858 resultados para Dose-Response Relationship, Drug.
Resumo:
Minidosimeters of L-alanine and 2-methylalanine (2MA) were prepared and tested as potential candidates for small radiation field dosimetry. To quantify the free radicals created by radiation a K-Band (24 GHz) EPR spectrometer was used. X-rays provided by a 6 MV clinical linear accelerator were used to irradiate the minidosimeters in the dose range of 0.5-30 Gy. The dose-response curves for both radiation sensitive materials displayed a good linear behavior in the dose range indicated with 2MA being more radiation sensitive than L-alanine. Moreover, 2MA showed a smaller LLD (lower limit detection) value. The proposed system minidosimeter/K-Band spectrometer was able to detect 10 Gy EPR spectra with good signal-to-noise ratio (S/N). The overall uncertainty indicates that this system shows a good performance for the detection of dose values of 20 Gy and above, which are dose values typically used in radiosurgery treatments. (c) 2007 Elsevier B.V. All rights reserved.
Resumo:
Acute and chronic nephrotoxicity caused by CsA Continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation.FTY720 is a new Compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens.In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney.Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose Could prevent graft rejection and avoid nephrotoxicity. (c) 2006 Elsevier B.V. All rights reserved.
Resumo:
This study evaluates laboratory microtomography and microhardness analysis for quantifying the mineral content of bovine enamel. Fifty enamel blocks were submitted individually for 5 days to a pH-cycling model at 37 degrees C and remained in the remineralizing solution for 2 days. The blocks were treated twice daily for 1 min with NaF dentifrices (Placebo, 275, 550, 1,100 mu g F/g and Crest (R)) diluted in deionized water. Surface microhardness changes (%SMH) and mineral loss (Delta Z) were then calculated. Laboratory microtomography was also used to measure total mineral lost (LMM). Pearson's correlation (p < 0.05) was used to determine the relationship between different methods of analysis and dose-response between treatments. Dentifrice fluoride concentration and %SMH and Delta Z were correlated (p < 0.05). There was a positive relationship (p < 0.05) when comparing LMM vs. Delta Z; a negative relationship (p < 0.05) was found for %SMH vs. LMM and %SMH vs. Delta Z. Therefore, both mineral quantification techniques provide adequate precision for studying the bovine enamel-pH-cycling demineralization/remineralization model.
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Synchrotron microtomography is a tool to quantify the mineralization of dental tissues as well as microhardness analysis, since they provide adequate precision and contrast sensitivity. This study evaluates synchrotron microtomography and microhardness analysis for quantifying the mineral content of bovine enamel. Fifty enamel blocks were submitted individually for 5 days to a pH-cycling model at 37 degrees C and remained in the remineralizing solution for 2 days. The blocks were treated twice daily for 1 min with NaF dentifrices (Placebo, 275, 550, 1,100 mu g F/g and Crest (R)) diluted in deionized water. Surface microhardness changes (%SMH) and mineral loss (Delta Z) were then calculated. Synchrotron microtomography was also used to measure total mineral lost (SMM). Pearson's correlation (p < 0.05) was used to determine the relationship between different methods of analysis and dose-response between treatments. Dentifrice fluoride concentration and %SMH and Delta Z were correlated (p < 0.05). There was a positive relationship (p < 0.05) when comparing SMM vs. Delta Z; a negative relationship (p < 0.05) was found for %SMH vs. SMM and %SMH vs. Delta Z. Based on the results of this study, it was possible to conclude that synchrotron microtomography provides the best spatial resolution and contrast sensitivity for quantifying mineral gradients.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O papel dos rins no equilíbrio ácido-básico em cães submetidos aos efeitos do halotano e hipercapnia
Resumo:
In eighteen dogs, the effects of halothane (0,75% and 1,5%) associated with a normo and hypercapnia (PaCO2 from 30 to 80 mmHg) on acid-base balance were studied. Determinations of creatine clearance, urinary flow, urinary acid excretion, and urinary ammonium excretion were made. Based on the results, it is concluded that halothane associated with hypercapnia decreases the glomerular filtration rate, the urinary flow, the urinary pH and the urinary bicarbonate and sodium excretion, increases the plasmatic bicarbonate concentration, the bicarbonate reabsorbed, the urinary acid excretion and the urinary ammonium excretion, but does not alter the base excess.
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1. Water intake induced by injection of 0.2 M-NaCl into the lateral preoptic area was increased by the injection of angiotensin II into the subfornical organ of rats. The injection of hypertonic saline solution into the subfornical organ increased water intake. However, the increase was lower than when the solution was injected into the lateral preoptic area. The injection of 4 μg angiotensin II into the lateral preoptic area further augmented this effect. 2. Injection of angiotensin II into the subfornical organ caused a rise in blood pressure which preceded the thirst-inducing effect. The injection of 0.2 M NaCl into the subfornical organ caused no changes in blood pressure, whereas the injection of angiotensin II into the lateral preoptic area caused some increase. 3. Dehydration of the lateral preoptic area by means of 0.2 M NaCl in combination with intravenous infusion of angiotensin II caused a summation of effects in terms of the water intake, without changing cardiovascular alterations induced by the infusion of angiotensin II. A summation of effects in the water intake, but not in blood pressure, was also observed when 0.5 M NaCl was infused intravenously in combination with the injection of angiotensin II into the subfornical organ and into the lateral preoptic area. 4. The results indicate that there are interactions between the subfornical organ and lateral preoptic area in the regulation of cardiovascular and thirst mechanisms.
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The effect of Ketoconazole (KTZ) on the hamster experimental intratesticular paracoccidioidomycosis was studied employing different treatment schedules. KTZ long course treatment beginning at an early stage of the infection was effective in preventing fungal proliferation, dissemination to lymph nodes, spleen and kidneys, and in maintaining low levels of humoral and cellular specific immune responses. KTZ short course treatment starting at an advanced stage of disease resulted in a more severe histopathological picture without significant changes in the immunological profile. The drug prolonged the life span of hamsters infected with Paracoccidioides brasiliensis, but did not prevent mortality. Toxic necrosis of the bone marrow occurred in normal animals receiving 120 mg/kg/day of KTZ but with lower doses no morphologic alterations were observed in heart, lungs, kidneys, adrenals, spleen, liver, intestine or bone marrow. © 1984 Dr W. Junk Publishers.
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In this work we have demonstrated the effects of oral administration of Chlorella vulgaris (CV) on Natural Killer cells (NK) activity of mice infected with a sublethal dose of viable Listeria monocytogenes. The treatment with C. vulgaris produced a significant increase on NK cells activity in normal (non-infected) animals compared to the animals that received only vehicle (water) (p < 0.0001). Similarly, the infection alone produced a significant increase on NK cells activity, which was observed at 48 and 72 hours after the inoculation of L. monocytogenes. Moreover, when CV was administered in infected animals, there was an additional increase in NK cells activity which was significantly higher than that found in the infected groups (p < 0.0001) CV treatment (50 and 500mg/Kg) of mice infected with a dose of 3x105 bacteria/animal, which was lethal for all the non- treated controls, produced a dose-response protection which led to a 20% and 55% survival, respectively (p < 0.0001).
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Background and Objectives - Sevoflurane is an inhalational anesthetic drug with low blood/gas solubility providing fast anesthesia induction and emergence. Its ability to maintain cardiovascular stability makes it ideal for pediatric anesthesia. The aim of this study was to evaluate hemodynamic stability, consumption of inhalational anesthetics and emergence time in children with and without premedication (midazolam or clonidine) anesthetized with sevoflurane titrated according to BIS monitoring. Methods - Participated in this study 30 patients aged 2 to 12 years, physical status ASA I, undergoing elective surgeries who were divided into 3 groups: G1 - without premedication, G2 - 0.5 mg.kg-1 oral midazolam, G3 - 4 μg.kg-1 oral clonidine 60 minutes before surgery. All patients received 30 μg.kg-1 alfentanil, 3 mg.kg-1 propofol, 0.5 mg.kg-1 atracurium, sevoflurane in different concentrations monitored by BIS (values close to 60) and N2O in a non rebreathing system. Systolic and diastolic blood pressure, heart rate, expired sevoflurane concentration (EC), sevoflurane consumption (ml.min-1) and emergence time were evaluated. Emergence time was defined as time elapsed between the end of anesthesia and patients' spontaneous movements trying to extubate themselves, crying and opening eyes and mouth. Results - There were no differences among groups as to systolic and diastolic blood pressure, EC, sevoflurane consumption and emergence time. Heart rate was lower in G3 group. Conclusions - Sevoflurane has provided hemodynamic stability. Premedication with clonidine and midazolam did not influence emergence time, inhaled anesthetic consumption or maintenance of anesthesia with sevoflurane. Anesthesia duration has also not influenced emergence time. Hypnosis monitoring was important for balancing anesthetic levels and this might have been responsible for the similarity of emergence times for all studied groups.
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Background and Objectives - Successful cadaver kidney transplantation relies on a fast procedure. Patients with chronic renal failure may present with a delayed gastric emptying making it critical a fast tracheal intubation and airway maintenance. Rocuronium a recently introduced nondepolarizing neuromuscular blocker with a fast onset. The aim of this study was to evaluate onset time and duration of rocuronium effects in patients undergoing renal transplantation. Methods - Sixty patients were allocated into two groups of 30: Group R (GR) = patients undergoing renal transplantation and Group N (GN) = patients with normal renal function. All patients were premedicated with oral midazolam (15 mg) and anesthesia was induced with 30 μg.kg-1 alfentanil, 0.3 mg.kg-1 etomidate and 0.6 mg.kg-1 rocuronium injected through a central venous catheter. neuromuscular block was monitored by acceleromyography in the ulnar nerve pathway. The following parameters were evaluated: time between administration of rocuronium and first twitch reduction to 5% after supra-maximal stimulation (T1) (onset time = OT); time for first twitch to return to 25% (clinical duration = R25); time elapsed between 25% and 75% recovery of first twitch (relaxation recovery time = R25-75). Heart rate (HR) and mean blood pressure (MBP) were recorded in 6 moments. Results - Median OT was 31 sec. in GR and 47 sec. in GN. Median R25 was 51.5 min in GR and 33.5 min in GN. Median R25-75 was 28 min in GR and 20 min in GN. MBP and HR were higher in GR. Tracheal intubation conditions were excellent for most patients in both groups. Conclusions - These results open the possibility of 0.6 mg.kg-1 rocuronium being injected through a central venous catheter when a faster onset is needed. Due to wide differences in individual responses, monitoring of neuromuscular block is recommended.
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The Cuphea mesostemon specie, known as sete-sangrias, is widely used as a diuretic substance in popular medicine. As the toad urinary bladder is an epithelium analogous to the distal nephron of mammals, it is used in order to study the transport water and electrolytes in many laboratories. This preparation permits excellent observation in water flow, from the urinary bladder lumen to the external side or the serosal one (water re-absorption), by means of gravimetrical measures. In the present work the hydrosmotic effect of aqueous extract (AE) of sete-sangrias leaf was studied. A 20% solution was added to the serosal side (S) of the bladder preparation, and the water flow was measured every 15 minutes after that. The results showed that 4mL of AE in the S side, increased the JH20 in a significant manner (p<0,05). This effect had a dose - response shape, with the volumes of 0,2mL, 0,4mL and 0,8mL of AE in the S bath. The hydro-osmotic effect of the anti-diuretic hormone (ADH) was studied as well and a significant stimulation (p<0,05) in the JH2O was observed with the magnitude of 150%. The AE effect was similar to the ADH one, and was not antagonized by this hormone. We concluded that Cuphea possesses an anti-diuretic activity similar to that presented by ADH, in toad urinary bladder, in vitro.
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The NMDA receptor (NMDAR) channel has been proposed to function as a coincidence-detection mechanism for afferent and reentrant signals, supporting conscious perception, learning, and memory formation. In this paper we discuss the genesis of distorted perceptual states induced by subanesthetic doses of ketamine, a well-known NMDA antagonist. NMDAR blockage has been suggested to perturb perceptual processing in sensory cortex, and also to decrease GABAergic inhibition in limbic areas (leading to an increase in dopamine excitability). We propose that perceptual distortions and hallucinations induced by ketamine blocking of NMDARs are generated by alternative signaling pathways, which include increase of excitability in frontal areas, and glutamate binding to AMPA in sensory cortex prompting Ca++ entry through voltage-dependent calcium channels (VDCCs). This mechanism supports the thesis that glutamate binding to AMPA and NMDARs at sensory cortex mediates most normal perception, while binding to AMPA and activating VDCCs mediates some types of altered perceptual states. We suggest that Ca++ metabolic activity in neurons at associative and sensory cortices is an important factor in the generation of both kinds of perceptual consciousness.