we evaluated plasma MIF levels in 89 HIV-infected adults. Plasma MIF levels were higher in HIV-infected than in HIV-negative individuals. Highest MIF levels were observed during acute HIV infection (AHI) whilst patients on antiretroviral therapy (ART) had lower MIF levels, regardless of ART efficacy. Our results suggest that MIF is an integral component of the cytokine storm characteristic of AHI.

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The aim of this study was to evaluate abundance, biomass and diversity of earthworms in the southern coast region of the Mata Atlântica biodiversity hotspot. A total of 51 study sites in pastures, banana monocultures, mixed agroforestry systems, secondary forests in succession and old-growth forests near the coast of Paraná, Brazil, were evaluated. Each site was sampled once. Species richness of the earthworms was generally low and varied little between sites. At all sites except for one, the peregrine species Pontoscolex corethrurus (Glossoscolecidae) strongly dominated. Three other peregrine species, Amynthas corticis, Amynthas gracilis (Megascolecidae) and Ocnerodrilus occidentalis (Ocnerodrilidae), were frequent in moist sites. No autochthonous species were found. Abundance and biomass of earthworms varied strongly within and between sites (0-338 individuals m-2, 0-96 g m-2 fresh weight). Pastures had significantly lower abundance than all other sites. The forest sites had similar earthworm abundance and biomass, with a tendency to be higher in younger succession stages. The coastal plain region has been strongly altered by human activities. Reasons for the lack of any autochthonous species and the dominance of one peregrine species require further investigation.

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Tissue protein hypercatabolism (TPH) is a most important feature in cancer cachexia, particularly with regard to the skeletal muscle. The rat ascites hepatoma Yoshida AH-130 is a very suitable model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle waste mainly due to TPH (Tessitore, L., G. Bonelli, and F. M. Baccino. 1987. Biochem. J. 241:153-159). Detectable plasma levels of tumor necrosis factor-alpha associated with marked perturbations in the hormonal homeostasis have been shown to concur in forcing metabolism into a catabolic setting (Tessitore, L., P. Costelli, and F. M. Baccino. 1993. Br. J. Cancer. 67:15-23). The present study was directed to investigate if beta 2-adrenergic agonists, which are known to favor skeletal muscle hypertrophy, could effectively antagonize the enhanced muscle protein breakdown in this cancer cachexia model. One such agent, i.e., clenbuterol, indeed largely prevented skeletal muscle waste in AH-130-bearing rats by restoring protein degradative rates close to control values. This normalization of protein breakdown rates was achieved through a decrease of the hyperactivation of the ATP-ubiquitin-dependent proteolytic pathway, as previously demonstrated in our laboratory (Llovera, M., C. García-Martínez, N. Agell, M. Marzábal, F. J. López-Soriano, and J. M. Argilés. 1994. FEBS (Fed. Eur. Biochem. Soc.) Lett. 338:311-318). By contrast, the drug did not exert any measurable effect on various parenchymal organs, nor did it modify the plasma level of corticosterone and insulin, which were increased and decreased, respectively, in the tumor hosts. The present data give new insights into the mechanisms by which clenbuterol exerts its preventive effect on muscle protein waste and seem to warrant the implementation of experimental protocols involving the use of clenbuterol or alike drugs in the treatment of pathological states involving TPH, particularly in skeletal muscle and heart, such as in the present model of cancer cachexia.

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Tissue protein hypercatabolism (TPH) is a most important feature in cancer cachexia, particularly with regard to the skeletal muscle. The rat ascites hepatoma Yoshida AH-130 is a very suitable model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle waste mainly due to TPH (Tessitore, L., G. Bonelli, and F. M. Baccino. 1987. Biochem. J. 241:153-159). Detectable plasma levels of tumor necrosis factor-alpha associated with marked perturbations in the hormonal homeostasis have been shown to concur in forcing metabolism into a catabolic setting (Tessitore, L., P. Costelli, and F. M. Baccino. 1993. Br. J. Cancer. 67:15-23). The present study was directed to investigate if beta 2-adrenergic agonists, which are known to favor skeletal muscle hypertrophy, could effectively antagonize the enhanced muscle protein breakdown in this cancer cachexia model. One such agent, i.e., clenbuterol, indeed largely prevented skeletal muscle waste in AH-130-bearing rats by restoring protein degradative rates close to control values. This normalization of protein breakdown rates was achieved through a decrease of the hyperactivation of the ATP-ubiquitin-dependent proteolytic pathway, as previously demonstrated in our laboratory (Llovera, M., C. García-Martínez, N. Agell, M. Marzábal, F. J. López-Soriano, and J. M. Argilés. 1994. FEBS (Fed. Eur. Biochem. Soc.) Lett. 338:311-318). By contrast, the drug did not exert any measurable effect on various parenchymal organs, nor did it modify the plasma level of corticosterone and insulin, which were increased and decreased, respectively, in the tumor hosts. The present data give new insights into the mechanisms by which clenbuterol exerts its preventive effect on muscle protein waste and seem to warrant the implementation of experimental protocols involving the use of clenbuterol or alike drugs in the treatment of pathological states involving TPH, particularly in skeletal muscle and heart, such as in the present model of cancer cachexia.

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Tissue protein hypercatabolism (TPH) is a most important feature in cancer cachexia, particularly with regard to the skeletal muscle. The rat ascites hepatoma Yoshida AH-130 is a very suitable model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle waste mainly due to TPH (Tessitore, L., G. Bonelli, and F. M. Baccino. 1987. Biochem. J. 241:153-159). Detectable plasma levels of tumor necrosis factor-alpha associated with marked perturbations in the hormonal homeostasis have been shown to concur in forcing metabolism into a catabolic setting (Tessitore, L., P. Costelli, and F. M. Baccino. 1993. Br. J. Cancer. 67:15-23). The present study was directed to investigate if beta 2-adrenergic agonists, which are known to favor skeletal muscle hypertrophy, could effectively antagonize the enhanced muscle protein breakdown in this cancer cachexia model. One such agent, i.e., clenbuterol, indeed largely prevented skeletal muscle waste in AH-130-bearing rats by restoring protein degradative rates close to control values. This normalization of protein breakdown rates was achieved through a decrease of the hyperactivation of the ATP-ubiquitin-dependent proteolytic pathway, as previously demonstrated in our laboratory (Llovera, M., C. García-Martínez, N. Agell, M. Marzábal, F. J. López-Soriano, and J. M. Argilés. 1994. FEBS (Fed. Eur. Biochem. Soc.) Lett. 338:311-318). By contrast, the drug did not exert any measurable effect on various parenchymal organs, nor did it modify the plasma level of corticosterone and insulin, which were increased and decreased, respectively, in the tumor hosts. The present data give new insights into the mechanisms by which clenbuterol exerts its preventive effect on muscle protein waste and seem to warrant the implementation of experimental protocols involving the use of clenbuterol or alike drugs in the treatment of pathological states involving TPH, particularly in skeletal muscle and heart, such as in the present model of cancer cachexia.

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The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension.The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated.The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics.Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present.In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference.

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A cross-over controlled administration study of smoked cannabis was carried out on occasional and heavy smokers. The participants smoked a joint (11 % Δ9-tetrahydrocannabinol (THC)) or a matching placebo on two different occasions. Whole blood (WB) and oral fluid (OF) samples were collected before and up to 3.5 h after smoking the joints. Pharmacokinetic analyses were obtained from these data. Questionnaires assessing the subjective effects were administered to the subjects during each session before and after the smoking time period. THC, 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) were analyzed in the blood by gas chromatography or liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The determination of THC, THCCOOH, cannabinol (CBN), and Δ9-tetrahydrocannabinolic acid A (THC-A) was carried out on OF only using LC-MS/MS. In line with the widely accepted assumption that cannabis smoking results in a strong contamination of the oral cavity, we found that THC, and also THC-A, shows a sharp, high concentration peak just after smoking, with a rapid decrease in these levels within 3 h. No obvious differences were found between both groups concerning THC median maximum concentrations measured either in blood or in OF; these levels were equal to 1,338 and 1,041 μg/L in OF and to 82 and 94 μg/L in WB for occasional and heavy smokers, respectively. The initial WB THCCOOH concentration was much higher in regular smokers than in occasional users. Compared with the occasional smokers, the sensation of confusion felt by the regular smokers was much less while the feeling of intoxication remained almost unchanged.

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O objetivo deste trabalho foi avaliar o efeito da adubação com N e K sobre a produtividade e a bienalidade de produção de cafeeiros em plantio adensado, em estudo de longa duração. Foram avaliados dois experimentos, na região da Zona da Mata de Minas Gerais, conduzidos em blocos ao acaso, com parcelas subdivididas no tempo. No primeiro experimento, realizado no espaçamento de 1,5x0,7 m (9.523 plantas por hectare), foram avaliados os efeitos de sete doses de N + K2O na proporção 1:1 (0, 200, 400, 600, 800, 1.000 e 1.200 kg ha‑1 por ano), durante oito safras (2001/2002 a 2008/2009). Como o fertilizante utilizado tinha proporção 1:1, para obter a dose utilizada de cada elemento (N ou K2O), deve-se dividir a dose total por dois. O segundo experimento foi conduzido no espaçamento de 2,5x0,6 m (6.666 plantas por hectare), em arranjo fatorial, com cinco doses de N (0, 150, 300, 450 e 600 kg ha‑1 por ano) e cinco doses de K2O (0, 150, 300, 450 e 600 kg ha‑1 por ano), durante seis safras (2005/2006 a 2010/2011). As doses associadas à máxima produtividade de café beneficiado variaram de 424 a 560 kg ha‑1, para N, e de 21 a 338 kg ha‑1, para K2O. A adubação com N reduz os efeitos da bienalidade da produção do cafeeiro, e a adubação com K, em anos de baixa produtividade, favorece a recuperação da produtividade do cafeeiro no ano seguinte.

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O objetivo deste trabalho foi descrever a morfologia das gônadas do surubim-do-paraíba (F1) durante a reprodução induzida em cativeiro. Trinta fêmeas foram induzidas, tendo-se utilizado extrato hipofisário de carpa e gonadotrofina coriônica humana. Vinte e oito fêmeas responderam à indução, tendo liberado 238,80 g de ovócitos (taxa de fertilização: 24,33±8,35%). Após a extrusão dos gametas, os animais foram eutanasiados para análise morfológica das gônadas. Os testículos não apresentaram alterações morfológicas após a indução. Entre os ovários, 63,31% apresentaram má formação (desenvolvimento ímpar, não uniforme ou "afunilamento"), e o número de ovócitos liberados foi abaixo do obtido em reprodutores selvagens desta espécie.

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ESIPUHE Julkaisun artikkelit liittyvät ajankohtaiseen teemaan: demokratian ja osallistumisen tulevaisuuden kehitys. Suomalainen hyvinvointivaltio julkisen sektorin tuottamine palveluineen tarvitsee tuekseen kansalaisten sitoutumisen yhteisen hyvän puolesta. Järjestelmän edellytyksenä on demokraattisen päätöksenteon rakenteiden ja käytännön toteuttamisen kehittäminen niin, että tällä hetkellä vielä koulussa olevat nuoret saadaan kiinnostumaan entistä voimakkaammin yhteisten asioiden hoitamisesta. Artikkelikokoelmamme liittyy saumattomasti parhaillaan meneillään olevaan tutkimus- ja kehittämishankkeeseen, jossa luomme sekä sisältöjä että teknologiaa tukemaan nuorten kunnallista e-demokratiaa. Ampers -hanke (Ambient Personalised Society) eli nuoret ja mediayhteisöllisyys on ainutlaatuinen kombinaatio taiteiden, yhteiskuntatieteiden jateknologian tutkimusta. Osallistujina hankkeessamme ovat erityisesti nuoret. Käsittelemme kirjoituksissamme informaatioyhteiskunnan, virtuaaliorganisaatioiden ja tulevaisuuden osallistumisen visioita. Outi Cavén aloittaa kokoelman koko julkaisua taustoittavalla artikkelillaan. Kari Heikkinen jatkaa edellä mainittua teemaa pohtiessaan teknologian mahdollisuuksia tukea demokratian toteuttamisen arkea. Miia Kosonen on analysoinut sekä kaikenikäisille että erityisesti nuorille suunnattuja suomalaisia osallistumisen ja e-demokratian harjoittamisen sivustoja.Pelin henki -artikkelissa Cavén luo katseen virtuaalisen maailman pelisääntöihin ja uhkiin. Päätämme artikkelikokoelman menetelmälliseen katsaukseen, jossa Hanna-Kaisa Ellonen ja Outi Cavén esittelevät ryhmähaastattelun perusteita. Artikkelikokoelma on ensimmäinen hankkeemme yhteisjulkaisu. Toivomme lukijoille mielenkiintoisia hetkiä ajatustemme ja tutkimuksen lähtökohtiemme tarkastelujen parissa

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The complexity of the connexions within an economic system can only be reliably reflected in academic research if powerful methods are used. Researchers have used Structural Path Analysis (SPA) to capture not only the linkages within the production system but also the propagation of the effects into different channels of impacts. However, the SPA literature has restricted itself to showing the relations among sectors of production, while the connections between these sectors and final consumption have attracted little attention. In order to consider the complete set of channels involved, in this paper we propose a structural path method that endogenously incorporates not only sectors of production but also the final consumption of the economy. The empirical application comprises water usages, and analyses the dissemination of exogenous impacts into various channels of water consumption. The results show that the responsibility for water stress is imputed to different sectors and depends on the hypothesis used for the role played by final consumption in the model. This highlights the importance of consumers’ decisions in the determination of ecological impacts. Keywords: Input-Output Analysis, Structural Path Analysis, Final Consumption, Water uses.