1000 resultados para 24-ethylcoprostanol
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The lipid content of three cores from Lake Enol (Picos de Europa National Park, Asturias, Northern Spain) was studied. The n-alkane profiles indicated a major input from terrigenous plants [predominance of high molecular weight (HMW) alkanes] since ca. 1695 AD to the water body, although the uppermost cm revealed a predominance of organic matter (OM) derived from algae, as the most abundant alkane was C17. Three units revealing different environmental conditions were defined. Unit A (ca. 1695–1860 AD) in the lowermost parts of ENO13-10 (< 12 cm) and ENO13-15 (< 28 cm) was identified and was characterized by higher OM input and evidence of minimal degradation (high CPI values, predominance of HMW n-alkanoic acids and good correspondence between the predominant n-alkane and n-alkanoic acid chains). These findings could be linked to the Little Ice Age, when cold and humid conditions may have favored an increase in total organic carbon (TOC) and n-alkane and n-alkanoic acid content (greater terrigenous OM in-wash), and may have also reduced bacterial activity. In Unit B (ca. 1860–1980 AD) the lack of correspondence between the n-alkane and n-alkanoic acid profiles of ENO13-10 (12–4 cm) and ENO13-15 (28–8 cm) suggested a certain preferential microbial synthesis of long chain saturated fatty acids from primary OM and/or bacterial activity, coinciding with a decrease in OM input, which could be linked to the global warming that started in the second half of the 19th century. In ENO13-7 the low OM input (low TOC) was accompanied by some bacterial degradation (predominance ofHMWn-alkanoic acids but with a bimodal distribution) in the lowermost 16–5 cm. Evidence of considerable phytoplankton productivity and microbial activity was especially significant in Unit C (ca. 1980–2013 AD) identified in the uppermost part of all three cores (5 cm in ENO13-7, 4 cm in ENO13-10 and 8 cm in ENO13-15), coinciding with higher concentrations of n-alkanes and n-alkanoic acids, which were considered to be linked to warmer and drier conditions, as well as to greater anthropogenic influence in modern times. Plant sterols, such as b-sitosterol, campesterol and stigmasterol, were significantly present in the cores. In addition, fecal stanols, such as 24-ethylcoprostanol from herbivores, were present, thereby indicating a continuous and significant pollution input derived from these animals since the 17th century, being more important in the last 20 years.
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Universidade Estadual de Campinas . Faculdade de Educação Física
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Universidade Estadual de Campinas . Faculdade de Educação Física
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PURPOSE: To evaluate the mitochondrial function of the remnant liver (RL) in the early phase of liver regeneration in rats after 70% partial hepatectomy (PH). METHODS: Sixty male Wistar rats (200-250g) submitted to 70% PH were divided into five groups according to the time of euthanasia and application or not of laser light: C = Control, time zero; 2 minutes, 4, 6 and 24 hours after PH. The dose of laser radiation was 22.5 J/cm², wavelength of 660 nm (visible/red), in the remnant liver. We studied the respiration activated by ADP (state 3), basal mitochondrial respiration (state 4), respiratory control ratio (RCR) and mitochondrial membrane potential (MMP). RESULTS: The mitochondrial function of RL changed at 4 and 6 hours after PH, with a significant increase in state 3 and a concomitant increase in state 4 and with maintenance of RCR. MMP differed significantly between the groups biostimulated with laser radiation and the control group 4 hours after HP, with a substantial reduction in the non-laser groups. CONCLUSION: The laser light at the dose used in this study did not induce additional damage to the RL and seems to have delayed the hepatocellular metabolic overload of the remnant liver.
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Atualmente, procuram-se sistemas de manejo que preservem ou melhorem as qualidades do solo, tanto mineralógicas como orgânicas, priorizando maior produtividade. Este trabalho teve como objetivo verificar qualitativamente, por meio das técnicas de fluorescência de raios X, difração de raios X e infravermelho com transformada de Fourier, os efeitos provocados pela utilização dos manejos: plantio convencional, preparo mínimo e plantio direto, por 24 anos, na mineralogia de um Latossolo Vermelho distrófico de Ponta Grossa, PR. Não foram observadas mudanças significativas na mineralogia do Latossolo estudado, por meio das técnicas utilizadas, quanto aos diferentes manejos durante os anos de sua aplicação. Pôde-se verificar, qualitativamente, a presença dos minerais gibbsita, caulinita, haloisita, montmorilonita, hematita, rutilo, anatásio, goethita e quartzo.
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FUNDAMENTO: A recuperação da freqüência cardíaca após o eletrocardiograma de esforço em esteira ergométrica é modulada pelo sistema nervoso autônomo. A análise da variabilidade da freqüência cardíaca (VFC) pode fornecer informações valiosas sobre o controle do sistema nervoso autônomo sobre o sistema cardiovascular. OBJETIVO: O objetivo deste estudo foi testar a hipótese de associação entre a recuperação da freqüência cardíaca após teste de esforço em esteira ergométrica e a variabilidade da freqüência cardíaca. MÉTODOS: Foram estudamos 485 indivíduos sem evidência de cardiopatia com média de idade de 42± 12,1 (faixa etária de 15 a 82) anos, 281 (57.9%) dos quais do sexo feminino, submetidos a um teste de esforço em esteira ergométrica e avaliação da VFC nos domínios do tempo (SDNN, SDANN, SDNNi, rMSSD e pNN50) e da freqüência (LF, HF, VLF e razão LF/HF) durante monitoramento eletrocardiográfico ambulatorial de 24 horas. RESULTADOS: A recuperação da freqüência cardíaca foi de 30 ± 12 batimentos no 1º minuto e 52± 13 batimentos no 2º minuto após o exercício. Os indivíduos mais jovens de recuperaram mais rápido do 2º ao 5º minuto após o exercício (r = 0,19-0,35, P < 0,05). As mulheres se recuperaram mais rápido que os homens (4 ± 1,1 batimentos a menos no 1º minuto, p < 0,001; 5,7 ± 1,2 batimentos a menos no 2º minuto, p < 0,01; e 4,1± 1,1 batimentos a menos no 3º minuto, p < 0.001). Não houve correlação significante entre a recuperação da freqüência cardíaca e a VFC no 1º e 2º minutos após o exercício. Os índices SDNN, SDANN, SDNNi, rMSSD e pNN50 só apresentaram uma correlação significante com a recuperação da freqüência cardíaca no 3º e 4º minutos. CONCLUSÃO: A hipótese de associação entre recuperação da freqüência cardíaca e VFC em 24 horas nos primeiros dois minutos após o exercício não foi comprovada neste estudo. A recuperação da freqüência cardíaca foi associada com idade e sexo.
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Um experimento foi conduzido para verificar o efeito de níveis de fósforo e do tamanho de partícula do fosfato bicálcico na dieta de poedeiras comerciais na fase de produção. Utilizou-se um delineamento experimental inteiramente casualizado, em esquema fatorial 2 × 3 com dois tamanhos de partícula do fosfato (fino e granulado) e três níveis de fósforo disponível (0,28; 0,38 e 0,48%), totalizando seis tratamentos, cada um com cinco repetições de oito aves. As dietas experimentais foram isoproteicas, isocalóricas e isocálcicas. O consumo de ração, a produção de ovos, a massa de ovos, a conversão alimentar, a porcentagem de casca, a gravidade específica e os teores de cinzas, cálcio, fósforo e magnésio nos ossos não foram afetados pelas dietas. Dietas contendo fosfato bicálcico (fino ou granulado) e 0,28% de fósforo disponível atendem às exigências de fósforo de galinhas poedeiras semipesadas de 24 a 58 semanas de idade.
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Context. The space telescope CoRoT searches for transiting extrasolar planets by continuously monitoring the optical flux of thousands of stars in several fields of view. Aims. We report the discovery of CoRoT-10b, a giant planet on a highly eccentric orbit (e = 0.53 +/- 0.04) revolving in 13.24 days around a faint (V = 15.22) metal-rich K1V star. Methods. We used CoRoT photometry, radial velocity observations taken with the HARPS spectrograph, and UVES spectra of the parent star to derive the orbital, stellar, and planetary parameters. Results. We derive a radius of the planet of 0.97 +/- 0.07 R(Jup) and a mass of 2.75 +/- 0.16 M(Jup). The bulk density,rho(p) = 3.70 +/- 0.83 g cm(-3), is similar to 2.8 that of Jupiter. The core of CoRoT-10b could contain up to 240 M(circle plus) of heavy elements. Moving along its eccentric orbit, the planet experiences a 10.6-fold variation in insolation. Owing to the long circularisation time, tau(circ) > 7 Gyr, a resonant perturber is not required to excite and maintain the high eccentricity of CoRoT-10b.
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Fifteen strongly oscillating angular distributions of the elastic scattering of (12)C + (24)Mg at energies around the Coulomb barrier (E(c.m). = 10.67-16.00 MeV) are reproduced by adding five Breit-Wigner resonance terms to the l = 2, 4, 6, 7, and 8 elastic S matrix. The nonresonant, background elastic scattering S matrix S(l)(0) is calculated using the Sao Paulo potential. The J = 2, 4, 6, 7, and 8 (h) over bar molecular resonances fit well into a rotational molecular band, together with other higher lying resonances observed in the (16)O + (20)Ne elastic scattering. We propose that the presently observed, largely deformed molecular band corresponds to the hyperdeformed band, which has been found previously in alpha-cluster calculations, as well as in a new Nilsson model calculation. Systematic study of its possible clusterizations predicts the preference of the (12)C + (24)Mg and (16)O + (20)Ne molecular structure, in accordance with our present results.
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Background: Prevalence rates of smoking are rising in developing countries. Previous trials evaluating the efficacy and tolerability of the smoking-cessation medication varenicline have used largely participants of Caucasian origin. Objective: This study was conducted to evaluate the efficacy and tolerability of varenicline in populations of participants from Latin America, Africa, and the Middle East to investigate potential differences in the therapeutic response to varenicline. Methods: This multinational, randomized, double-blind, placebo-controlled trial was conducted at 42 centers in 11 countries (Latin America: Brazil, Colombia, Costa Rica, Mexico, and Venezuela; Africa: Egypt and South Africa; Middle East: Jordan, Lebanon, Saudi Arabia, and the United Arab Emirates). Participants were male and female smokers aged 18 to 75 years who were motivated to stop smoking; smoked >= 10 cigarettes/d, with no cumulative period of abstinence >3 months in the previous year; and who had no serious or unstable disease within the previous 6 months. Subjects were randomized in a 2:1 ratio to receive varenicline 1 mg or placebo, BID for 12 weeks, with a 12-week nontreatment follow-up. Brief smoking-cessation counseling was provided. The main outcome measures were carbon monoxide confirmed continuous abstinence rate (CAR) at weeks 9 to 12 and weeks 9 to 24. Adverse events (AEs) were recorded for tolerability assessment. Results: Overall, 588 subjects (varenicline, 390; placebo, 198) were randomized and treated. The mean (SD) ages of subjects in the varenicline and placebo groups were 43.1 (10.8) and 43.9 (10.8) years, respectively; 57.7% and 65.7% were male; and the mean (SD) weights were 75.0 (16.0) and 76.7 (16.3) kg (range, 40.0-130.0 and 45.6-126.0 kg). CAR at weeks 9 to 12 was significantly higher with varenicline than with placebo (53.59% vs 18.69%; odds ratio [OR] = 5.76; 95% CI, 3.74-8.88; P < 0.0001), and this rate was maintained during weeks 9 to 24 (39.74% vs 13.13%; OR = 4.78; 95% CI, 2.97-7.68; P < 0.0001). Nausea, headache, and insomnia were the most commonly reported AEs with varenicline and were reported numerically more frequently in the varenicline group compared with the placebo group. Serious AEs (SAEs) were reported in 2.8% of varenicline recipients compared with 1.0% in the placebo group, with 6 subjects reporting psychiatric SAEs compared with none in the placebo group. Conclusion: Based on these data, varenicline was apparently efficacious and generally well tolerated as a smoking-cessation aid in smokers from selected sites in Latin America, Africa, and the Middle East. ClinicalTrials. gov identifier: NCT00594204. (Clin Ther. 2011;33:465-477) (C) 2011 Published by Elsevier HS Journals, Inc.
Development and characterization of novel potent and stable inhibitors of endopeptidase EC 3.4.24.15
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Solid-phase synthesis was used to prepare a series of modifications to the selective and potent inhibitor of endopeptidase EC 3.4.24.15 (EP24.15), N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP), which is degraded at the Ala-Tyr bond, thus severely limiting its utility in vivo. Reducing the amide bond between the Ala and Tyr decreased the potency of the inhibitor to 1/1000. However, the replacement of the second alanine residue immediately adjacent to the tyrosine with alpha-aminoisobutyric acid gave a compound (JA-2) that was equipotent with cFP, with a K-i of 23 nM. Like cFP, JA-2 inhibited the closely related endopeptidase EC 3.4.24.16 1/20 to 1/30 as potently as it did EP24.15, and did not inhibit the other thermolysin-like endopeptidases angiotensin-converting enzyme, endothelin-converting enzyme and neutral endopeptidase. The biological stability of JA-2 was investigated by incubation with a number of membrane and soluble sheep tissue extracts. In contrast with cFP, JA-2 remained intact after 48 h of incubation with all tissues examined. Further modifications to the JA-2 compound failed to improve the potency of this inhibitor. Hence JA-2 is a potent, EP24.15-preferential and biologically stable inhibitor, therefore providing a valuable tool for further assessing the biological functions of EP24.15.
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We have developed a novel inhibitor of the metalloendopeptidases EC 3.4.24.15 (EP24.15) and EC 3.4.24.16 (EP24.16), N-[1-(R, S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (JA2), in which alpha-aminoisobutyric acid (Aib) is substituted for an alanine in a well-described but unstable inhibitor, cFP-AAY-pAB. This substitution increases the resistance of the inhibitor to degradation without altering potency. In the present study, we investigated the effects of JA2 (5 mg/kg) on the responses of mean arterial pressure to bradykinin, angiotensin I, and angiotensin II in conscious rabbits. The depressor responses to both low (10 ng/kg) and high (100 ng/kg) doses of bradykinin were increased 7.0 +/- 2.7-fold and 1.5 +/- 0.3-fold, respectively, during the 30 minutes after JA2 administration (mean+/-SEM, n=8). Bradykinin potentiation was undiminished 4 hours after JA2 injection. In contrast, the hypertensive effects of angiotensins I and II were unaltered, indicating that the bradykinin-potentiating effects were not due to angiotensin-converting enzyme inhibition. These data suggest that JA2 is not only a potent and specific inhibitor of EP24.15 and EP24.16 but is also stable in vivo. Furthermore, the potentiation of bradykinin-induced hypotension by JA2 suggests for the first time a role for one or both of these peptidases in the metabolism of bradykinin in the circulation.
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OBJECTIVE: Hypoglossal-facial neurorrhaphy has been widely used for reanimation of paralyzed facial muscles after irreversible proximal injury of the facial nerve. However, complete section of the hypoglossal nerve occasionally results in hemiglossal dysfunction and interferes with swallowing and speech. To reduce this morbidity, a modified technique with partial section of the hypoglossal nerve after mastoid dissection of the facial nerve (HFM) has been used. We report our experience with the HFM technique, retrospectively comparing the outcome with results of the classic hypoglossal-facial neurorrhaphy. METHODS: A retrospective review was performed in 36 patients who underwent hypoglossal-facial neurorrhaphy with the classic (n = 12) or variant technique (n = 24) between 2000 and 2006. Facial Outcome was evaluated with the House-Brackmann grading system, and tongue function was evaluated with a new scale proposed to quantify Postoperative tongue alteration. The results were compared, and age and time between nerve injury and surgery were correlated with the outcome. RESULTS: There was no significant difference between the two techniques concerning facial reanimation. A worse outcome of tongue function, however, was associated with the classic technique (Mann-Whitney U test; P < 0.05). When HFM was used, significant correlations defined by the Spearman test were identified between preoperative delay (p = 0.59; P = 0.002) or age (p = 0.42; P = 0.031) and results of facial reanimation evaluated with the House-Brackmann grading system. CONCLUSION: HFM is as effective as classic hypoglossal-facial neurorrhaphy for facial reanimation, and it has a much lower morbidity related to tongue function. Better results are obtained in younger patients and with a shorter interval between facial nerve injury and surgery.
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Background: Despite antihypertensive therapy, it is difficult to maintain optimal systemic blood pressure (BP) values in hypertensive patients (HPT). Exercise may reduce BP in untreated HPT. However, evidence regarding its effect in long-term antihypertensive therapy is lacking. Our purpose was to evaluate the acute effects of 40-minute continuous (CE) or interval exercise (IE) using cycle ergometers on BP in long-term treated HPT. Methods: Fifty-two treated HPT were randomized to CE (n=26) or IE (n=26) protocols. CE was performed at 60% of reserve heart rate (HR). IE alternated consecutively 2 min at 50% reserve HR with 1 min at 80%. Two 24-h ambulatory BP monitoring were made after exercise (postexercise) or a nonexercise control period (control) in random order. Results: CE reduced mean 24-h systolic (S) BP (2.6 +/- 6.6 mm Hg, p-0.05) and diastolic (D) BP (2.3 +/- 4.6, p-0.01), and nighttime SBP (4.8 +/- 6.4, p < 0.001) and DBP (4.6 +/- 5.2 mm Hg, p-0.001). IE reduced 24-h SBP (2.8 +/- 6.5, p-0.03) and nighttime SBP (3.4 +/- 7.2, p-0.02), and tended to reduce nighttime DBP (p=0.06). Greater reductions occurred in higher BP levels. Percentage of normal ambulatory BP values increased after CE (24-h: 42% to 54%; daytime: 42% to 61%; nighttime: 61% to 69%) and IE (24-h: 31% to 46%; daytime: 54% to 61%; nighttime: 46% to 69%). Conclusion: CE and IE reduced ambulatory BP in treated HPT, increasing the number of patients reaching normal ambulatory BP values. These effects suggest that continuous and interval aerobic exercise may have a role in BP management in treated HPT. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
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Background. Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria. Methods. During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance ((51)Cr-EDTA mL/min/1.73 m(2)) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR >= 90mL/min/1.73 m(2), stage II as 60-89 mL/min/1.73m(2), stage III as 30-59 mL/min/1.73 m(2), stage IV as 15-29 mL/min/1.73m(2), and stage V as < 15 mL/min/1.73m(2). Results. Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 +/- 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions administered. Conclusion. Over the course of 36 months of ERT, there was no change in kidney function and 24-hour proteinuria. This suggests thatagalsidase alfa may slow or halt the progression of kidney disease when used before extensive kidney damage occurs. No significant side effects were observed with ERT during the course of the study.