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Single Subcutaneous Injection (single + subcutaneous_injection)
Selected AbstractsModifying effect of propolis on dimethylhydrazine-induced DNA damage but not colonic aberrant crypt foci in ratsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005Rodrigo O. Alves de Lima Abstract Propolis is a honeybee product with several biological and therapeutic properties, including antimutagenic and anticarcinogenic activities. The effects of an aqueous extract of propolis (AEP) were evaluated on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) and DNA damage in the colon of male Wistar rats by the ACF and Comet assays, respectively. AEP was administered orally at 0.01%, 0.03%, 0.1%, and 0.3% in the drinking water, which resulted in doses of approximately 12, 34, 108, and 336 mg/kg body weight/day. Animals were also given a single subcutaneous injection of 40 mg/kg DMH and sacrificed 4 hr later for evaluating DNA damage, or 4 doses of 40 mg/kg DMH, administered 2 doses/week for 2 weeks, and sacrificed 12 weeks after the last injection for evaluating ACF development in the distal colon. Administration of AEP either simultaneously with or after the DMH treatment resulted in no statistically significant reduction of ACF. In contrast, 0.01%, 0.03%, and 0.3% AEP, given simultaneously with DMH, reduced DNA damage induction in the mid and distal colon. However, 0.3% AEP alone increased DNA damage in the colon. In conclusion, AEP had no effect on the formation of DMH-induced ACF in rat colon, but it modulated DMH-induced DNA damage in colon cells. Further investigations are recommended in order to establish the conditions under which propolis produces either protective or deleterious effects. Environ. Mol. Mutagen., 2005. © 2004 Wiley-Liss, Inc. [source] The vomeronasal organ is required for the expression of lordosis behaviour, but not sex discrimination in female miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Matthieu Keller Abstract The role of the vomeronasal organ (VNO) in mediating neuroendocrine responses in female mice is well known; however, whether the VNO is equally important for sex discrimination is more controversial as evidence exists for a role of the main olfactory system in mate recognition. Therefore, we studied the effect of VNO removal (VNOx) on the ability of female mice to discriminate between volatile and non-volatile odours of conspecifics of the two sexes and in different endocrine states using Y-maze tests. VNOx female mice were able to reliably distinguish between male and female or male and gonadectomized (gdx) male volatile odours. However, when subjects had to discriminate between male and female or gdx male non-volatile odours, VNOx females were no longer able to discriminate between sex or different endocrine status. These results thus show that the VNO is primarily involved in the detection and processing of non-volatile odours, and that female mice can use volatile odours detected and processed by the main olfactory system for mate recognition. However, VNO inputs are needed to promote contact with the male, including facilitation of lordosis responses to his mounts. A single subcutaneous injection with gonadotropin-releasing hormone (GnRH) partially reversed the deficit in lordosis behaviour observed in VNOx females suggesting that VNO inputs may reach hypothalamic GnRH neurons to influence the display of sexual behaviour. [source] Hippocampal granule neuron production and population size are regulated by levels of bFGFEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2002Yinghong Cheng Abstract Numerous studies of the proliferative effects of basic fibroblast growth factor (bFGF) in culture, including neonatal and adult hippocampal precursors, suggest that the factor plays a ubiquitous and life-long role in neurogenesis. In contrast, in vivo, bFGF is devoid of effects on neurons in mature hippocampus, raising the possibility that bFGF exhibits developmental stage-specific activity in the complex animal environment. To define neurogenetic effects in the newborn, a single subcutaneous injection of bFGF (20 ng/gm) was administered to postnatal day 1 (P1) rats, and hippocampal DNA content was quantified: bFGF elicited an increase in total DNA throughout adulthood, by 48% at P4, 25% at P22, and 17% at P180, suggesting that bFGF increases hippocampal cell number. To define mechanisms, bromodeoxyuridine (BrdU) was injected at P1 and mitotically labelled cells were assessed at P22: there was a twofold increase in BrdU-positive cells in the dentate granule cell layer (GCL), indicating that bFGF enhanced the generation of neurons, or neuronogenesis, from a cohort of precursors. Moreover, enhanced mitosis and survival led to a 33% increase in absolute GCL neuron number, suggesting that neuron production depends on environmental levels of bFGF. To evaluate this possibility, bFGF-knockout mice were analyzed: hippocampal DNA content was decreased at all ages examined (P3, ,42%; P21, ,28%; P360, ,18%), and total GCL neuron and glial fibrillary acidic protein (GFAP)-positive cell number were decreased by 30%, indicating that bFGF is necessary for normal hippocampal neurogenesis. We conclude that environmental levels of bFGF regulate neonatal hippocampal neurogenesis. As adult hippocampal neuronogenesis was unresponsive to bFGF manipulation in our previous study [Wagner, J.P., Black, I.B. & DiCicco-Bloom, E. (1999) J. Neurosci., 19, 6006], these observations suggest distinct, stage-specific roles of bFGF in the dentate gyrus granule cell lineage. [source] A Single-Dose Placebo-Controlled Study of AMG 162, a Fully Human Monoclonal Antibody to RANKL, in Postmenopausal WomenJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2004Pirow J Bekker Abstract The safety and bone antiresorptive effect of a single subcutaneous dose of AMG 162, a human monoclonal antibody to RANKL, was investigated in 49 postmenopausal women. AMG 162 is a potent antiresorptive agent for diseases such as osteoporosis. Introduction: RANKL is an essential osteoclastic differentiation and activation factor. Materials and Methods: The bone antiresorptive activity and safety of AMG 162, a fully human monoclonal antibody to RANKL, were evaluated in postmenopausal women in this randomized, double-blind, placebo-controlled, single-dose, dose escalation study. Six cohorts of eight to nine women were randomly assigned to receive a single subcutaneous injection of either AMG 162 or placebo (3:1 ratio). AMG 162 doses were 0.01, 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg. Subjects were followed up to 6 months in all cohorts and 9 months in the three highest dose cohorts. Second morning void urinary N-telopeptide/creatinine (NTX; Osteomark), serum NTX, and serum bone-specific alkaline phosphatase (BALP, Ostase) were assessed as bone turnover markers. Results and Conclusions: Forty-nine women were enrolled. A single subcutaneous dose of AMG 162 resulted in a dose-dependent, rapid (within 12 h), profound (up to 84%), and sustained (up to 6 months) decrease in urinary NTX. At 6 months, there was a mean change from baseline of ,81% in the 3.0 mg/kg AMG 162 group compared with ,10% in the placebo group; serum NTX changes were ,56% and 2%, respectively. BALP levels did not decrease remarkably until after 1 month, indicating that the effect of AMG 162 is primarily antiresorptive. Intact parathyroid hormone (PTH) levels increased up to ,3-fold after 4 days in the 3.0 mg/kg dose group, but returned toward baseline with follow-up. Albumin-adjusted serum calcium did not decrease >10% on average in any group, and no subject had values below 2 mmol/liter. AMG 162 was well tolerated. No related serious adverse events occurred. No clinically meaningful laboratory changes, other than those described above, were observed. In summary, a single subcutaneous dose of AMG 162 resulted in a dose-dependent rapid and sustained decrease from baseline in bone turnover and could be an effective and convenient treatment for osteoporosis. [source] Role of Gastrointestinal Hormones in Postprandial Reduction of Bone Resorption,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2003Dennis B Henriksen Abstract Collagen type I fragments, reflecting bone resorption, and release of gut hormones were investigated after a meal. Investigations led to a dose escalation study with glucagon like peptide-2 (GLP-2) in postmenopausal women. We found a dose-dependent effect of GLP-2 on the reduction of bone resorption. Introduction: The C-terminal telopeptide region of type I collagen as measured in serum (s-CTX) can be used to assess bone resorption. This marker of bone resorption has a significant circadian variation that is influenced by food intake. However, the mediator of this variation has not been identified. Materials and Methods: We studied the release of the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2; a representative of the intestinal proglucagon-derived peptides) after ingestion of glucose, fat, protein, and fructose, as well as their effects after parenteral administration in relation to bone turnover processes in healthy volunteers. Furthermore, we studied the effect on bone turnover of a single subcutaneous injection of GLP-2 in four different dosages (100, 200, 400, or 800 ,g GLP-2) or placebo in 60 postmenopausal women (mean age, 61 ± 5 years). Results: All macronutrients significantly (p < 0.05) reduced bone resorption as assessed by s-CTX (39,52% from baseline), and only the glucagon-like peptides were secreted in parallel. Parenteral administration of GIP and GLP-1 did not result in a reduction of the s-CTX level, whereas GLP-2 caused a statistically significant and dose-dependent reduction in the s-CTX level from baseline compared with placebo (p < 0.05). Urine DPD/creatinine, a marker of bone resorption, was significantly reduced by 25% from baseline in the 800-,g GLP-2 group (p < 0.01). An area under the curve (AUC0,8h) analysis for s-CTX after GLP-2 injection confirmed the dose-dependent decrease (ANOVA, p = 0.05). The s-osteocalcin level was unaffected by the GLP-2 treatment. Conclusion: These studies exclude both GIP and GLP-1 as key mediators for the immediate reduction in bone resorption seen after a meal. The dose-dependent reduction of bone resorption markers found after subcutaneous injection of GLP-2 warrants further investigation into the mechanism and importance of GLP-2 for the bone turnover processes. [source] Implication of Rho-associated kinase in the elevation of extracellular dopamine levels and its related behaviors induced by methamphetamine in ratsJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Minoru Narita Abstract A growing body of evidence suggests that several protein kinases are involved in the expression of pharmacological actions induced by a psychostimulant methamphetamine. The present study was designed to investigate the role of the Rho/Rho-associated kinase (ROCK)-dependent pathway in the expression of the increase in extracellular levels of dopamine in the nucleus accumbens and its related behaviors induced by methamphetamine in rats. Methamphetamine (1 mg/kg, subcutaneously) produced a substantial increase in extracellular levels of dopamine in the nucleus accumbens, with a progressive augmentation of dopamine-related behaviors including rearing and sniffing. Methamphetamine also induced the decrease in levels of its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA). Both the increase in extracellular levels of dopamine and the induction of dopamine-related behaviors by methamphetamine were significantly suppressed by pretreatment with an intranucleus accumbens injection of a selective ROCK inhibitor Y-27632. In contrast, Y-27632 had no effect on the decrease in levels of DOPAC and HVA induced by methamphetamine. Under these conditions, there were no changes in protein levels of membrane-bound RhoA in the nucleus accumbens following methamphetamine treatment. It is of interest to note that the microinjection of Y-27632 into the nucleus accumbens failed to suppress the increases in extracellular levels of dopamine, DOPAC, and HVA in the nucleus accumbens induced by subcutaneous injection of a prototype of µ-opioid receptor agonist morphine (10 mg/kg). Furthermore, perfusion of a selective blocker of voltage-dependent Na+ channels, tetrodotoxin (TTx) into the rat nucleus accumbens did not affect the increase in extracellular levels of dopamine in the rat nucleus accumbens by methamphetamine, whereas the morphine-induced dopamine elevation was eliminated by this application of TTx. The extracellular level of dopamine in the nucleus accumbens was also increased by perfusion of a selective dopamine re-uptake inhibitor 1-[2-[bis(4-fluorophenyl)methoxy]-4-(3-phenylpropyl)piperazine (GBR-12909) in the nucleus accumbens. This effect was not affected by pretreatment with intranucleus accumbens injection of Y-27632. These findings provide first evidence that Rho/ROCK pathway in the nucleus accumbens may contribute to the increase in extracellular levels of dopamine in the nucleus accumbens evoked by a single subcutaneous injection of methamphetamine. In contrast, this pathway is not essential for the increased level of dopamine in this region induced by morphine, providing further evidence for the different mechanisms of dopamine release by methamphetamine and morphine in rats. [source] Clinical efficacy of diclofenac sodium and flunixin meglumine as adjuncts to antibacterial treatment of respiratory disease of calvesAUSTRALIAN VETERINARY JOURNAL, Issue 6 2010M Guzel Objective To compare the efficacy of the non-steroidal antiinflammatory drugs, diclofenac sodium and flunixin meglumine as adjuncts to the antibiotic treatment of bovine respiratory disease (BRD). Procedure We randomly allocated 80 Holstein calves with BRD to three groups. All the calves received a dose of 2.5 mg/kg tulathromycin by single subcutaneous injection and two of the groups received, in addition, either 2.5 mg/kg diclofenac sodium as a single intramuscular injection (diclofenac group, n = 30) or 2.2 mg/kg flunixin meglumine as an intravenous injection on the first three consecutive days after tulathromycin administration (flunixin group, n = 30). All calves were given a clinical score prior to initial treatment (day 0) and after treatment (days 1, 2, 3, 7 and 14) by observing appetite, demeanour, rectal temperature, the rate and type of respiration, presence or absence of coughing, and nasal discharge. Results During the first 48 h, improvement of adverse signs of respiratory disease, such as pyrexia and elevated respiratory rate, and of a high clinical index score was significant in the two adjunct groups compared with the calves receiving antibiotic alone. The reduction in pyrexia was greatest in the diclofenac group. There were no statically significant differences between treatment groups with regard to eventual perceived recovery from respiratory disease in 14 days. Conclusion In this trial, a single intramuscular dose of diclofenac sodium was equally effective as three intravenous injections of flunixin meglumine given on consecutive days as adjunctive therapy for BRD. [source] Clinical Pathology Alterations in Pregnant and Non-Pregnant Rats following Scorpion EnvenomationBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009Hmed Ben Nasr Existing diagnostic criteria are not sufficiently specific to allow antivenin administration in the absence of a confirmed scorpion sting. This study was performed to evaluate conventional haematological and serum chemical measurements as potential indices of scorpion envenomation. Adult, cycling nulliparous and near-term primiparous, white Wistar rats received a single subcutaneous injection of crude venom (600 µg/kg) from the Buthidae scorpion (Buthus occitanus tunetanus). All envenomed rats were observed for external signs and symptoms of toxicity until necropsy, which entailed terminal blood collection at either 0.5, 1, 2, or 4 hr after venom administration (n = 6 per reproductive state per time-point) for evaluation of selected clinical chemistry and haematological analytes. Control cohorts (matched for age and reproductive state) received saline injections subcutaneously and were necropsied at 0.5 hr. Almost all envenomed rats but no control animals displayed physical symptoms of intoxication, including agitation, mastication with hypersalivation, and/or vocalizing. Reproducible alterations in clinical pathology parameters were lacking in venom-treated rats regardless of reproductive status, although modest but significant Rho correlations suggested that mild haemoconcentration, haemolysis, renal function deficits and possibly coagulation difficulties developed over time. [source] Pulsed electromagnetic fields accelerate wound healing in the skin of diabetic ratsBIOELECTROMAGNETICS, Issue 4 2010Iran Goudarzi Abstract Delayed wound healing is a common complication in diabetes mellitus. From this point of view, the main purpose of the present study is to investigate the effect of extremely low frequency pulsed electromagnetic fields (ELF PEMFs) on skin wound healing in diabetic rats. In this study, diabetes was induced in male Wistar rats via a single subcutaneous injection of 65,mg/kg streptozocin (freshly dissolved in sterile saline, 0.9%). One month after the induction of diabetes, a full-thickness dermal incision (35,mm length) was made on the right side of the paravertebral region. The wound was exposed to ELF PEMF (20,Hz, 4,ms, 8,mT) for 1,h per day. Wound healing was evaluated by measuring surface area, percentage of healing, duration of healing, and wound tensile strength. Obtained results showed that the duration of wound healing in diabetic rats in comparison with the control group was significantly increased. In contrast, the rate of healing in diabetic rats receiving PEMF was significantly greater than in the diabetic control group. The wound tensile strength also was significantly greater than the control animals. In addition, the duration of wound healing in the control group receiving PEMF was less than the sham group. Based on the above-mentioned results we concluded that this study provides some evidence to support the use of ELF PEMFs to accelerate diabetic wound healing. Further research is needed to determine the PEMF mechanisms in acceleration of wound healing in diabetic rats. Bioelectromagnetics 31:318,323, 2010. © 2010 Wiley-Liss, Inc. [source] Clinical trial: the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome: a randomized, placebo-controlled, double-blind studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009P. M. HELLSTRÖM Summary Background, There is currently no treatment available to manage acute pain attacks in IBS patients regardless of subtype. Aims, To evaluate efficacy and safety of the GLP-1 analogue ROSE-010 in patients with irritable bowel syndrome (IBS) through a randomized, double-blind, placebo-controlled study. Methods, Eligible patients (n = 166) meeting Rome II criteria were randomly assigned to receive single subcutaneous injections of ROSE-010 100 ,g, 300 ,g and placebo in a cross-over design. Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Patient-rated pain relief and intensity were measured on a 100-mm visual analogue scale. The primary efficacy variable was proportion of patients with >50% maximum total pain relief response from 10 to 60 min after treatment. Secondary endpoints included the maximum summed pain intensity difference, time to meaningful pain relief and patient ratings of satisfaction with treatment. Results, Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo (24%P = 0.011, 23%P = 0.005, and 12% after 300 ,g, 100 ,g and placebo injections, respectively). Similar results were obtained for the proportion of patients with total pain intensity response. Times to meaningful and total pain relief were shorter for both doses of ROSE-010 compared with placebo. Compared with placebo, more patients (P < 0.05) were satisfied with ROSE-010 and considered ROSE-010 better than previous IBS medications used. Conclusion, ROSE-010 was well tolerated and provided fast and effective relief of acute pain attacks on demand in IBS patients. [source] | |||||||||||||