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Local Administration (local + administration)
Selected AbstractsReview of Swedish regulation and monitoring of aquacultureJOURNAL OF APPLIED ICHTHYOLOGY, Issue 4-5 2000H. Ackefors Summary The aquaculture industry is governed by national Acts, ordinances and regulations. Provisions for the industry have been slightly modified since Sweden entered the EU in 1995. Swedish environmental legislation is applied when potential farmers ask for permission to cultivate. The Acts regulate farming sites, the discharge of water from farms and the species and strains that are permitted to be cultivated. The application procedure for fish farming is comprehensive and judged with regard to the Swedish Acts. Supervision of the aquaculture industry is performed by the County Administrative Board and sometimes also by the Local Administration. All farming units producing stocking material are strictly controlled in an elaborate scheme. Sweden has adopted European Community (EC) directives for shellfish, fish and water quality. Criteria for classifying water quality for concentrations of organic compounds and metals in blue mussels are worked out, and toxins in blue mussels are monitored. EC directives for fresh water quality which aim to sustain fish stocks are adopted as Swedish conditions. [source] Histamine H3 receptor-mediated impairment of contextual fear conditioning and in-vivo inhibition of cholinergic transmission in the rat basolateral amygdalaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001M. Beatrice Passani Abstract We investigated the effects of agents acting at histamine receptors on both, spontaneous release of ACh from the basolateral amygdala (BLA) of freely moving rats, and fear conditioning. Extensive evidence suggests that the effects of histamine on cognition might be explained by the modulation of cholinergic systems. Using the microdialysis technique in freely moving rats, we demonstrated that perfusion of the BLA with histaminergic compounds modulates the spontaneous release of ACh. The addition of 100 mm KCl to the perfusion medium strongly stimulated ACh release, whereas, 0.5 µm tetrodotoxin (TTX) inhibited spontaneous ACh release by more than 50%. Histaminergic H3 antagonists (ciproxifan, clobenpropit and thioperamide), directly administered to the BLA, decreased ACh spontaneous release, an effect fully antagonized by the simultaneous perfusion of the BLA with cimetidine, an H2 antagonist. Local administration of cimetidine alone increased ACh spontaneous release slightly, but significantly. Conversely, the administration of H1 antagonists failed to alter ACh spontaneous release. Rats receiving intra-BLA, bilateral injections of the H3 antagonists at doses similar to those inhibiting ACh spontaneous release, immediately after contextual fear conditioning, showed memory consolidation impairment of contextual fear conditioning. Post-training, bilateral injections of 50 µg scopolamine also had an adverse effect on memory retention. These observations provide the first evidence that histamine receptors are involved in the modulation of cholinergic tone in the amygdala and in the consolidation of fear conditioning. [source] Taurine selectively modulates the secretory activity of vasopressin neurons in conscious ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001Mario Engelmann Abstract Previous experiments have shown that a 10-min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 °C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABAA receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states. [source] Application of chitosan gel in the treatment of chronic periodontitisJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2007Hakan Ak Abstract Local administration of antibiotics in periodontal therapy can be provided with an appropriate delivery system. The purpose of this study was to evaluate the clinical effectiveness of chitosan, both as a carrier in gel form and as an active agent in the treatment of chronic periodontitis (CP). The chitosan gel (1% w/w) incorporated with or without 15% metronidazole was prepared and applied adjunctive to scaling and root planing (SRP) in comparison to SRP alone (control group-C), in CP patients. The clinical parameters such as probing depth (PD), clinical attachment level, the amount of gingival recession, plaque index, gingival index, and gingival bleeding time index were recorded at baseline and at weeks 6, 12, and 24. In all groups, significant improvements were observed in clinical parameters between baseline and week 24 (p < 0.05). The reductions in PD values were 1.21 mm for Ch, 1.48 mm for Ch + M, and 0.94 mm for C groups. No complications related to the chitosan were observed in patients throughout the study period. It is suggested that chitosan itself is effective as well as its combination with metronidazole in CP treatment due to its antimicrobial properties. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007 [source] Local administration of recombinant human antithrombin in a mouse model of peritoneal sepsisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2006S. LOUBELE [source] Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthmaALLERGY, Issue 1 2010A. Tomkinson Abstract Background:, Pitrakinra is a recombinant protein derived from human interleukin-4 (IL-4) that binds to IL-4R, and acts as a competitive antagonist of IL-4 and IL-13. The studies reported here compare the dose-ranging effects of pitrakinra on allergen-induced airway hyperresponsiveness (AHR) and airway eosinophilia when administered subcutaneously (s.c.) or by inhalation to the Ascaris suum -sensitive cynomolgus monkey for the purpose of elucidating the primary site of pitrakinra's anti-asthmatic action. Methods:, Airway responsiveness to inhaled methacholine and bronchoalveolar lavage cell composition was determined before and after three allergen exposures with a 1-week course of twice-daily (b.i.d.) s.c. or inhaled pitrakinra or placebo treatment. Results:, Treatment with s.c. pitrakinra significantly reduced allergen-induced AHR, with a maximum effect of a 2.8- to 3.8-fold increase in methacholine PC100 relative to control (P < 0.05) observed at b.i.d. s.c. doses of 0.05,0.5 mg/kg. Inhaled pitrakinra also significantly reduced AHR with a similar maximum effect of a 2.8- to 3.2-fold increase in methacholine PC100 relative to control (P < 0.05) at nominal b.i.d. doses of 3,100 mg. The maximal effect on AHR following inhalation was observed at a plasma concentration which exhibited no efficacy via the subcutaneous route. The effect of pitrakinra on lung eosinophilia was not statistically significant following either route of administration, although lung eosinophil count was reduced in all studies relative to control. Conclusion:, Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma. [source] Platelet activating factor (PAF) increases plasma protein extravasation and induces lowering of interstitial fluid pressure (Pif) in rat skinACTA PHYSIOLOGICA, Issue 1 2005V. V. Iversen Abstract Aim:, To investigate the ability of the microdialysis technique to measure capillary selectivity of different sized plasma proteins induced by local administration of platelet activating factor (PAF). Methods:, We used hollow plasmapheresis fibres with 3 cm membrane (cut off 3000 kDa) placed on the back of anaesthetized rats. Results:, Platelet activating factor (50 ,g mL,1) administered locally via the fibre, increased extravasation of radiolabelled 125I-HSA from plasma to the microdialysis fibre by approximately 900% compared both to baseline and the control fibre within 70 min (n = 6, P < 0.05). The extravasation in the control fibre did not change over time. HPLC measurement of plasma proteins in the microdialysis perfusate also demonstrated decreased capillary selectivity for proteins in the diameter range of 73 Å, 56 Å and 39 Å after local administration of PAF (n = 6, P < 0.05). PAF also significantly lowered interstitial fluid (Pif) pressure after subcutaneous administration (50 ,g mL,1). Mean arterial pressure (MAP) after intravenous injection of PAF (0.4 ,g kg,1) fell instantly by about 50 mmHg, and stabilized at 50 mmHg after 15 min (n = 6). MAP was unaltered when PAF was given through the microdialysis fibre (n = 4). Both total tissue water (TTW) and extravasation of albumin, measured as the plasma-to-tissue clearance (E-alb) showed a significant increase after PAF (n = 7, P < 0.05). Conclusions:, The present study demonstrates that PAF induces plasma protein extravasation and decrease capillary selectivity of different sized plasma proteins. It also increases transcapillary fluid flux, and lowers Pif, indicating a role for PAF in the interstitium for generation of transcapillary transport of water and large molecules followed by formation of oedema. [source] Imaging studies of biodistribution and kinetics in drug developmentDRUG DEVELOPMENT RESEARCH, Issue 2 2003Marc S. Berridge Abstract Although the intravenous route of administration is rarely used for drugs, it is by far the most common route for PET and SPECT radiotracers. This article discusses the use of planar and tomographic nuclear medicine technologies to image and quantify the distribution of drugs after local administration. In principle, this would include topical dermatologic, otic, ophthalmic, rectal, and vaginal administration, as well as the intramuscular, oral, and inhalation routes, although precedents do not yet exist for all of these. The studies reviewed focus mainly on oral ingestion and oral and nasal inhalation. The use of nondrug tracers for formulations is discussed, principally with planar imaging or SPECT using radionuclides such as 99mTc, as well as PET imaging where the active ingredient of a formulation can be labeled with 11C or sometimes 18F. An example of the latter type is a study of the deposition and kinetics in the lungs and airways of triamcinolone acetonide, an antiinflammatory steroid used for topical treatment of allergic rhinitis and asthma, dispensed from an inhaler. PET has high potential for evaluation of different formulations and delivery devices in the development of topically applied drugs. Drug Dev. Res. 59:208,226, 2003. © 2003 Wiley-Liss, Inc. [source] PRECLINICAL STUDY: Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbensADDICTION BIOLOGY, Issue 1 2007Elisabet Jerlhag ABSTRACT Ghrelin stimulates appetite, increases food intake and causes adiposity by mechanisms that include direct actions on the brain. Previously, we showed that intracerebroventricular administration of ghrelin has stimulatory and dopamine-enhancing properties. These effects of ghrelin are mediated via central nicotine receptors, suggesting that ghrelin can activate the acetylcholine,dopamine reward link. This reward link consists of cholinergic input from the laterodorsal tegmental area (LDTg) to the mesolimbic dopamine system that originates in the ventral tegmental area (VTA) and projects to the nucleus accumbens. Given that growth hormone secretagogue receptors (GHSR-1A) are expressed in the VTA and LDTg, brain areas involved in reward, the present series of experiments were undertaken to examine the hypothesis that these regions may mediate the stimulatory and dopamine-enhancing effects of ghrelin, by means of locomotor activity and in vivo microdialysis in freely moving mice. We found that local administration of ghrelin into the VTA (1 µg in 1 µl) induced an increase in locomotor activity and in the extracellular concentration of accumbal dopamine. In addition, local administration of ghrelin into the LDTg (1 µg in 1 µl) caused a locomotor stimulation and an increase in the extracellular levels of accumbal dopamine. Taken together, this indicates that ghrelin might, via activation of GHSR-1A in the VTA and LDTg, stimulate the acetylcholine,dopamine reward link, implicating that ghrelin is a part of the neurochemical overlap between the reward systems and those that regulate energy balance. [source] Rat strain differences in peripheral and central serotonin transporter protein expression and functionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Francesca Fernandez Abstract Female Fischer 344 (F344) rats have been shown to display increased serotonin transporter (5-HTT) gene expression in the dorsal raphe, compared to female Lewis (LEW) rats. Herein, we explored, by means of synaptosomal preparations and in vivo microdialysis, whether central, but also peripheral, 5-HTT protein expression/function differ between strains. Midbrain and hippocampal [3H]paroxetine binding at the 5-HTT and hippocampal [3H]serotonin (5-HT) reuptake were increased in male and female F344 rats, compared to their LEW counterparts, these strain differences being observed both in rats of commercial origin and in homebred rats. Moreover, in homebred rats, it was found that these strain differences extended to blood platelet 5-HTT protein expression and function. Saturation studies of midbrain and hippocampal [3H]paroxetine binding at the 5-HTT, and hippocampal and blood platelet [3H]5-HT reuptake, also revealed significant strain differences in Bmax and Vmax values. Although F344 and LEW rats differ in the activity of the hypothalamo-pituitary-adrenal (HPA) axis, manipulations of that axis revealed that the strain differences in hippocampal [3H]paroxetine binding at 5-HTTs and [3H]5-HT reuptake were not accounted for by corticosteroids. Hippocampal extracellular 5-HT levels were reduced in F344 rats, compared to LEW rats, with the relative, but not the absolute, increase in extracellular 5-HT elicited by the local administration of citalopram being larger in F344 rats. Because the aforementioned strain differences did not lie in the coding sequences of the 5-HTT gene, our results open the promising hypothesis that F344 and LEW strains model functional polymorphisms in the promoter region of the human 5-HTT gene. [source] Stimulation of intramembranous bone repair in rats by ghrelinEXPERIMENTAL PHYSIOLOGY, Issue 7 2008Feilong Deng Researchers in our laboratory have previously shown that ghrelin, a gastric peptide hormone, may regulate mesenchymal cell differentiation into adipocytes and myocytes. Here we show that ghrelin promotes osteogenesis of intramembranous bone and improves the repair of calvarial bone defects in rats. Rats with a 9 mm full-thickness calvarial bone defect received either Bio-Oss® (control group) or Bio-Oss® mixed with 20 ,g ghrelin (treatment group), followed by local administration of saline or ghrelin (10 ,g), respectively, on days 5, 10 and 15. After 6 and 12 weeks, new bone formation was assessed. Animals treated with ghrelin showed a significant increase in new bone formation as demonstrated by an increment in bone mineral density and fluorescence labelling of tetracycline relative to the control group. At 6 weeks, bone mineral density increased from 54 ± 7 (control group) to 78 ± 9 mg cm,2 in the treatment group, while the tetracycline fluorescence labelling increased by 61 ± 15%. A similar increment was observed at 12 weeks. Quantitative reverse transcriptase-polymerase chain reaction showed that expression of alkaline phosphatase (ALP), osteocalcin and collagen type I was elevated. Relative to the control animals, mRNAs for ALP, osteocalcin and collagen type I increased 2.4 ± 0.4-, 4.7 ± 1.9- and 4.0 ± 1.7-fold, respectively, in animals treated with ghrelin for 6 weeks (P < 0.05). At 12 weeks, mRNA levels of ALP, osteocalcin and collagen type I showed a decline relative to levels at 6 weeks but still remained significantly higher than in the control group, with fold changes of 2.4 ± 0.8, 2.4 ± 1.2 and 2.1 ± 0.7, respectively (P < 0.05). This study demonstrated that ghrelin stimulates intramembranous osteogenesis. [source] Central State Power and its Limits in Bulpitt's Territory and PowerGOVERNMENT AND OPPOSITION, Issue 3 2010Peter John This article assesses Bulpitt's treatment of the centre or central state. It begins by reviewing Bulpitt's argument that the UK centre elite developed a detached style of territorial management and recognized the limits to the state's power. The argument is that the elite at the centre sought to avoid the costs of intervention in the periphery so it could retain its autonomy over decisions affecting the economy and international affairs. The article then assesses Bulpitt's claims against extant evidence from the study of UK politics. It concludes that, in spite of Bulpitt's failure to appreciate the interest of the centre in the detail of local administration, the account holds up surprisingly well and could be adopted as a comparative framework for analysing how central elites seek to keep their grip on power by managing territorial politics successfully. [source] Paradoxical Vasodilation During Lower Body Negative Pressure in Patients with Vasodepressor Carotid Sinus SyndromeJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2003Arduino A. Mangoni MD OBJECTIVES: To elucidate the pathophysiological mechanism of the vasodepressor form (VD) of carotid sinus syndrome (CSS) by maneuvers designed to induce generalized sympathetic activation after baroreceptor unloading (lower body negative pressure, LBNP) or direct peripheral adrenoreceptor stimulation via local administration of norepinephrine (NA). DESIGN: Subjects were identified with VD of CSS through diagnostic testing. SETTING: Research laboratory. PARTICIPANTS: Eleven young controls (YC) (mean age ± standard error of mean = 22.8 ± 0.7), eight elderly controls (EC) (72.6 ± 0.6), and eight elderly patients with VD (78.7 ± 1.7). MEASUREMENTS: Forearm arterial blood flow (FABF) was measured in the left and right arms by venous occlusion plethysmography. Measurements were performed during baseline conditions, LBNP (,20 mmHg), and intra-arterial NA infusion in the left brachial artery at three progressively increasing rates (60, 120, and 240 pmol/min). RESULTS: During LBNP, FABF significantly decreased in YC (baseline 3.61 ± 0.30 vs ,20 mmHg 2.96 ± 0.24 mL/100 g/min, P = .030) and EC (4.05 ± 0.74 vs 3.69 ± 0.65 mL/100 g/min, P = .033) but increased in elderly patients with VD (3.65 ± 0.60 vs 4.54 ± 0.80 mL/100 g/min, P = .020). During NA infusion, a significant forearm vasoconstriction occurred in YC (FABF left:right ratio 1.00 ± 0.05 at baseline; 0.81 ± 0.08 at 60 pmol/min, P = .034; 0.81 ± 0.05 at 120 pmol/min, P < .001; 0.72 ± 0.04 at 240 pmol/min, P < .001), whereas no significant FABF changes were observed in EC (1.04 ± 0.06; 0.96 ± 0.07, P = .655; 0.89 ± 0.10, P = .401; 0.94 ± 0.10, P = .590) or elderly patients with VD (1.04 ± 0.06; 1.16 ±0 .10, P = .117; 1.04 ± 0.08, P = .602; 1.11 ± 0.10, P = .305). CONCLUSION: VD of CSS is associated with a paradoxical vasodilatation during LBNP and an impairment of peripheral ,-adrenergic responsiveness, which may be age-related. [source] Retention, Distribution, and Effects of Intraosseously Administered Ibandronate in the Infarcted Femoral Head,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007James Aya-ay Abstract The local distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted femoral heads were studied. Intraosseous administration effectively delivered and distributed ibandronate in the infarcted femoral heads and decreased the femoral head deformity in a large animal model of Legg-Calve-Perthes disease. Introduction: Bisphosphonate therapy has gained significant attention for the treatment of ischemic osteonecrosis of the femoral head (IOFH) because of its ability to inhibit osteoclastic bone resorption, which has been shown to contribute to the pathogenesis of femoral head deformity. Because IOFH is a localized condition, there is a need to explore the therapeutic potential of local, intraosseous administration of bisphosphonate to prevent the femoral head deformity. The purpose of this study was to investigate the distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted head. Materials and Methods: IOFH was surgically induced in the right femoral head of 27 piglets. One week later, a second operation was performed to inject 14C-labeled or unlabeled ibandronate directly into the infarcted head. 14C-ibandronate injected heads were assessed after 48 h, 3 weeks, or 7 weeks later to determine the distribution and retention of the drug using autoradiography and liquid scintillation analysis. Femoral heads injected with unlabeled ibandronate were assessed at 7 weeks to determine the degree of deformity using radiography and histomorphometry. Results: Autoradiography showed that 14C-Ibandronate was widely distributed in three of the four heads examined at 48 h after the injection. Liquid scintillation analysis showed that most of the drug was retained in the injected head, and almost negligible amount of radioactivity was present in the bone and organs elsewhere at 48 h. At 3 and 7 weeks, 50% and 30% of the 14C-drug were found to be retained in the infarcted heads, respectively. Radiographic and histomorphometric assessments showed significantly better preservation of the infarcted heads treated with intraosseous administration of ibandronate compared with saline (p < 0.001). Conclusions: This study provides for the first time the evidence that local intraosseous administration is an effective route to deliver and distribute ibandronate in the infarcted femoral head to preserve the femoral head structure after ischemic osteonecrosis. In a localized ischemic condition such as IOFH, local administration of bisphosphonate may be preferable to oral or systemic administration because it minimizes the distribution of the drug to the rest of the skeleton and bypasses the need for having a restored blood flow to the infarcted head for the delivery of the drug. [source] Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2010Petrica-Adrian Panaite Abstract Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine ,-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission. © 2010 Wiley-Liss, Inc. [source] Role of systemic and local administration of selective inhibitors of cyclo-oxygenase 1 and 2 in an experimental model of periodontal disease in ratsJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2009C. M. Queiroz-Junior Background and Objective:, Periodontal disease is an inflammatory condition of tooth-supporting tissues. Arachidonic acid metabolites have been implicated in development of periodontal disease, especially those derived from the cyclo-oxygenase (COX) pathway. This study investigated the role of inhibitors of cyclo-oxygenases (COX-1 and COX-2) in a model of periodontal disease in rats. Material and Methods:, A ligature was placed around the molar of rats. Losses of fiber attachment and of alveolar bone were measured morphometrically in histologically prepared sections. Infiltration of cells into gingival tissue surrounding the ligated tooth was also determined. Results:, Systemic and local administration of non-selective and selective COX-2 inhibitors, preventively, resulted in significant reduction of the losses of fiber attachment and alveolar bone, as well as decreased leukocyte numbers in gingival tissue. Preventive selective inhibition of COX-1 was as effective as COX-2 inhibition in reducing local fiber attachment loss and cell migration, but did not prevent alveolar bone loss. Conclusion:, Our results provide evidence for participation of COX-1 and COX-2 in early stages of periodontal disease in rats. Furthermore, local administration of COX inhibitors reduced the signs of periodontal disease to the same extent as systemic treatment. Therapeutic approaches incorporating locally delivered anti-inflammatory drugs could be of benefit for patients suffering from periodontal disease. [source] Microparticulate formulations for the controlled release of interleukin-2JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2004Tommy T. Thomas Abstract Interleukin 2 (IL-2) is a pleotropic growth factor essential to immune system function. Current methods of administration are limited by the necessity of hospitalization as well as dose-limiting toxicities and side effects. There is also the issue of low therapeutic concentrations at the desired site of action; for instance, in the case of solid tumor treatment. Here we describe the design of controlled-release vehicles for the local administration of IL-2 based on single (SE) and double emulsion (DE) poly(lactic- co -glycolic acid) (PLGA) systems and a newly developed class of spray-dried lipid,protein,sugar systems composed of L -,-dipalmitoylphosphatidylcholine (DPPC) and 0.2% Eudragit E 100. All three systems demonstrated the release of therapeutic drug quantities. Totals of 2.0, 0.5, and 2.8 ,g of IL-2 (per mg of solid) were encapsulated in the SE, DE, and spray-dried formulations, respectively. The SE and DE released of 30 and 15% of the encapsulated protein, respectively, with delivery of biologically active IL-2 during the first 5 to 10 days. The lipid,protein,sugar-based system demonstrated extended sustained release of biologically active IL-2 for a period of 4 months. These systems provide a potential framework for long-term loco-regional immunotherapeutic treatment regimens. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1100,1109, 2004 [source] Regulating hospital use: length of stay, beds and whiteboardsNURSING INQUIRY, Issue 1 2005Marie Heartfield This paper presents part of a larger study of contemporary nursing practice and the rationalisation of hospital length of stay. Informed by Michel Foucault's work on governmentality, length of hospital stay and the re-engineering of surgical services are examined, not in terms of numerical representations of hospital use, but as part of social and political processes through which certain concepts are made susceptible to measurement and practices are organised. Using data generated through fieldwork in a hospital surgical division this analysis offers understandings of how social practices around length of hospital stay are translated and how they pattern contemporary hospital nursing practice. Nursing practice is explored through the reconstitution of hospital beds and the demands of local administration of hospital length of stay. [source] OC8 The short-term efficacy of osseointegrated implants in patients with non-malignant oral mucosal disease: a case seriesORAL DISEASES, Issue 2006TA Hodgson Purpose, The spectrum of patients who may wish or warrant osseointegrated implants is increasing, despite few reports of the impact of non-malignant oral mucosal disease upon implant placement. This report details the implant placement outcomes in three patients with pre-existing oral mucosal disease. Case reports,A: Four implants were placed in the lower anterior region of a 78-year-old female with longstanding mucous membrane pemphigoid (MMP) in 2004. The MMP had resulted in extensive cicatrisation of the upper and lower buccal and labial vestibules. One implant failed to osseointegrate, but was successfully replaced. There have been no other postplacement adverse events, despite the MMP remaining mildly active. B: A 36-years-old male with orofacial granulomatosis characterised by recurrent lip swelling and gingival enlargement, had a single implant placed in the upper canine region in 2001. Although still in situ significant peri-implant alveolar bone loss has occurred and has been stabilised by repeated debridement, local administration of topical minocycline and several courses of systemic metronidazole. C: A 53-years-old female with oral manifestations of diffuse systemic sclerosis and fibrosing alveolitis had four lower anterior mandibular implants placed in 1995 to support an 8 unit bridge. One episode of peri-implant inflammation was controlled with local debridement and topical chlorhexidine mouthrinse. The implants remain satisfactory 11 years postinsertion. Conclusion, The short-term failure of osseointegrated implant integration appears uncommon in patients with non-malignant oral mucosal disease. There remains a need to establish appropriate case selection criteria and monitor outcomes. [source] Black cumin seed essential oil, as a potent analgesic and antiin,ammatory drugPHYTOTHERAPY RESEARCH, Issue 3 2004Valiollah Hajhashemi Abstract The steam-distilled essential oil of Iranian black cumin seed (Nigella sativa L.) was investigated for its composition and analgesic and antiin,ammatory properties. After oil analysis by GC/MS, 20 compounds were identi,ed in the oil, obtained in 0.4% (v/w) yield. Among them, para -cymene (37.3%) and thymoquinone (13.7%) were the major components. Acetic acid-induced writhing, formalin and light tail ,ick tests were used for assessment of analgesic activity. Antiin,ammatory activity was evaluated using carrageenan-induced paw oedema in rats and croton oil-induced ear oedema in mice. Black cumin seed essential oil (BCSEO) was found to produce a signi,cant analgesic effect in acetic acid-induced writhing, formalin and light tail ,ick tests. Naloxone, an opioid antagonist, could not reverse the analgesic effect observed in the formalin test. Although oral administration of BCSEO at doses of 100, 200 and 400 µL/kg did not exert a signi,cant antiin,ammatory effect in the carrageenan test, i.p. injection of the same doses signi,cantly (p < 0.001) inhibited carrageenan-induced paw oedema. BCSEO at doses of 10 and 20 µL/ear could also reduce croton oil-induced oedema. It seems that mechanism(s) other than opioid receptors is (are) involved in the analgesic effect of BCSEO since naloxone could not reverse this effect. Both systemic and local administration of BCSEO showed antiin,ammatory activity. Thymoquinone, as one of the major components of BCSEO, probably has an important role in these pharmacological effects. Copyright © 2004 John Wiley & Sons, Ltd. [source] Development and characterization of a synthetic promoter for selective expression in proliferating endothelial cellsTHE JOURNAL OF GENE MEDICINE, Issue 4 2006P. Szymanski Abstract Background Systemic administration of non-viral gene therapy provides better access to tumors than local administration. Development of a promoter that restricts expression of cytotoxic proteins to the tumor vasculature will increase the safety of the system by minimizing expression in the non-dividing endothelial cells of the vasculature of non-target tissues. Methods Cell cycle promoters were tested for selective expression in dividing cells vs. non-dividing cells in vitro and promoter strength was compared to the cytomegalovirus (CMV) promoter. Successful promoter candidates were tested in vivo using two proliferating endothelium mouse models. Ovarectomized mice were injected with estradiol prior to lipoplex administration and expression levels were measured in the lungs and uterus 4 days after administration. The second model was a subcutaneous tumor model and expression levels were measured in the lungs and tumors. For both animal models, expression levels from the proliferating endothelium promoter were compared to that obtained from a CMV promoter. Results The results showed that the Cdc6 promoter yielded higher expression in proliferating vs. non-proliferating cells. Secondly, promoter strength could be selectively increased in endothelial cells by the addition of a multimerized endothelin enhancer (ET) to the Cdc6 promoter. Thirdly, comparison of expression levels in the lungs vs. uterus in the ovarectomized mouse model and lungs vs. tumor in the mouse tumor model showed expression was much higher in the uterus and the tumor than in the lungs for the ET/Cdc6 promoter, and expression levels were comparable to that of the CMV promoter in the hypervascularized tissues. Conclusions These results demonstrate that the combination of the endothelin enhancer with the Cdc6 promoter yields selective expression in proliferating endothelium and can be used to express cytotoxic proteins to treat vascularized tumors. Copyright © 2006 John Wiley & Sons, Ltd. [source] Oncolytic virotherapy for cancer treatment: challenges and solutionsTHE JOURNAL OF GENE MEDICINE, Issue 11 2005J. J. Davis Abstract Advances in gene modification and viral therapy have led to the development of a variety of vectors in several viral families that are capable of replication specifically in tumor cells. Because of the nature of viral delivery, infection, and replication, this technology, oncolytic virotherapy, may prove valuable for treating cancer patients, especially those with inoperable tumors. Current limitations exist, however, for oncolytic virotherapy. They include the body's B and T cell responses, innate inflammatory reactions, host range, safety risks involved in using modified viruses as treatments, and the requirement that most currently available oncolytic viruses require local administration. Another important constraint is that genetically enhanced vectors may or may not adhere to their replication restrictions in long-term applications. Several solutions and strategies already exist, however, to minimize or circumvent many of these limitations, supporting viral oncolytic therapy as a viable option and powerful tool in the fight against cancer. Copyright © 2005 John Wiley & Sons, Ltd. [source] Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivativesTHE JOURNAL OF GENE MEDICINE, Issue 8 2005Michael Neu Abstract The continually increasing wealth of knowledge about the role of genes involved in acquired or hereditary diseases renders the delivery of regulatory genes or nucleic acids into affected cells a potentially promising strategy. Apart from viral vectors, non-viral gene delivery systems have recently received increasing interest, due to safety concerns associated with insertional mutagenesis of retro-viral vectors. Especially cationic polymers may be particularly attractive for the delivery of nucleic acids, since they allow a vast synthetic modification of their structure enabling the investigation of structure-function relationships. Successful clinical application of synthetic polycations for gene delivery will depend primarily on three factors, namely (1) an enhancement of the transfection efficiency, (2) a reduction in toxicity and (3) an ability of the vectors to overcome numerous biological barriers after systemic or local administration. Among the polycations presently used for gene delivery, poly(ethylene imine), PEI, takes a prominent position, due to its potential for endosomal escape. PEI as well as derivatives of PEI currently under investigation for DNA and RNA delivery will be discussed. This review focuses on structure-function relationships and the physicochemical aspects of polyplexes which influence basic characteristics, such as complex formation, stability or in vitro cytotoxicity, to provide a basis for their application under in vivo conditions. Rational design of optimized polycations is an objective for further research and may provide the basis for a successful cationic polymer-based gene delivery system in the future. Copyright © 2005 John Wiley & Sons, Ltd. [source] Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanismsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2002C. G. Crandall The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through ,-adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser-Doppler flowmetry over sites following local administration of terazosin (,1 -antagonist), yohimbine (,2 -antagonist), phentolamine (non-selective ,-antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 ± 1 cm below the heart. The arm remained in this position for 2 min. Selective and non-selective ,-adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering ,-adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non-adrenergic, but neurally mediated, local mechanism. [source] Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx,THE LARYNGOSCOPE, Issue 7 2008Stacey L. Halum MD Abstract Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation-induced muscle atrophy and provide a vehicle for delivery of neurotrophic factors, thereby potentially selectively guiding reinnervation. The goal of this project was to characterize optimal conditions for injected autologous MSC survival in the thyroarytenoid (TA) muscle following recurrent laryngeal nerve (RLN) injury by local administration of adjuvant factors. Study Design: Animal experiment. Methods: Unilateral RLN transection and sternocleidomastoid muscle (,1 g) biopsies were performed in 20 male Wistar rats. One month later, 106 autologous MSCs labeled via retroviral-enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10,5 M], insulin-like growth factor-1 [(IGF- 1) 100 ,g/mL], ciliary neurotrophic factor [(CNTF) 50 ,g/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival. Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF-1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival. Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF-1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion. [source] Calotropis procera latex-induced inflammatory hyperalgesia , effect of bradyzide and morphineAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2007Vijay L. Kumar Summary 1,The milky white latex of the plant Calotropis procera induces inflammatory response upon accidental exposure and on local administration that could be effectively ameliorated by antihistaminic and standard anti-inflammatory drugs. 2,The aim of the present study was to evaluate the anti-oedematogenic and analgesic effect of the bradykinin antagonist, bradyzide (BDZ) and the opioidergic analgesic, morphine (Mor) against inflammatory hyperalgesia induced by the dried latex (DL) of C. procera in the rat paw oedema model. 3,An aqueous solution of DL (0.1 ml of 1% solution) was injected into the sub-plantar surface of the rat paw and the paw volume was measured at different time intervals. The inhibitory effect of bradyzide and morphine on oedema formation and hyperalgesic response was compared with that of cyproheptadine (CPH), a potent inhibitor of DL-induced oedema formation. 4,The hyperalgesic response was evaluated by the dorsal flexion pain test, compression test and by observing motility, stair-climbing ability, and the grooming behaviour of the rats. 5,The effect of these drugs was also evaluated against DL-induced writhings in the mouse model. 6,Both bradyzide and morphine inhibited DL-induced oedema formation by 30,40% and CPH was more effective in this regard (81% inhibition). The antihyperalgesic effect of both the drugs was more pronounced than that of CPH. Both bradyzide and morphine markedly inhibited the grooming behaviour and the effect of morphine could be reversed by pretreatment with naloxone. 7,Thus, our study shows that DL-induced oedema formation is effectively inhibited by antihistaminic/antiserotonergic drug and associated hyperalgesia by analgesic drugs. [source] Reversal of acid-induced and inflammatory pain by the selective ASIC3 inhibitor, APETx2BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010Jerzy Karczewski BACKGROUND AND PURPOSE Inflammatory pain is triggered by activation of pathways leading to the release of mediators such as bradykinin, prostaglandins, interleukins, ATP, growth factors and protons that sensitize peripheral nociceptors. The activation of acid-sensitive ion channels (ASICs) may have particular relevance in the development and maintenance of inflammatory pain. ASIC3 is of particular interest due to its restricted tissue distribution in the nociceptive primary afferent fibres and its high sensitivity to protons. EXPERIMENTAL APPROACH To examine the contribution of ASIC3 to the development and maintenance of muscle pain and inflammatory pain, we studied the in vivo efficacy of a selective ASIC3 inhibitor, APETx2, in rats. KEY RESULTS Administration of APETx2 into the gastrocnemius muscle prior to the administration of low pH saline prevented the development of mechanical hypersensitivity, whereas APETx2 administration following low-pH saline was ineffective in reversing hypersensitivity. The prevention of mechanical hypersensitivity produced by acid administration was observed whether APETx2 was applied via i.m. or i.t. routes. In the complete Freund's adjuvant (CFA) inflammatory pain model, local administration of APETx2 resulted in a potent and complete reversal of established mechanical hypersensitivity, whereas i.t. application of APETx2 was ineffective. CONCLUSIONS AND IMPLICATIONS ASIC3 contributed to the development of mechanical hypersensitivity in the acid-induced muscle pain model, whereas ASIC3 contributed to the maintenance of mechanical hypersensitivity in the CFA inflammatory pain model. The contribution of ASIC3 to established hypersensitivity associated with inflammation suggests that this channel may be an effective analgesic target for inflammatory pain states. [source] Effects of local delivery of trapidil on neointima formation in a rabbit angioplasty modelBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2000Kai Zacharowski Smooth muscle cell (SMC) proliferation can result in luminal reduction of a vessel following balloon angioplasty. This study was designed (i) to determine if local administration of trapidil (triazolopyrimidine) into a vessel wall reduces neointima formation, and (ii) to explore the mechanism involved in the subsequent reduction in cell proliferation. Following balloon angioplasty in 40 anaesthetized New Zealand White rabbits, trapidil (50,200 mg) or its vehicle (saline) was injected into the dilated vessel wall of the right femoral artery. Experimental groups and time of investigation: (I) vehicle (2 weeks, n=3), (II) trapidil-100 mg (2 weeks, n=3), (III) vehicle (3 weeks, n=8), (IV) trapidil-50 mg (3 weeks, n=5); (V) trapidil-100 mg (3 weeks, n=9) or (V) trapidil-200 mg (3 weeks, n=7). After 2 weeks, there was a significant reduction of intimal hyperplasia (expressed as intima to media area ratio) in the trapidil group compared with vehicle (0.44±0.04 vs 0.93±0.04, *P<0.05) and also a significant reduction in cell proliferation (% ratio of BrdU-positive cells to total cell number: vehicle 14±2% vs trapidil 6±1%, *P<0.05). After 3 weeks, there was a dose-dependent reduction of intimal hyperplasia in the trapidil groups compared with vehicle (trapidil 50 mg 1.14±0.04; trapidil 100 mg 0.91±0.09*; trapidil 200 mg 0.77±0.09* vs vehicle 1.67±0.23, *P<0.05). Thus, the local administration of trapidil to the rabbit femoral artery reduces the neointima formation, which occurs 2 or 3 weeks after balloon angioplasty via a mechanism, which is dependent on inhibition of cell proliferation. British Journal of Pharmacology (2000) 129, 566,572; doi:10.1038/sj.bjp.0703098 [source] Progressive labour policy, ageing Marxism and unrepentant early capitalism in the Chinese industrial revolutionBUSINESS ETHICS: A EUROPEAN REVIEW, Issue 2 2001Orlan Lee The institutional guarantees of modern labour law, that provide the keystone of progressive liberalism, are often only reactionary to the entrenched concepts of socialist law. Adoption of institutions of "workers rights", and employment protection based upon contract, inevitably nullify the ideological promise of the inalienable "right to work". China, among the last bastions of theoretical Marxist socialism, and among the first socialist countries ready to accept that it has been in desperate need of reforming uneconomical state enterprises, seems willing to sacrifice ideological purity for economic development. Yet, if economic turnaround requires enterprise rationalisation in a market economy, it is understandable that Chinese labour requires the same kinds of protection against unbridled capitalism as progressive labour movements elsewhere. Doubtless, for those who have enjoyed no such institutional guarantees in the past, official commitment to improvement of labour conditions is better than no acknowledgment of need for reform of social policy whatever. Yet, the real question for students of social change is "Are these legislated reforms effective policy guides for local administration and the courts?""|Or are they merely regulations for licensing compliance , primarily for foreign invested enterprises?". In brief, "... to what extent are the new ,workers' rights' realistically attainable sources of judicial remedies for individual workers?" [source] Enduring, ephemeral and emerging issues in public administration in Canada: Trends in Canadian Public Administration over fifty years (1958,2007)CANADIAN PUBLIC ADMINISTRATION/ADMINISTRATION PUBLIQUE DU CANADA, Issue 4 2007Barbara Wake Carroll It is the 50th anniversary issue of the Journal, and it is the last issue to be published by the Institute of Public Administration of Canada. For this issue, we have not produced a "special issue" in the sense of commissioning particular articles. Instead, we have brought together a number of articles that were already in the "pipeline" but that the editors thought made a particular contribution to public administration in Canada. This introductory article, or editor's review, is a retrospective analysis of the content of the Journal. It would appear that while there has been a slight shift towards public policy and a greater concern with provincial and local administration, cpa has maintained an enduring interest in its core areas of administrative theory and political and legal institutions. The content is also compared with findings of the content of other journals and also other analyses of cpa. This review is followed by commentaries by former editors and associate editors on their experiences with the Journal. [source] | ||||||||||||||||||||||||||||||||||