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G Doses (g + dose)
Selected AbstractsDissociable effects of cocaine-seeking behavior following D1 receptor activation and blockade within the caudal and rostral basolateral amygdala in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Yasmin Mashhoon Abstract Research with dopamine D1 receptor antagonists or neuronal inactivating agents suggests that there is dissociable regulation of cocaine-seeking behavior by the rostral and caudal basolateral amygdala. In the present study, discrete infusions of the D1 receptor agonist SKF 81297 (0.0,0.8 ,g per side) were compared with those of the D1 receptor antagonist SCH 23390 (0.0,2.0 ,g per side) to demonstrate directly the importance of D1 receptor mechanisms within the rostral and caudal basolateral amygdala for their functional heterogeneity in regulating cocaine-seeking behavior. Under a second-order schedule, cocaine-seeking behavior was studied during maintenance (cocaine and cocaine cues present) and reinstatement (only cocaine cues present). Food-maintained responding was used to examine the specificity of maximal behaviorally effective doses of SKF 81297 and SCH 23390. The results demonstrated that the D1 agonist (0.4 or 0.8 ,g) increased and the D1 antagonist (1.0 ,g) decreased cocaine-seeking behavior during maintenance when infused into the caudal but not the rostral basolateral amygdala. Cocaine intake was not affected by the agonist, and was decreased by the antagonist. During reinstatement, the D1 agonist (0.4 ,g) increased and the D1 antagonist (1.0 ,g) decreased cocaine-seeking behavior when infused into the rostral but not the caudal basolateral amygdala. In tests for behavioral specificity, the above effective doses of SKF 81297 and SCH 23390 used in self-administration experiments did not alter food-maintained responding. However, the 2.0-,g dose of SCH 23390 suppressed drug-maintained and food-maintained responding after infusion into both subregions. Collectively, these findings indicate dissociable sensitivity to D1 receptor ligands within the caudal and rostral basolateral amygdala for altering cocaine-seeking behavior under different conditions that model phases of addiction. [source] A porcine model for fixed drug eruptions in humans: the case of antipyrine in the Yucatan micropigJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2006Yvonne Pak Abstract To date, there is no acceptable animal model to investigate fixed drug eruptions (FDEs) in humans. We briefly report here observations suggesting that the Yucatan micropig may be a useful animal model for that purpose. During an investigation of antipyrine absorption and disposition, we observed the development of FDEs after intravenous administration of a 1 g dose. Our observations were consistent with those reported in several investigations of humans taking a single dose of antipyrine. To confirm these results, a naïve micropig was challenged. A male uncastrated Yucatan micropig (27.2 kg) was given a 1 g dose of antipyrine intravenously. After 30 days, this pig was rechallenged with the same intravenous dose of antipyrine (1 g). Blood samples were obtained to examine immunological endpoints. During the initial challenge, a fluid plaque (ca. 1,1.5 cm) appeared on the left hip of the pig ca. 6 h after dosing. After the rechallenge, inflamed pink patches were observed at the same sites where the blisters formed initially; however, no blisters re-formed. Changes of neutrophil, lymphocyte and eosinophil levels from baseline were noted 8 h after challenge. The micropig did not seem otherwise affected by the FDEs. These observations suggest that the Yucatan micropig, or swine in general, may be a useful animal model for detecting drugs that may cause FDEs in humans. Copyright © 2005 John Wiley & Sons, Ltd. [source] Bone formation at rhBMP-2-coated titanium implants in the rat ectopic modelJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2007Jan Hall Abstract Background: The objective of this study was to evaluate local bone formation at titanium porous oxide (TPO) implant surfaces adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2). Methods: In vitro studies were used to estimate the kinetics of I125 -labeled rhBMP-2 released from TPO surfaces with narrow (N) or open (O) pores. Machined/turned titanium (MT) surfaces served as control. The rat ectopic model was used to assess local bone formation. Briefly, TPO-N, TPO-O, and MT disc implants adsorbed with 5, 10, or 20 ,g rhBMP-2, respectively, were implanted subcutaneously into the ventral thoracic region in 5-week-old male Long Evans rats. The animals were euthanized at day 14 postsurgery when implants with surrounding tissues were removed, radiographed, and gross observations recorded. The specimens were processed for histologic evaluation using conventional cut-and-grind techniques. TPO implants without rhBMP-2 included in a preliminary evaluation revealed no evidence of bone formation, tissue encapsulation, or vascularity, thus such controls were not further used. Results: TPO and MT implant surfaces adsorbed with 5 ,g rhBMP-2 retained 2.3,5.4% rhBMP-2 following immersion and rinse in buffer, and 1.1,2.2% rhBMP-2 following repeated immersions and rinses over 27 days. TPO implants retained the most rhBMP-2 and MT implants retained the least. Explants revealed increased hard tissue formation, tissue encapsulation, and vascularity at TPO compared with MT implants. Radiographic observations were consistent with the explant observations. The histologic analysis showed greater amounts of bone formation, osteoblastic cells, osteoid, marrow, tissue encapsulation, vascularity, and bone voids for implants adsorbed with 10 and 20 ,g rhBMP-2, and for TPO implants at the 5- ,g rhBMP-2 dose. The histometric analysis revealed significantly greater bone formation at TPO-O than at MT implants at the 5- ,g rhBMP-2 dose. All surfaces showed significant bone formation at the 10- and 20- ,g dose. Conclusions: rhBMP-2 adsorbed onto TPO implant surfaces executes an osteoinductive effect including bone contacting the implant surface. This effect is surface- and dose-dependent; the TPO-O surface yielding the most bone at the low discriminating rhBMP-2 dose. [source] Cortisol response to two different doses of intravenous synthetic ACTH (tetracosactrin) in overweight catsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 12 2000J. P. Schoeman Fifteen middle-aged to older, overweight cats attending a first-opinion clinic were investigated to rule out hyperadrenocorticism as a cause of their weight problem, using two different protocols for the adrenocortlcotropic hormone (ACTH) stimulation test. The cats received intravenous synthetic ACTH (tetracosactrin) at an initial dose of 125 ,g; a second test was performed between two and three weeks later, using a dose of 250 vg intravenously. The mean basal serum cortisol concentration was 203 nmol/litre (range 81 to 354 nmol/litre). The highest mean serum cortisol concentration occurred at 60 minutes following the 125 ,g dose and at 120 minutes following the 250 ,g dose. There was, however, no statistically significant difference between these peak cortisol concentrations attained using either dose of tetracosactrin. A significantly higher mean serum cortisol concentration was attained after the higher dose at the 180 minutes time point, indicating a more prolonged response when compared with the lower dose. The cats were followed up for one year after the initial investigations and none were found to develop hyperadrenocorticism during this time. [source] Original Article: Treatment: Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trialDIABETIC MEDICINE, Issue 9 2010R. E. Ratner Diabet. Med. 27, 1024,1032 (2010) Abstract Aims, To evaluate the dose,response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. Methods, Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) , 7.0 and < 9.0% (, 53 and < 75 mmol/mol)] on metformin (, 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 ,g once daily or twice daily or placebo. The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population. Results, Lixisenatide significantly improved mean HbA1c from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 ,g doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P < 0.01 vs. placebo). Target HbA1c < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 ,g once-daily lixisenatide vs. 32% receiving placebo (P < 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from ,2.0 to ,3.9 kg with lixisenatide vs. ,1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. Conclusions, Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose,response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 ,g once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies. [source] Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor-5: histologic observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2010Giuseppe Polimeni Polimeni G, Wikesjö UME, Susin C, Qahash M, Shanaman RH, Prasad HS, Rohrer MD, Hall J. Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor-5: histologic observations. J Clin Periodontol 2010; 37: 759-768 doi: 10.1111/j.1600-051X.2010.01579.x. Abstract Objectives: In vitro and in vivo preclinical studies suggest that growth/differentiation factor-5 (GDF-5) may induce local bone formation. The objective of this study was to evaluate the potential of recombinant human GDF-5 (rhGDF-5) coated onto an oral implant with a purpose-designed titanium porous oxide surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Materials and Methods: Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with 30 or 60 ,g rhGDF-5, and six animals received implants coated with 120 ,g rhGDF-5 or left uncoated (control). Treatments were alternated between jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7, and 8 post-surgery when they were euthanized for histologic evaluation. Results: The clinical examination showed no noteworthy differences between implants coated with rhGDF-5. The cover screw and implant body were visible/palpable through the alveolar mucosa for both rhGDF-5-coated and control implants. There was a small increase in induced bone height for implants coated with rhGDF-5 compared with the control, induced bone height averaging (±SD) 1.6±0.6 mm for implants coated with 120 ,g rhGDF-5 versus 1.2±0.5, 1.2±0.6, and 0.6±0.2 mm for implants coated with 60 ,g rhGDF-5, 30 ,g rhGDF-5, or left uncoated, respectively (p<0.05). Bone formation was predominant at the lingual aspect of the implants. Narrow yellow and orange fluorescent markers throughout the newly formed bone indicate relatively slow new bone formation within 3,4 weeks. Implants coated with rhGDF-5 displayed limited peri-implant bone remodelling in the resident bone; the 120 ,g dose exhibiting more advanced remodelling than the 60 and 30 ,g doses. All treatment groups exhibited clinically relevant osseointegration. Conclusions: rhGDF-5-coated oral implants display a dose-dependent osteoinductive and/or osteoconductive effect, bone formation apparently benefiting from local factors. Application of rhGDF-5 appears to be safe as it is associated with limited, if any, adverse effects. [source] Repair of rabbit segmental defects with the thrombin peptide, TP508JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004Michael R. Sheller Abstract The synthetic peptide, TP508 (Chrysalin®), was delivered to rabbit segmental bone defects in biodegradable controlled-release PLGA microspheres to determine its potential efficacy for enhancing healing of non-critically and critically sized segmental defects. Non-critically sized radial defects were created in the forelimbs of New Zealand White rabbits, which were randomized into three treatment groups receiving 10, 50 and 100 ,g doses of TP508 in the right radius and control microspheres (without TP508) in the left radius. Torsional testing of the radii at six weeks showed a significant increase in ultimate torque, failure torque, ultimate energy, failure energy, and stiffness when treated with TP508 compared to controls (p < 0.01 for all measures). Thus, TP508 appeared to enhance or accelerate bone growth in these defects. In a second set of experiments, critically sized ulnar defects were created in the forelimbs of New Zealand White rabbits, which were randomized into two groups with each rabbit receiving microspheres with 100 or 200 ,g of TP508 into the right ulnar defect and control microspheres (without TP508) alone into the left ulnar defect. Bone healing was evaluated with plain radiographs, synchrotron-based microtomography, and mechanical testing. Radiographs of the rabbit limbs scored by three blinded, independent reviewers demonstrated a significantly higher degree of healing when treated with TP508 than their untreated control limbs (p < 0.05). Three-dimensional synchrotron tomography of a limited number of samples showed that the new bone in TP508-treated samples had a less porous surface appearance and open marrow spaces, suggesting progression of bone remodeling. Torsional testing of the ulnae at nine weeks showed a significant increase in maximum torque and failure energy when treated with TP508 compared to controls (p < 0.01 for both measures). These results suggest that TP508 in a controlled release delivery vehicle has the potential to enhance healing of segmental defects in both critically and non-critically sized defects. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Vaccination against hepatitis B virus in cirrhotic patients on liver transplant waiting listLIVER TRANSPLANTATION, Issue 4 2000Mercedes Domínguez Patients with cirrhosis may fail to respond to anti,hepatitis B vaccine. An adequate response would be especially interesting when patients are on a liver transplant waiting list. Posttransplantation de novo hepatitis B has been well documented. One possible source is the grafting of organs from hepatitis B surface antigen (HBsAg),negative, antibody to HBsAg (anti-HBs),positive, antibody to hepatitis B core antigen,positive donors. The achievement of high titers of anti-HBs could be protective in this setting. We studied prospectively the response rate to recombinant hepatitis B vaccine (3 40-,g doses administered at 0, 1, and 2 months) in 62 patients with end-stage liver disease awaiting liver transplantation. Twenty-two patients showed antibody response (44%). A further 3 doses were administered in 15 of 28 nonresponders and were effective in 9 patients. Thus, the response rate reached 62% (31 of 50 patients completing 1 or 2 vaccination schedules before liver transplantation). Classic hepatitis B vaccination studies of patients with cirrhosis yield lower response rates. Vaccination with this double-dose schedule should be considered in such patients before liver transplantation. [source] Identification of feeding attractants in oak sap for adults of two nymphalid butterflies, Kaniska canace and Vanessa indicaPHYSIOLOGICAL ENTOMOLOGY, Issue 3 2000Hisashi Ômura Abstract The active compounds of oak-sap odour in attracting adults of two butterflies, Kaniska canace (L.) and Vanessa indica (Herbst) (Lepidoptera: Nymphalidae), were identified by chemical analyses, electroantennogram (EAG) and two behavioural assays: proboscis extension reflex (PER) and attraction to artificial tree models. Fourteen compounds were identified from two sap samples collected in 1997 and 1998, of which the major volatiles were ethanol and acetic acid (, 900 p.p.m. and 500 p.p.m. in sap, respectively). However, the chemical composition of the minor volatiles varied considerably between the two samples. Among 13 chemicals tested, V. indica showed strong PER to five aliphatic acids (acetic, propionic, butyric, isobutyric and isovaleric), 2-methylpropan-1-ol and 3-hydroxybutan-2-one, whereas the PER-active compounds for K. canace were these seven compounds and also ethanol, 3-methylbutan-1-ol and 1-hydroxypropan-2-one. In two-choice behavioural bioassays, the model scented with a sap-odour mimic, which was an aqueous mixture of the PER-active compounds, was more attractive to the two butterflies than an unscented control. These results demonstrated that the sap odour stimulates foraging behaviour of the butterfly. Although EAG responses of both butterflies to 3-methylbutan-1-ol and that of V. indica to 2-methylpropan-1-ol were positively dose-dependent, responses to other compounds were not strong and not dose-dependent at 1,100 ,g doses. These EAG responsiveness suggests that the olfactory receptors for these compounds might be few in the antenna and that the butterflies have enough olfactory sensitivity to the dose of 1 ,g. [source] Toxicity and Synergism in the Feeding Deterrence of Some Coumarins on Spodoptera frugiperdaSmith (Lepidoptera: Noctuidae)CHEMISTRY & BIODIVERSITY, Issue 1 2006Nancy Vera Abstract The phagodepression activity of five coumarins (=2H -1-benzopyran-2-ones), 6-hydroxy-7-isoprenyloxycoumarin (1), 6-methoxy-7-isoprenyloxycoumarin (2), 6,7-methylenedioxycoumarin (3), 5-methoxy-6,7-methylenedioxycoumarin (4), and 6-methoxy-7-(2-hydroxyethoxy)coumarin (5), from the Argentine native herb Pterocaulon polystachyum, was tested against Spodoptera frugiperda (Lepidoptera: Noctuidae) larvae. Two analogs, scopoletin (6) and 2-methoxy-2-methyl-3,4,5,6,7,8-hexahydro-3H -chromen-5-one (7), synthesized in our laboratory, were also evaluated for comparison. The compounds were added to an artificial diet at doses ranging from 50 to 200,,g per g of diet. Natural coumarins induced 100% of phagodepression when 200,,g were added per g of diet. Binary equimolar mixtures of the natural coumarins were phagodepressors against S. frugiperda surpassing the expected additive responses, indicating that these compounds can act synergistically against S. frugiperda larvae. Compounds 1 and 3 (non-methoxylated coumarins), and the equimolar mixture of both, displayed the strongest phagodepression. Additionally, 50,,g/g of 1 and 3 incorporated to the larval diet caused 80 and 50% of pupal mortality, respectively, while a 100,,g/g dose of compounds 2, 4, 6, and 7 produced 60, 50, 10, and 80% pupal mortality, respectively. Larval growing rate during the early larval instars was significantly reduced by treatments with the methylenedioxycoumarins 3 and 4. Coincidentally, the larval period duration was significantly increased by the latter compounds. [source] The role of thyroid hormone on phenylhydrazine hydrochloride mediated inhibitory effects on blood acetylcholinesterase: An in vivo and in vitro studyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2002Mitali Banerjee Abstract A novel phenomenon of protective counteraction by thyroid hormone has been demonstrated in phenylhydrazine hydrochloride (PHH) induced insult on blood acetylcholinesterase (AChE, EC 3.1.1.7) activity, in both, in vivo and in vitro conditions. Injection of PHH (20 ,g/g) to juvenile male rats for three consecutive days caused a 48% decrease (p < 0.001) in the total blood AChE activity on the third day (i.e. 24 h after injections for three consecutive days) in comparison to the control animals. Simultaneous injections of thyroxine (T4) 1 or 2 ,g/g with PHH (20 ,g/g) showed a recovery in AChE activity by 27% (p < 0.02) and 55% (p < 0.001), respectively, in comparison to the only PHH-injected animals. T4 at 1, 2 and 4 ,g/g doses showed unchanged levels in comparison to the untreated controls. In our in vitro system, incubations of the RBCs in PHH (2 mM) containing medium also showed an inhibition of 44% (p < 0.001) of the RBC membrane AChE activity in comparison to the control conditions. A recovery of 23,81% of the enzyme activity was observed after simultaneous use of T4 (1 nM,100 nM) or T3 (0.1 nM,100 nM), or triiodothyroacetic acid (TRIAC) (100 nM) with PHH (2 mM) in a dose-dependent manner with a potency profile of T3 > T4 > TRIAC. Incubation of RBCs only with T4, T3, or TRIAC at 0.1,100 nM concentration did not cause any alteration in the membrane AChE activity in comparison to control conditions. Thus, thyroid hormone distinctly demonstrated a counteraction or protective nature of action on the PHH-induced inhibition of total blood and RBC membrane AChE activity. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:162,168, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10039 [source] | ||||||||||||||||