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Intermediate Doses (intermediate + dose)
Selected AbstractsBicuculline-induced brain activation in mice detected by functional magnetic resonance imagingMAGNETIC RESONANCE IN MEDICINE, Issue 2 2001Thomas Mueggler Abstract Dynamic measurements of local changes in relative cerebral blood volume (CBVrel) during a pharmacological stimulation paradigm were performed in mice. Using magnetite nanoparticles as an intravascular contrast agent, high-resolution CBVrel maps were obtained. Intravenous administration of the GABAA antagonist bicuculline prompted increases in local CBVrel as assessed by MRI with a high spatial resolution of 0.2 × 0.2 mm2 and a temporal resolution of 21 s. Signal changes occurred 20,30 s after the onset of drug infusion in the somatosensory and motor cortex, followed by other cortical and subcortical structures. The magnitudes of the CBVrel increases were 18% ± 4%, 46% ± 14%, and 67% ± 7%, as compared to prestimulation values for the cortex, and 9% ± 3%, 25% ± 4%, and 36% ± 7% for the caudate putamen for bicuculline doses of 0.6, 1.25, and 1.5 mg/kg, respectively. On-line monitoring of transcutaneous carbon dioxide tension PtcCO2 reflecting arterial PaCO2 did not show any alteration during the stimulation paradigm. One of five of the mice receiving the highest bicuculline dose, and three of seven receiving the intermediate dose displayed a different cortical response pattern. After a CBVrel increase of 40% lasting for approximately 1 min, significant CBVrelreductions by 80% have been observed. Subcortical structures did not display this behavior. The present study suggests that this noninvasive approach of functional MRI (fMRI) can be applied to study drug-induced brain activation by central nervous system (CNS) drugs in mice under normal and pathological situations. Magn Reson Med 46:292,298, 2001. © 2001 Wiley-Liss, Inc. [source] Intensive induction chemotherapy with regimen containing intermediate dose cytarabine in the treatment of de novo acute myeloid leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2009Jiazhuo Liu To improve long-term outcome of de novo acute myeloid leukemia (AML) patients by intermediate dose of cytarabine integrated in induction therapy and to explore the impact of cytogenetic abnormalities on the prognosis. Eighty-seven AML patients were treated with HAD regimen containing intermediate dose cytarabine (IDAra-C) as induction therapy, 83 from which with karyotype results were divided into three cytogenetic groups according to SWOG criteria. Complete remission (CR) rate, disease-free survival (DFS), and overall survival (OS) among different groups were evaluated. The CR rate of the 87 cases was 80/87 (92%). Median DFS and OS have not reached (NR). DFS rates at 1 and 3 years were 76.3% and 63.4%, respectively. OS rates at 1 and 3 years were 86.0% and 58.7%, respectively. According to SWOG criteria, CR rate, median DFS, and OS were 100%, NR and NR for the favorable group; 88.9%, NR, and 16 months for the intermediate group; 83.3%, 4.5 months, and 7.5 months for the adverse group. The differences among the three groups were statistically significant excepting for CR rate between adverse and intermediate groups. HAD regimen containing IDAra-C as induction chemotherapy regimen is effective in de novo AML of adult patients and can achieve higher CR rate and longer survival than standard dose of cytarabine (SDAra-C) regimen. Most of the patients were able to endure the therapy. Cytogenetics is still an important prognostic factor despite of the incorporation of IDAra-C in induction chemotherapy. The differences among the three groups were statistically significant. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Using X-ray absorption spectra to monitor specific radiation damage to anomalously scattering atoms in macromolecular crystallographyACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2007V. Oliéric Radiation damage in macromolecular crystals is not suppressed even at 90,K. This is particularly true for covalent bonds involving an anomalous scatterer (such as bromine) at the `peak wavelength'. It is shown that a series of absorption spectra recorded on a brominated RNA faithfully monitor the extent of cleavage. The continuous spectral changes during irradiation preserve an `isosbestic point', each spectrum being a linear combination of `zero' and `infinite' dose spectra. This easily yields a good estimate of the partial occupancy of bromine at any intermediate dose. The considerable effect on the near-edge features in the spectra of the crystal orientation versus the beam polarization has also been examined and found to be in good agreement with a previous study. Any significant influence of the (C,Br bond/beam polarization) angle on the cleavage kinetics of bromine was also searched for, but was not detected. These results will be useful for standard SAD/MAD experiments and for the emerging `radiation-damage-induced phasing' method exploiting both the anomalous signal of an anomalous scatterer and the `isomorphous' signal resulting from its cleavage. [source] The Effects of Ascorbic Acid on Penicillin-induced Epileptiform Activity in RatsEPILEPSIA, Issue 7 2007Mustafa Ayyildiz Summary:,Purpose: Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as ,-tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin-induced epileptiform activity. Methods: A single microinjection of penicillin (2.5 ,l, 500 units, intracortically) into the left sensorimotor cortex induced epileptiform activity within 2,5 min, progressing to full seizure activity lasting ,3,5 h. In the first set of experiments, 30 min after penicillin injection, six different doses of ascorbic acid (25, 50, 100, 200, 400, or 800 mg/kg) were administered intraperitoneally (IP). The other group of animals received the effective dose of ascorbic acid (100 mg/kg, IP) for 7 days. Ascorbic acid administration was stopped 24 h before penicillin treatment. Another group of rats received the effective dose of ascorbic acid (100 mg/kg, IP) 30 min before penicillin treatment. In the second set of experiments, the lipid peroxidation (MDA) and reduced glutathione (GSH) levels of brain were measured in the control, control + ascorbic acid, penicillin, and penicillin + ascorbic acid groups. Results: Ascorbic acid, at the low dose (50, 100 mg/kg, 30 min after penicillin injection), decreased both the frequency and amplitude of penicillin-induced epileptiform activity in rats. Ascorbic acid, at intermediate doses (200, 400 mg/kg, 30 min after penicillin injection), decreased the frequency of epileptiform activity without changing the amplitude. Ascorbic acid, at the lowest dose (25 mg/kg) and highest dose (800 mg/kg) (30 min after penicillin injection), did not change either the frequency or amplitude of epileptiform activity. Ascorbic acid, at the low dose (100 mg/kg) was the most effective dose in changing the frequency and amplitude of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) 30 min before penicillin treatment caused a significant delay in the onset of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) for 7 days did not change the latency of epileptiform activity. The most effective dose of ascorbic acid (100 mg/kg) prevented both the decrease in GSH level and the increase in lipid peroxidation level (MDA) occurring after penicillin-induced epileptiform activity. Conclusions: These data indicate that ascorbic acid has neuroprotective activity against penicillin-induced epileptiform electrocorticogram activity. [source] The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma,HEMATOLOGICAL ONCOLOGY, Issue 4 2004E. Hatjiharissi Abstract The aim of the study was the evaluation of anti-angiogenic activity of the combination of intermediate doses of thalidomide and dexamethasone in patients with refractory/relapsed myeloma. Twenty-five patients were included in the study. Microvessel density (MVD) was evaluated in marrow biopsies before and after treatment. Serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-,), which have angiogenic potential and interleukin-6 (IL-6), IL-1,, soluble IL-6 receptor (sIL-6R), and transforming growth factor-beta (TGF-,) which are involved in the disease biology, were measured before treatment and then every 2 weeks for 8 weeks. Pretreatment levels of MVD, VEGF, b-FGF, IL-6, sIL-6R were increased in the patients compared to controls. The overall response rate to therapy was 72%. The administration of the combined regimen produced a significant reduction in MVD in responders. However, an increase in serum levels of VEGF, b-FGF, IL-6, sIL-6R was observed post-treatment in responders. In contrast, serum levels of TNF-,, TGF-,, IL-1, did not differ between patients and controls and remained unchanged during the study. These results suggest that the combination of thalidomide plus dexamethasone is an effective treatment for myeloma reducing MVD marrow levels but not serum levels of angiogenic cytokines or cytokines implicated in myeloma biology. Copyright © 2005 John Wiley & Sons, Ltd. [source] Pili bigemini complicating diode laser hair removalJOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2004E Kaniowska Summary After two diode laser treatments for hair removal, a 39-year-old woman was noted to have pili bigemini within the treated areas. It resolved after a third treatment. Pili bigemini, the appearance of two hairs coming from the same follicular opening, can be induced by intermediate doses of laser energy. It follows sublethal damage to the hair follicule apparatus. [source] Non-specific immune response of turbot, Scophthalmus maximus (L.), experimentally infected with a pathogenic Vibrio pelagiusJOURNAL OF FISH DISEASES, Issue 6 2003L Villamil Abstract The effect of a pathogenic Vibrio pelagius, isolated during a mass mortality of turbot larvae, on the non-specific immune response of turbot, Scophthalmus maximus (L.), macrophages was studied both in vitro and in vivo. The in vitro treatment of head kidney (HK) macrophages with viable V. pelagius caused a significant inhibition of the chemiluminescence (CL) response in comparison with untreated macrophages, while incubation with heat-killed bacteria did not affect this response. In vivo, the intraperitoneal injection of V. pelagius resulted in a significant inhibition of the CL response in infected fish at days 1 and 4 post-infection compared with the control fish response. The HK macrophage nitric oxide (NO) production was enhanced by in vitro incubation with intermediate doses of viable V. pelagius (5 × 103 and 5 × 104 bacteria mL,1) and higher doses of the heat-killed bacteria (5 × 104,5 × 106 bacteria mL,1). In both cases, the NO inhibitorN- , -nitro-L-arginine was capable of down-regulating the specific NO induction caused by incubation with the bacterial treatments. In contrast, incubation with ECPs at higher doses caused a reduction in NO production. In vivo, a significant enhancement in NO production was also observed in macrophage supernatants at day 10 post-infection. Lysozyme concentration in the serum was also significantly increased in the experimentally infected fish at days 4 and 10 post-injection. In addition, viable V. pelagius and its ECPs significantly reduced HK macrophage viability in vitro, whereas no significant differences in viability were observed during the incubation with heat-killed bacteria. As NO production was enhanced in the experimentally infected fish, the inhibitory effect of the NO donor, S-nitroso-acetyl-penicillamine (SNAP), was tested in vitro in a cell-free assay. The results showed that growth of V. pelagius was significantly inhibited using SNAP at a high concentration (1 mm). [source] Hypocretin-1 Dose-Dependently Modulates Maternal Behaviour in MiceJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006K. L. D'Anna Increases in neuronal activity of hypocretin (HCRT), a peptide involved in arousal, and in HCRT-1 receptor mRNA expression have recently been identified in association with lactation. HCRT is released within brain regions regulating maternal behaviour and it is possible that increased HCRT neurotransmission during lactation supports maternal care. The present study examined for the first time the behavioural effects of HCRT on lactating mice. At intermediate doses, intracerebroventricular (i.c.v.) injections of HCRT-1 (0.06 and 0.1 µg) elevated levels of licking and grooming of pups (but not self-grooming) and number of nursing bouts without affecting other behaviours. At the highest dose, HCRT-1 (0.3 µg, i.c.v) delayed latency to nurse, decreased nursing, increased time off nest, and decreased maternal aggression. Intraperitoneal injections of the HCRT-1 receptor antagonist, SB-334867, exhibited a general trend towards increasing time spent low-arched back nursing (P = 0.053) and decreasing licking and grooming of pups while high-arched back nursing (P = 0.052). This suggests that the endogenous release of HCRT, working independently or dependently with other neuromodulators, may be necessary for full maternal behaviour expression. Possible sites of HCRT action in enhancing and impairing maternal care were identified via examinations of c,Fos immunoreactivity in association with i.c.v. HCRT injections. Together, these finding support the idea of HCRT modulating maternal behaviour, with intermediate levels (0.06 and 0.1 µg) supporting (even augmenting) some behaviours, but with levels that are too high (0.3 µg HCRT, i.c.v.), maternal behaviour and aggression are suppressed. [source] The Relationship Between Vaccine Dose and Efficacy in Channel Catfish Ictalurus punctatus Vaccinated as Fry with a Live Attenuated Strain of Edwardsiella ictaluri (RE-33),JOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 2 2001David J. Wise Channel catfish Ictalurus punctatus were vaccinated at 12 d of age (post-hatch) by a 2-min bath immersion with attenuated Edwardsiella ictaluri RE-33 at doses of 2.5 × 105, 2.5 × 106, and 2.4 × 107 colony-forming units CFU/mL of water. Following vaccination, RE-33 was recovered from a greater percentage of fry that were vaccinated at the high and intermediate doses compared to fry vaccinated at the lowest dose. Independent of dose, the greatest percentage of RE-33 positive fry occurred between 1 and 6 d post-vaccination with a significant decrease in positive fry observed on day 12. A significant increase in mortality occurred 6 to 12 d post-vaccination in fry vaccinated at the highest dose. No differences in post-vaccination mortalities occurred between the other treatments. Following virulent E. ictaluri challenge, mortalities of fish vaccinated at doses of 2.5 × 106 and 2.4 × 107 CFU/mL were significantly less than those of fish vaccinated at 2.5 × 105 CFU/mL and sham-vaccinated control fish. These data show that vaccination with RE-33 can offer protection against subsequent virulent E. ictaluri infection. [source] | |||||||||||||