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Subcutaneous Injection (subcutaneous + injection)
Kinds of Subcutaneous Injection Selected AbstractsSubcutaneous Injection of Anakinra in Patients with Shoulder Pain Due to Rotator Cuff Tendonitis and Subacromial BursitisPAIN MEDICINE, Issue 2 2004Sota Omoigui MD No abstract is available for this article. [source] GAD65 autoantibody epitopes in adult patients with latent autoimmune diabetes following GAD65 vaccinationDIABETIC MEDICINE, Issue 5 2007L. M. Bekris Abstract Aims Subcutaneous injection of recombinant human GAD65 (rhGAD65) in patients with latent autoimmune diabetes in adults (LADA) correlates with an increase in C-peptide levels. In this study we analysed the effect of rhGAD65 administration on the GAD65-specific autoimmune response. Methods Longitudinal serum samples obtained from LADA patients (n = 47) who received 4, 20, 100 or 500 µg alum-formulated rhGAD65 or placebo by subcutaneous injection twice (4 weeks apart) were analysed for their epitope recognition using GAD65-specific recombinant Fab and GAD65/67 fusion proteins. Results Overall, minor changes in the epitope pattern were observed using either approach. Only in the 500-µg dosage group was an increase in GAD65Ab level associated with a significant increase in the binding to a conformational epitope located at the middle part of GAD65. Conclusions Our data suggest that the apparent beneficial effects of 20 µg alum-formulated recombinant human GAD65 is not explained by changes in the GAD65Ab epitope pattern. [source] Sertraline, a selective serotonin reuptake inhibitor, affects thirst, salt appetite and plasma levels of oxytocin and vasopressin in ratsEXPERIMENTAL PHYSIOLOGY, Issue 5 2007Ana Paula De Magalhães-Nunes We investigated the effects of chronic administration of sertraline (SERT; ,20 mg kg,1 day,1 in drinking water), a selective serotonin reuptake inhibitor, on water and sodium intake and on plasma levels of oxytocin (OT) and vasopressin (AVP) in basal and stimulated conditions. Basal water intake was reduced in SERT-treated rats. After 24 h of water deprivation, rats treated with SERT for 21 days ingested less water than the control rats (9.7 ± 0.5 versus 20.0 ± 0.9 ml, respectively, at 300 min after water presentation, P < 0.0001). Subcutaneous injection of 2 m NaCl or isoproterenol evoked a lower dipsogenic response in rats treated with SERT for 21 days. Fluid and food deprivation also induced a weaker dipsogenic response in SERT-treated rats (1.6 ± 0.5 versus 10.2 ± 1.2 ml, at 300 min, P < 0.0001) but had no effect on saline intake. Sodium depletion induced a higher natriorexigenic response in the SERT group (5.6 ± 1.3 versus 1.2 ± 0.3 ml, at 300 min, P < 0.0002). Higher urinary density and lower plasma sodium levels were observed after SERT treatment. Sertraline also increased plasma levels of vasopressin and oxytocin (AVP, 2.65 ± 0.36 versus 1.31 ± 0.16 pg ml,1, P < 0.005; OT, 17.16 ± 1.06 versus 11.3 ± 1.03 pg ml,1, P < 0.0009, at the third week post-treatment). These data constitute the first evidence that chronic SERT treatment affects water and sodium intake in rats. These effects seem to be related to the hyponatraemia caused by the higher plasma levels of AVP and OT. [source] Further characterization of human fetal osteoblastic hFOB 1.19 and hFOB/ER, cells: Bone formation in vivo and karyotype analysis using multicolor fluorescent in situ hybridizationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2002M. Subramaniam Abstract We have previously generated an immortalized human fetal osteoblastic cell line (hFOB) using stably transfected temperature sensitive SV40 T-antigen (Harris et al. [1995a] J. Bone. Miner. Res. 10:178,1860). To characterize these cells for phenotypic/genotypic attributes desired for a good cell model system, we performed karyotype analysis by multicolor fluorescent in situ hybridization (M-FISH), their ability to form bone in vivo without developing cell transformation, and finally their ability to form extracellular matrix formation in vitro. The karyotype analysis of hFOB cells revealed structural or numeric anomalies involving 1,2 chromosomes. In contrast, the human osteosarcoma MG63 cells displayed multiple, and often complex, numeric, and structural abnormalities. Subcutaneous injection of hFOB cells in the presence of Matrigel into nude mice resulted in bone formation after 2,3 weeks. Electron microscopic analysis of the extracellular matrix deposited by hFOB cells in culture revealed a parallel array of lightly banded fibrils typical of the fibrillar collagens such as type I and III. These results demonstrate that the hFOB cell line has minimal chromosome abnormalities, exhibit the matrix synthetic properties of differentiated osteoblasts, and are immortalized but non-transformed cell line. These hFOB cells thus appear to be an excellent model system for the study of osteoblast biology in vitro. J. Cell. Biochem. 87: 9,15, 2002. © 2002 Wiley-Liss, Inc. [source] Gadobenate dimeglumine as a contrast agent for MRI of the mouse liverNMR IN BIOMEDICINE, Issue 8 2007Yusuke Inoue Abstract We investigated the characteristics and utility of gadobenate dimeglumine (Gd-BOPTA) for MRI of the mouse liver. Mice were imaged under isoflurane anesthesia using a T1 -weighted, three-dimensional fast low-angle shot (3D FLASH) sequence before and after intravenous or subcutaneous injection of Gd-BOPTA, and the time course of the contrast effect was examined. The appropriate dose for subcutaneous injection was determined visually, and the inter- and intra-observer reproducibilities in liver volumetry were evaluated with and without contrast injection. When mice were imaged sequentially before and after Gd-BOPTA injection and isoflurane anesthesia was maintained throughout the experiment, a long-lasting contrast effect was noted in the liver. Subcutaneous injection caused delayed, but favorable, enhancement. Washout from the liver was definitely accelerated in conscious mice in comparison with anesthetized mice. Visual evaluation indicated that a dose of 0.1,mmol/kg was appropriate for clear delineation of the entire liver margin, and the application of Gd-BOPTA significantly improved the inter- and intra-observer reproducibilities of liver volumetry. In conclusion, the intravenous or subcutaneous injection of Gd-BOPTA has a favorable contrast effect for the mouse liver, resulting in clear visualization of the liver border and improved reproducibility of liver volumetry. The possible influence of anesthesia on the pharmacokinetics of a contrast agent should be considered in determining the optimal scan timing. Copyright © 2007 John Wiley & Sons, Ltd. [source] Role of Cholecystokinin Receptors in Induction of Antinociception in Hot-Plate TestBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2000Mehdi Rezayat In the present study, the antinociceptive effect of cholecystokinin receptor agonists in the hot-plate test in mice has been evaluated. Subcutaneous administration of cholecystokinin octapeptide (cholecystokinin-8; 0.001, 0.005, 0.01, 0.05, and 0.1 mg/kg), unsulfated cholecystokinin octapeptide (cholecystokinin-8U; 0.1 mg/kg) or caerulein (0.25 mg/kg) produced antinociception. Administration of the cholecystokinin tetrapeptide (cholecystokinin-4; 0.25, 0.5 and 1.0 mg/kg) had no effect in the hot-plate test. Subcutaneous injection of the selective cholecystokinin receptor antagonists, MK-329 (0.125, 0.25 and 0.5 mg/kg) or L-365,260 (0.125, 0.25 and 0.5 mg/kg), produced no antinociceptive response. When the animals were pretreated with the cholecystokinin receptor antagonists or naloxone (0.5 and 1 mg/kg), a significant decrease in the antinociceptive response induced by cholecystokinin-8 and caerulein was obtained. The results indicate that single administration of cholecystokinin receptor agonists could produce an antinociceptive effect which is probably mediated via cholecystokinin receptors. With respect to the results obtained from morphine and naloxone administration, it is concluded that there may be an interaction between cholecystokinin and opiate mechanisms. [source] Thyroid cancer immuno-therapy with retroviral and adenoviral vectors expressing granulocyte macrophage colony stimulating factor and interleukin-12 in a rat modelCLINICAL ENDOCRINOLOGY, Issue 6 2003Kunihiko Tanaka Summary background, Introduction of genes encoding immuno-stimulatory cytokine(s) into cancer cells is well known to enhance anti-tumour immunity. aim, The present studies were designed to evaluate the therapeutic efficacy of retroviral- and adenoviral-mediated delivery of IL-12 and/or granulocyte macrophage colony-stimulating factor (GM,CSF) genes for thyroid cancer in an immuno-competent rat model. methods, A rat thyroid cancer cell line FRTL-Tc syngeneic to Fisher rat was used. results, Expression of these exogenous cytokines did not affect in vitro cell growth. Subcutaneous injection of FRTL-Tc cells retrovirally transduced with IL-12 or GM,CSF genes formed significantly smaller tumours than that of the parental cells, but had little effect on growth of distant tumours, suggesting no vaccine effect. Similarly, injection of the cells infected with adenovirus expressing IL-12 or GM,CSF (AdIL-12 or AdGM,CSF) almost completely abolished tumourigenicity and injection of AdGM,CSF into pre-established tumours significantly inhibited growth of the tumours injected; neither, however, showed a systemic vaccine affect. On the other hand, injection of AdIL-12 into the pre-established tumours significantly inhibited growth of not only the tumours injected but also distant tumours, indicating induction of systemic anti-tumour immunity. Serum IL-12 was detectable only in this approach. There was neither a synergistic or additive effect of these two cytokines. conclusions, Our data demonstrate in a rat thyroid cancer model that only injection of AdIL-12 into the pre-established tumours elicited systemic anti-tumour immunity, but injection of AdGM,CSF or injection of the cells expressing IL-12 or GM,CSF elicited only local effect, indicating that in situ delivery of IL-12 gene with adenovirus appears most efficacious but may still require adjuvant modalities to enhance the anti-tumour effect. [source] Golimumab, a human anti,tumor necrosis factor , monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: Twenty-four,week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis,ARTHRITIS & RHEUMATISM, Issue 8 2009Paul Emery Objective To assess the safety and efficacy of golimumab in methotrexate (MTX),naive patients with active rheumatoid arthritis (RA). Methods MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1). Results An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P = 0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P = 0.049) and between group 3 (40.5%; P = 0.038) but not group 4 (36.5%; P = 0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound ,5.2%; predefined delta value for noninferiority ,10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively. Conclusion Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns. [source] Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes1DIABETIC MEDICINE, Issue 5 2008T. Parkner Abstract Aims To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid-acting insulin analogue and once daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. Methods Twenty-one patients with Type 2 diabetes treated with oral glucose-lowering agents were randomized in this two-period crossover study to an equivalent 24-h dose of continuous subcutaneous infusion of insulin aspart and subsequently once-daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded. Results On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre-injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra-subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra-subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic-only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period. Conclusions Basal continuous subcutaneous infusion of a rapid-acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once-daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. [source] GAD65 autoantibody epitopes in adult patients with latent autoimmune diabetes following GAD65 vaccinationDIABETIC MEDICINE, Issue 5 2007L. M. Bekris Abstract Aims Subcutaneous injection of recombinant human GAD65 (rhGAD65) in patients with latent autoimmune diabetes in adults (LADA) correlates with an increase in C-peptide levels. In this study we analysed the effect of rhGAD65 administration on the GAD65-specific autoimmune response. Methods Longitudinal serum samples obtained from LADA patients (n = 47) who received 4, 20, 100 or 500 µg alum-formulated rhGAD65 or placebo by subcutaneous injection twice (4 weeks apart) were analysed for their epitope recognition using GAD65-specific recombinant Fab and GAD65/67 fusion proteins. Results Overall, minor changes in the epitope pattern were observed using either approach. Only in the 500-µg dosage group was an increase in GAD65Ab level associated with a significant increase in the binding to a conformational epitope located at the middle part of GAD65. Conclusions Our data suggest that the apparent beneficial effects of 20 µg alum-formulated recombinant human GAD65 is not explained by changes in the GAD65Ab epitope pattern. [source] No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucoseDIABETIC MEDICINE, Issue 2 2001T. Vilsbøll SUMMARY Aims It has previously been shown that intravenous and subcutaneous administration of glucagon-like peptide (GLP)-1 concomitant with intravenous glucose results in reactive hypoglycaemia in healthy subjects. Since GLP-1 is also effective in Type 2 diabetic patients and is presently being evaluated as a therapeutic agent in this disease, it is important to investigate whether GLP-1 can cause hypoglycaemia in such patients. Methods Eight Type 2 diabetic patients (age 54 (49,67) years; body mass index 31 (27,38) kg/m2; HbA1c 9.4 (7.0,12.5)%) and seven matched non-diabetic subjects (HbA1c 5.5 (5.2,5.8)%, fasting plasma glucose 5.4 (5.0,5.7) mmol/l) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body weight (maximally tolerated dose), and 15 min later, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. Results Hypoglycaemia with a PG at or below 2.5 mmol/l was seen in five of the seven healthy subjects after 60,70 min, but PG spontaneously increased again, reaching 3.7 (3.3,4.0) mmol/l at 90 min. In the patients, PG fell slowly and stabilized at 8.6 (4.2,12.1) mmol/l after 80 min. In both groups, glucagon levels initially decreased, but later increased, exceeding basal levels in healthy subjects, in spite of persistent, high concentrations of GLP-1 (P < 0.02). Conclusions Subcutaneous GLP-1 plus intravenous glucose induced reactive hypoglycaemia in healthy subjects, but not in Type 2 diabetic patients. Therefore, a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycaemia in Type 2 diabetes mellitus. [source] Augmentation of all- trans -retinoic acid concentration in plasma by preventing inflammation responses induced by atRA-loaded microspheres with concurrent treatment of dexamethasoneDRUG DEVELOPMENT RESEARCH, Issue 4 2004Kyeongsoon Park Abstract All- trans retinoic acid (atRA)-loaded microspheres severely induce inflammatory responses after microsphere implantation. Fibroblasts and a thick band of fibrous capsule resulting from the inflammatory responses could hamper drug permeation to the bloodstream because fibroblasts actively metabolize atRA into polar metabolites and the thick fibrous capsule acts as a diffusion barrier. In the present study, we investigated whether the fibroblast proliferation and collagen deposition induced by atRA released from microspheres might affect the atRA concentration in plasma and atRA metabolism with or without treatment of dexamethasone as an anti-inflammatory drug. After subcutaneous injection of atRA-loaded microspheres in rats, it was observed that atRA-loaded microspheres induced severe inflammatory responses and stimulated fibroblast proliferation and collagen deposition in fibrous capsules. On the other hand, the orally treated dexamethasone effectively prevented inflammatory responses in a dose-dependent manner and suppressed about 49% of the number of fibroblasts and collagen deposition in fibrous capsules at 14 days. In addition, after the treatment of dexamethasone, the atRA concentration in plasma was increased, and its metabolism was decreased approximately by 40% at 7 days, compared to the group treated alone with atRA-loaded microspheres. In conclusion, the concurrent treatment of dexmethasone with atRA-loaded microspheres could prevent inflammatory responses and metabolism of atRA, thereby maintaining the atRA concentration in plasma for longer periods in the therapeutic range. Drug Dev. Res. 61:197,206, 2004. © 2004 Wiley-Liss, Inc. [source] Modifying 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] Early Death Due to Severe Organophosphate Poisoning Is a Centrally Mediated ProcessACADEMIC EMERGENCY MEDICINE, Issue 4 2003Steven B. Bird MD Objective: To distinguish whether early death from severe organophosphate (OP) poisoning with dichlorvos is mediated through peripheral or central nervous system (CNS) actions. Methods: Wistar rats (n= 72) were randomized to pretreatment with either: normal saline (controls), peripheral anticholinergics (glycopyrrolate [low, medium, or high dose] or nebulized ipratropium bromide), or CNS + peripherally acting anticholinergics (diphenhydramine, nebulized atropine, or injected atropine). All treatments were given prior to a subcutaneous injection of 25 mg/kg dichlorvos (n= 8 per group). Survival was assessed at 10 minutes (early death) and 24 hours (delayed death). Kaplan-Meier (95% confidence intervals [95% CIs]) and chi-squared analysis was then performed to determine differences between treatments. Results: Regardless of treatment, all animals exhibited profound nicotinic effects (fasciculations) without obvious seizures within 2 minutes of poisoning. In rats pretreated with peripherally acting agents, the fasciculations were rapidly followed by reduced motor activity, sedation, and death. Mortality at 10 minutes for saline controls, glycopyrrolate, and ipratropium was 88%, 96%, and 100%, respectively. The single control animal surviving beyond 10 minutes went on to develop peripheral cholinergic manifestations, including hypersalivation, urination, and defecation. Only one of 24 animals treated with injected atropine, nebulized atropine, or diphenhydramine died during the early phase of poisoning; all others survived to 24 hours (p < 0.01). Conclusions: Death in acute, severe OP poisoning is prevented by pretreatment with anticholinergic agents that cross the blood,brain barrier, but not by agents with only peripheral actions. Early death due to OP poisoning appears to be a centrally mediated process. [source] Diphenhydramine as a Protective Agent in a Rat Model of Acute, Lethal Organophosphate PoisoningACADEMIC EMERGENCY MEDICINE, Issue 12 2002Steven B. Bird MD Objective: To evaluate the effects of diphenhydramine chloride (DPH) on mortality in a rat model of acute, severe organophosphate poisoning (OP).Methods: Wistar rats (n = 40) were randomized to pretreatment with either normal saline (controls), 5 mg/kg atropine, 3 mg/kg DPH, 15 mg/kg DPH, or 30 mg/kg DPH given as a single intramuscular injection 5 minutes prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). The primary endpoint was 10-minute survival. Survival at 24 hours was a secondary endpoint. Comparison of survival rates between groups was carried out by ANOVA and the Student-Newman-Keuls test. Results: Dichlorvos exposure resulted in profound fasciculations within 2 minutes of injection in all cohorts. In controls, fasciculations were followed by respiratory arrest within 10 minutes (0% survival). The rats receiving atropine pre-treatment exhibited similar fasciculations (nicotinic effects) without subsequent respiratory arrest, resulting in a significant improvement in survival (88%, p < 0.001). The DPH-treated rats exhibited a significant dose-dependent reduction in mortality, with the 3 mg/kg, 15 mg/kg, and 30 mg/kg groups demonstrating 0%, 25%, and 100% survival, respectively. There was no additional mortality between 10 minutes and 24 hours in any group. There was no significant difference in survival between the high-dose DPH and the atropine groups. Conclusions: Diphenhydramine chloride significantly reduced mortality in rats with acute, severe dichlorvos exposure. [source] Efficacy and safety of anti-D given by subcutaneous injection to patients with autoimmune thrombocytopeniaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2004Oliver Meyer No abstract is available for this article. [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] Induction of neuropeptides in skin innervating sensory neurons by stress and nerve growth factor as a possible reason for hair growth alterationEXPERIMENTAL DERMATOLOGY, Issue 9 2004A. Kuhlmei Recently, we introduced a mouse model launching experimental evidence for stress-induced hair growth inhibition (HGI), pointing to the existence of a brain-hair follicle axis (BFA). We suggested that nerve growth factor (NGF), besides neuropeptide substance P (SP), is a candidate mediator along the BFA. Published data further indicate that stress-related neuropeptides, e.g. calcitonin gene-related peptide (CGRP) and SP may be involved in HGI. SP and CGRP are synthesized in dorsal root ganglia (DRG) and released after axonal transport in the skin. Thus, aim of the present study was to investigate the effect of stress or subcutaneous injection of NGF, which mimics stress and regulates neuropeptide genes in sensory neurons, on the expression of SP and CGRP in DRG. Anagen was induced in C57BL/6 mice by depilation and retrograde tracing was employed on day 9 post-depilation (PD). On day 14 PD, mice were either exposed to sound stress (n = 4) injected subcutaneously with NGF (n = 4) or served as control (n = 4). On day 16 PD, DRG (mean of 30/mouse) were harvested and SP and CGRP in skin-specific sensory neurons, as identified by the tracer dye, were labelled by immunohistochemistry and counted. Stress exposure as well as NGF injection leads to a significant induction of SP and CGRP in retrograde-labelled neurons. This allows us to conclude that sensitive dermal nerve fibres are likely to originate from the presently identified neuropeptide-positive neurons. Peripheral activation of SP-expressing afferent nerve fibres via NGF-dependent pathways may cause neurogenic inflammation, eventually resulting in HGI. [source] Evidence for synaptic stripping by cortical microgliaGLIA, Issue 4 2007Bruce D. Trapp Abstract Recent studies have described significant demyelination and microglial activation in the cerebral cortex of brains from multiple sclerosis patients. To date, however, experimental models of cortical demyelination or cortical inflammation have not been extensively studied. In this report we describe focal cortical inflammation induced by stereotaxic injection of killed bacteria (BCG), followed 1 month later by subcutaneous injection of the same antigen, a protocol that overcomes the immune privilege of the cortex. Intracerebral BCG injection produced focal microglial activation at the injection site (termed acute lesion). Ten days after peripheral challenge (termed immune-mediated lesion), larger areas and higher densities of activated microglia were found near the injection site. In both paradigms, activated microglia and/or their processes closely apposed neuronal perikarya and apical dendrites. In the immune-mediated lesions, ,45% of the axosomatic synapses was displaced by activated microglia. Upon activation, therefore, cortical microglial migrate to and strip synapses from neuronal perikarya. Since neuronal pathology was not a feature of either the acute or immune-mediated lesion, synaptic stripping by activated microglia may have neuroprotective consequences. © 2006 Wiley-Liss, Inc. [source] Combination therapy with ribavirin and interferon in a cohort of children with hepatitis C and haemophilia followed at a pediatric haemophilia treatment centerHAEMOPHILIA, Issue 1 2004J. Puetz Summary., Nearly all children with bleeding disorders who received factor concentrates prior to the late 1980s were infected with hepatitis C. Treatment of adults infected with hepatitis C with combination therapy consisting of ribavirin and interferon has shown sustained response rates of 30,60%. Little data is available on the response of children infected with hepatitis C treated with combination therapy, especially those with bleeding disorders. We wish to report a single paediatric haemophilia treatment center's results of treatment of adolescents with haemophilia and hepatitis C infection with combination therapy. All patients followed at the haemophilia treatment center with hepatitis C, who were human immunodeficiency virus (HIV) negative and had a measurable hepatitis C viral load were eligible. Study patients received at least 6 months of 3 MU interferon- , via subcutaneous injection three times per week and 1000 mg day,1 of ribavirin. Eleven patients agreed to participate in the study. Three patients had an un measurable viral load after 6 months of combination therapy. All three completed 12 months of medication and continued to remain free of hepatitis C for 12 months after discontinuation of therapy. Side-effects of combination therapy were significant but tolerable. The sustained response rate in this study is similar to the historical response rate seen in adults but less than the other reported response rates seen in children treated with combination therapy. Given the toxicity of combination therapy, and natural history of hepatitis C infection in children, consideration of a liver biopsy to evaluate disease progression prior to considering antiviral medications is warranted. [source] Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in miceIMMUNOLOGY, Issue 2 2010Baojing Lu Summary Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine,phosphate,guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design. [source] Inflammatory cytokine production by immunological and foreign body multinucleated giant cellsIMMUNOLOGY, Issue 3 2000R. Hernandez-Pando Summary Multinucleated giant cells (MGC) are a common feature of granulomas. The mechanism of their formation has been studied extensively, but their function has not been completely characterized. A new method for the in vivo production of MGC was developed involving subcutaneous injection of microscopic nitrocellulose particles with adsorbed mycobacterial antigens into the footpads of sensitized BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non-sensitized mice (foreign body [FB]-MGC). The development of granulomas with a highly enriched MGC population was observed 2 weeks after the nitrocellulose injection. MGC were larger with a greater number of nuclei in I-MGC than in FB-MGC. From days 7,28 after nitrocellulose administration, the production of interleukin-1, (IL-1,) and tumour necrosis factor-, (TNF-,) was demonstrated in both MGC types by in situ reverse transcription,polymerase chain reaction (RT,PCR) and immunohistochemistry. After 2 months, the MGC had ceased production of IL-1, and TNF-,, but the expression of transforming growth factor-, (TGF-,) was very high, occurring together with extensive fibrosis. These results suggest that MGC are an active source of inflammatory cytokines, which can contribute to the initiation, maintenance and down-regulation of granulomatous inflammation induced by immunological and inert substances. [source] Phage display particles expressing tumor-specific antigens induce preventive and therapeutic anti-tumor immunity in murine p815 modelINTERNATIONAL JOURNAL OF CANCER, Issue 5 2002Yuzhang Wu Abstract The efficacy of phage display particles expressing tumor antigen P1A35-43 in inducing protective and therapeutic anti-tumor immune responses were studied. A protective immune response against a lethal progressive P815 mastocytoma tumor cell challenge was established after subcutaneous injection of phage display particles. Furthermore, the vaccine suppressed growth of pre-existing tumors. Immunization with the hybrid phage particles elicited P1A35,43 specific CTL responses and a Th1-dominated immune response with phage particle-specific secretion of IFN-, but not IL-4. Our results indicate that phage display particles might be a useful vaccine form for tumor-associated antigen epitopes in tumor immunotherapy. © 2002 Wiley-Liss, Inc. [source] Production of a new model of slowly progressive Heymann nephritisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2003Arpad Z. Barabas Summary., A slowly progressive autoimmune kidney disease was induced in Sprague Dawley rats by subcutaneous injection of a chemically modified kidney antigen (rKF3), incorporated into Alum and Distemper complex vaccine, followed by subcutaneous injections of an aqueous preparation of the same antigen. Pathogenic autoantibodies developed, which reacted with fixed glomerular nephritogenic antigen. Subsequently, immunopathological events lead to chronic progressive immune complex glomerulonephritis and proteinuria. The slowly developing disease was morphologically and functionally similar to Heymann nephritis (HN). The damage observed in the kidneys of experimental animals at 8 weeks and at the end of the experiment was examined by direct fluorescent antibody test, histology and electron microscopy. The changes were similar to the typical lesions found in HN rat kidneys, but less severe. Animals became proteinuric from 17 weeks onward (instead of the usual 4,8 weeks). By the end of the experiment, at 8 months, 100% of the rats were proteinuric. This new experimental model of autoimmune kidney disease, which is not complicated by intraperitoneal deposition and retention of Freund's complete adjuvant and renal tubular antigens, allowed us to investigate the pathogenesis of the disease processes from a different aspect, and promises to be a useful and improved model for the investigation of future treatment options. [source] Intracavitary administration of OK-432 with subcutaneous priming for malignant ascites in a case of advanced renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2002YUKIO KAGEYAMA Abstract The intracavitary injection of OK-432 (a streptococcal preparation) with subcutaneous priming has been shown to be an effective immunotherapy for patients with malignant effusion. We applied this treatment in a case of advanced renal cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by 10KE OK-432 intra-abdominal administration (day 9). The treatment was performed safely without major side-effects except for transient pyrexia. A significant reduction of ascites was noted 1 month after the treatment without subsequent re-accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems to be a simple, safe and effective treatment for ascites in advanced renal cell carcinoma. [source] Changes in adipocytes and dendritic cells in lymph node containing adipose depots during and after many weeks of mild inflammationJOURNAL OF ANATOMY, Issue 6 2005Dawn Sadler Abstract The time course and cellular basis for inflammation-induced hypertrophy of adipose tissue were investigated over 20 weeks in mature male rats. Mild inflammation was induced by subcutaneous injection of 20 µg lipopolysaccharide into one hind-leg three times/week for 4 or 8 weeks, followed by up to 12 weeks ,rest' without intervention. Mean volume and frequency of apoptosis (TUNEL assay) were measured in adipocytes isolated from sites defined by their anatomical relations to lymph nodes, plus numbers of CCL21-stimulated lymph node-derived and adipose tissue-derived dendritic cells. Experimental inflammation increased dendritic cells and adipocyte apoptosis in the locally stimulated popliteal depot and the lymphoid tissue-associated regions of the contralateral popliteal and mesentery and omentum. Responses declined slowly after inflammation ended, but all measurements from the locally stimulated popliteal depot, and the omentum, were still significantly different from controls after 12 weeks rest. The locally stimulated popliteal adipose tissue enlarged by 5% within 4 weeks and remained larger than the control. We conclude that prolonged inflammation induces permanent enlargement, greater adipocyte turnover and increased dendritic cell surveillance in the adjacent adipose tissue and the omentum. The experiment suggests a mechanism for selective hypertrophy of lymphoid tissue-associated adipose tissue in chronic stress and inflammatory disorders, including impaired lymph drainage, Crohn's disease and HIV-associated lipodystrophy, and a link between evolutionary fitness, sexual selection and aesthetically pleasing body symmetry. It would be useful for further study of molecular mechanisms in inflammation-induced local hypertrophy of adipose tissue and development of specific therapies that avoid interference with whole-body lipid metabolism. [source] Recovery of Trabecular and Cortical Bone Turnover After Discontinuation of Risedronate and Alendronate Therapy in Ovariectomized RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Robyn K Fuchs Abstract Alendronate (ALN) and risedronate (RIS) are bisphosphonates effective in reducing bone loss and fractures associated with postmenopausal osteoporosis. However, it is uncertain how long it takes bone turnover to be re-established after treatment withdrawal, and whether this differs between the two drugs. The objective of this study was to determine the time required to re-establish normal bone turnover after the discontinuation of ALN and RIS treatment in an animal model of estrogen-deficiency osteoporosis. Two hundred ten, 6-mo-old female Sprague-Dawley rats were ovariectomized and 6 wk later were randomized into baseline controls (n = 10) and four treatment groups (n = 50/group): vehicle-treated controls (CON; 0.3 ml sterile water), ALN (2.4 ,g/kg), low-dose RIS (RIS low; 1.2 ,g/kg), and high-dose RIS (RIS high; 2.4 ,g/kg). Treatments were administered 3 times/wk by subcutaneous injection. Baseline controls were killed at the initiation of treatment. Other groups were treated for 8 wk, and subgroups (n = 10/ treatment group) were killed 0, 4, 8, 12, and 16 wk after treatment was withdrawn. Static and dynamic histological analyses were performed for cortical (tibial diaphysis) and trabecular (proximal tibia and L4 vertebrae) bone. DXA and mechanical testing was performed on the L5 vertebra. After 8 wk of treatment, trabecular bone turnover rates were significantly suppressed in all drug-treated animals. Trabecular bone formation rate (BFR/BS) remained significantly lower than vehicle in bisphosphonate-treated animals through 12 wk. Sixteen weeks after treatment withdrawal, trabecular BFR/BS in the proximal tibia was re-established in animals treated with RIS but not in animals treated with ALN compared with controls. BMD of the fifth lumbar vertebra remained significantly higher than controls 16 wk after treatment withdrawal in ALN-treated animals but not in RIS-treated animals. Despite reductions in BMD and increases in bone turnover, ultimate force of the fifth lumbar vertebra remained significantly higher in all drug-treated animals through 16 wk after withdrawal. [source] The combined neuroprotective effects of lidocaine and dexmedetomidine after transient forebrain ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009T. GOYAGI Background: We investigated whether coadministration of lidocaine and dexmedetomidine would reduce brain injury following transient forebrain ischemia in rats to a greater extent than either drug alone. Methods: Adult male Sprague,Dawleyrats were anesthetized with halothane to maintain normocapnia and normoxia. Rats received subcutaneous injection of saline 1 ml/kg, lidocaine 10 mg/kg, dexmedetomidine 3 ,g/kg, or lidocaine 10 mg/kg plus dexmedetomidine 3 ,g/kg. Thirty minutes after the drug injection, forebrain ischemia was induced by hemorrhagic hypotension and occlusion of the bilateral carotid arteries, and was confirmed by isoelectric EEG. At the end of 10-min ischemia, rats were reperfused. The same dose of drugs was administered 3, 24, and 48 h after ischemia. Neurological examination was done at 1, 2, and 7 days after ischemia. Seven days after ischemia, the brain was stained with hematoxylin and eosin. We counted ischemic cells in the CA1 hippocampal region, striatum, and cerebral cortex. We also measured extracellular glutamate and norepinephrine concentration in hippocampal CA1 in the four groups. Results: As compared with saline-treated rats, rats receiving dexmedetomidine plus lidocaine showed less than neurological deficit scores at 2 and 7 days after ischemia, and had less ischemic cells in the CA1 region. However, administration of dexmedetomidine plus lidocaine did not alter the area under the glutamate concentration curve and norepinephrine concentration during ischemia in the CA1 region, compared with saline-treated rats. Conclusions: Our results suggest coadministration of lidocaine and dexmedetomidine improves the neurological outcome without alteration of glutamate and norepinephrine concentrations during forebrain ischemia in rats. [source] A Nonprostanoid EP4 Receptor Selective Prostaglandin E2 Agonist Restores Bone Mass and Strength in Aged, Ovariectomized RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2006Hua Zhu Ke MD Abstract CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 agonist. CP432 stimulates trabecular and cortical bone formation and restores bone mass and bone strength in aged ovariectomized rats with established osteopenia. Introduction: The purpose of this study was to determine whether a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 (PGE2) agonist, CP432, could produce bone anabolic effects in aged, ovariectomized (OVX) rats with established osteopenia. Materials and Methods: CP432 at 0.3, 1, or 3 mg/kg/day was given for 6 weeks by subcutaneous injection to 12-month-old rats that had been OVX for 8.5 months. The effects on bone mass, bone formation, bone resorption, and bone strength were determined. Results: Total femoral BMD increased significantly in OVX rats treated with CP432 at all doses. CP432 completely restored trabecular bone volume of the third lumbar vertebral body accompanied with a dose-dependent decrease in osteoclast number and osteoclast surface and a dose-dependent increase in mineralizing surface, mineral apposition rate, and bone formation rate-tissue reference in OVX rats. CP432 at 1 and 3 mg/kg/day significantly increased total tissue area, cortical bone area, and periosteal and endocortical bone formation in the tibial shafts compared with both sham and OVX controls. CP432 at all doses significantly and dose-dependently increased ultimate strength in the fifth lumber vertebral body compared with both sham and OVX controls. At 1 and 3 mg/kg/day, CP432 significantly increased maximal load in a three-point bending test of femoral shaft compared with both sham and OVX controls. Conclusions: CP432 completely restored trabecular and cortical bone mass and strength in established osteopenic, aged OVX rats by stimulating bone formation and inhibiting bone resorption on trabecular and cortical surfaces. [source] | ||||||||||||||||||||||||||||||||||||||||