60 resultados para phase I trials


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Gluconeogenic activity and kinetic parameters of glucose metabolism were estimated during the different phases of prolonged food deprivation in quails. Gluconeogenic activity, estimated from the rate of increase of incorporation of (HCO3-)-C-14 into circulating glucose, was significantly higher in fasted quails than in fed birds, whatever the period of food deprivation. However, gluconeogenic activity during phase II, although higher than in the fed state, was significantly lower than in quails fasted for 2 days (phase I) or in those on the final (phase III) period of starvation. Gluconeogenic activity did not differ significantly in birds from phases I and III. Rates of glucose replacement, estimated with [6-H-3]-glucose, were very high (20.5 mg . kg(-1). min(-1)) in fed quails and were markedly reduced (to about 42% of fed values) by fasting, no difference being observed between quails fasted for 2 and 5 days. Because of the poor condition of the birds, glucose replacement rates could not be measured during phase III. The present data are the first to provide direct evidence for the changes in gluconeogenesis which occur during prolonged food deprivation.

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Water temperature alterations can determine harmful physiological modifications in fish, which should be prepared to cope with this, and nutrition strategies seem to be essential. This study evaluated the effects of different levels of vitamin C and lipids on physiological responses of Nile tilapia, Oreochromis niloticus, submitted to temperature stress. There were two phases: Phase I - preparing fish to store vitamin C and lipid at appropriate temperature, and Phase II - evaluating the contributions these reserves make to fish physiology under low-temperature stress. The experiment used a 3 x 2 factorial design with three vitamin C levels (300, 600, and 1200 mg/kg diet) and two lipid levels (8.0 and 12.0%), plus absence of nutrient test and a diet of 6.0% lipids and 125.0 mg/kg vitamin C. In Phase I, 192 fish were kept at 26.0 +/- 1.0 C for 112 d, and in Phase II, 48 fish were kept at 18.0 +/- 0.5 C for 32 d and at 15.0 +/- 0.5 C for 11 d. Fish fed C0L0 diet showed lower erythrocytes values in both phases; higher vitamin C supplement determined higher red blood cell (RBC) number and higher hematocrit (Htc) (Phase II); Htc was significantly lower in Phase II; after temperature stress, fish fed C0L0 diet had higher mean corpuscular volume, lower hemoglobin corpuscular concentration, and significantly lower vitamin C concentration in the liver; and higher supplementation determined a higher concentration in the liver (Phases I and II). Higher plasmatic cortisol concentration was seen in fish fed C0L0 diet. In conclusion, our results show that the absence of vitamin C in diets impairs RBC formation and does not enable fish to cope with stress; excess vitamin C is efficient in mitigating stress and 600 mg/kg diet is economic and physiologically sufficient to prepare fish for coping with low-temperature stress. Lipid supplementation does not determine alterations in stress biochemical parameters.

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Objective-To evaluate the effects of 2 remifentanil infusion regimens on cardiovascular function and responses to nociceptive stimulation in propofol-anesthetized cats.Animals-8 adult cats.Procedures-On 2 occasions, cats received acepromazine followed by propofol (6 mg/kg then 0.3 mg/kg/min, IV) and a constant rate infusion (CRI) of remifentanil (0.2 or 0.3 mu g/kg/min,IV) for 90 minutes and underwent mechanical ventilation (phase I). After recording physiologic variables, an electrical stimulus (50 V; 50 Hz; 10 milliseconds) was applied to a forelimb to assess motor responses to nociceptive stimulation. After an interval (>= 10 days), the same cats were anesthetized via administration of acepromazine and a similar infusion regimen of propofol; the remifentanil infusion rate adjustments that were required to inhibit cardiovascular responses to ovariohysterectomy were recorded (phase II).Results-In phase I, heart rate and arterial pressure did not differ between remifentanil-treated groups. From 30 to 90 minutes, cats receiving 0.3 mu g of remifentanil/kg/min had no response to noxious stimulation. Purposeful movement was detected more frequently in cats receiving 0.2 mu g of remifentanil/kg/min. In phase II, the highest dosage (mean +/- SEM) of remifentanil that prevented cardiovascular responses was 0.23 +/- 0.01 mu g/kg/min. For all experiments, mean time from infusion cessation until standing ranged from 115 to 140 minutes.Conclusions and Clinical Relevance-Although the lower infusion rate of remifentanil allowed ovariohysterectomy to be performed, a CRI of 0.3 mu g/kg/min was necessary to prevent motor response to electrical stimulation in propofol-anesthetized cats. Recovery from anesthesia was prolonged with this technique.

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A continuous flow reactor, inoculated with Aspergillus niger AN400, with total volume of 5 L was operated at 29 degrees C, with eight hours of retention hydraulic time and 150 L.h(-1) of air flow rate in order to remove 25 mg.L(-1) of Congo Red dye from a synthetic wastewater. The feeding of the reactor, inoculated with Aspergillus niger AN400, was done in two phases: Phase I, with 0,5 g/L of saccharose and Phase II, with no saccharose. In Phase I, it was possible to verify efficiencies of organic matter and color (mg Pt.L(-1)) removal of 80 +/- 16% and 82 +/- 10%, respectively. In Phase II, the efficiency of organic matter removal was 75 +/- 13% and color removal was 89 +/- 7%. The higher removals of nutrients were achieved by the reactor in Phase I with 25% to ammonia, 90% to nitrite, 93% to nitrate and 21% to phosphorus. Apparently, the presence of saccharose improved the removal of the nutrients.

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The VSS X chart, dedicated to the detection of small to moderate mean shifts in the process, has been investigated by several researchers under the assumption of known process parameters. In practice, the process parameters are rarely known and are usually estimated from an in-control Phase I data set. In this paper, we evaluate the (run length) performances of the VSS chart when the process parameters are estimated, we compare them in the case where the process parameters are assumed known and we propose specific optimal control chart parameters taking the number of Phase I samples into account.

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After up to 21 days without food, adult male quails (Coturnix coturnix japonica) lost about 45% of the initial body weight (100-150 g). As in naturally fast-adapted and larger birds, three phases were identified during prolonged fasting in quails. Phase I lasted 2-3 days and was characterized by a rapid decrease in the rate of body weight loss and high fat mobilization. Phase II was longer and characterized by a slow and steady decline in the rates of body weight loss and of nitrogen excretion. The third (critical) period was marked by an abrupt increase in the rates of body weight loss and of nitrogen excretion. Despite their small size, the duration of phase II in quails was relatively long, a clear advantage for the study of the relationships between the several metabolic events that occur during this crucial adaptative period. Also, the beginning of phase III could be precisely determined. Changes in blood glucose, plasma FFA and triacylglycerols levels, as well as in liver and carcass lipid content were similar to those found in other species of birds. Therefore, quails seem to be a suitable model to investigate the biochemical mechanisms involved in the metabolic adjustments to prolonged food deprivation in non fasting-adapted birds. © 1995.

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The objective of this study was to evaluate the effects of the use of recombinant bovine somatotropin (rbST) in weight gain, feeding efficiency and chemical characteristics of meat of young bulls. Fifty nine young bulls were used: 30 crossbred Simmental x Nelore and 29 Nelore aging between seven to eight months, weighing 236 and 116 kg, respectively. A randomized experiment in a 2 × 2 factorial arrangement was used. There were two levels of rbST (0 and 250 mg/animal/14 days) and two breed groups subdivided in two experimental phases. Diet was based on corn silage and concentrate aiming at a weight gain of 0.8 a day for Phase I (70 days) and 1.3 kg for Phase II (98 days). Animals were slaughtered at 13 months of age and the measurements of carcass dressing and meat quality were taken. Results showed that cross-breeding animals overcame (p<.01) the Nelore breed in weight gain and final weight at slaughtering. Use of rbST has not influenced weight gain, final weight, carcass weight and chemical characteristics of meat (p>.05). The use of rbST improved feeding efficiency 11.91 % for cross-bred and 24.32% for Nelore in Phase II.

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The lateral shoots of the Aloe vera L. Burm have been inoculated in culture medium. The work has been divided in two phases. In the phase I different concentrations of NAA and BAP were added to the MS . In the phase II, plants proceeding of the MS were inoculated in medium containing or not spermidine and/or spermine. In the phase I the best results for mass production and shooting came out with the use of MS + 8,88 m mol L -1 BAP + 5,36 m mol L -1 NAA and these treatments didn't induce the rooting. Plants submitted to treatments with polyamines presented emission of roots during the phase II, suggesting possible inductor effect when used by isolated means during the rooting. No traces of oxidation were noted in the culture medium containing the polyamines. The use of spermidine in the culture-medium promoted a greater mass increasing and the most number of shoots was obtained with the use of the combination of polyamines. © 2008 1999, Editorial Ciencias Médicas.

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In Brazil, the registration of new drugs is carried out only when the regulatory agency (Anvisa, acronym in Portuguese) is fully satisfied with the evidence of their quality, efficacy and safety, presented by a pharmaceutical industry that strive for this registration. With the patent expiration, pharmaceutical companies are attracted to produce biological medicines called biosimilar or biogenerics or simply generics, whose approval may result in reduced treatment costs. But it is necessary that the biosimilar be, at least, equally efective and safe and without contaminants in relation to the original. Recent consensus guidelines aim to establish criteria for efcacy and safety of these medicines. Preclinical studies in vitro and in vivo, the origin of raw materials and clinical studies phase I, II and III are recommended for biosimilar medicine registration in the international market. Low molecular weight heparins are found in this situation. In this review we specifcally addressed this type of medicine, which could serve as a benchmark for other biosimilar medicines.

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The VSS X- chart is known to perform better than the traditional X- control chart in detecting small to moderate mean shifts in the process. Many researchers have used this chart in order to detect a process mean shift under the assumption of known parameters. However, in practice, the process parameters are rarely known and are usually estimated from an in-control Phase I data set. In this paper, we evaluate the (run length) performances of the VSS X- control chart when the process parameters are estimated and we compare them in the case where the process parameters are assumed known. We draw the conclusion that these performances are quite different when the shift and the number of samples used during the phase I are small. ©2010 IEEE.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Pós-graduação em Ciência Animal - FMVA