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Sample records for intradermally injected syngeneic

  1. [Anaphylactic shock after intradermal injection of corticosteroid].

    PubMed

    Meyer, Martin Willy; Zachariae, Claus; Garvey, Lene Heise

    2015-01-19

    Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food products, pharmaceuticals and cosmetics. Allergy to CMC in parenteral corticosteroid preparations leading to anaphylaxis is rare, but has previously been reported. We report a case of a 52-year-old woman with prurigo nodularis of Hyde, who reacted with anaphylaxis after intradermal injection of Kenalog 40 mg/ml. Allergy testing showed a positive skin prick test for CMC and the patient was advised to avoid future parenteral exposure to CMC. This case highlights the need to examine excipients in severe cases of drug allergy.

  2. Contralateral hyperalgesia and allodynia following intradermal capsaicin injection in man

    PubMed Central

    Haigh, R. C.; Mapp, P. I.; Harris, N.; Blake, D. R.

    2008-01-01

    Objectives. Contralateral responses to unilateral stimuli have been well described in animal models. These range from central sensitization to peripheral inflammatory responses. Our aim was to test for contralateral responses following unilateral intradermal capsaicin injection in man. Methods. Three groups were investigated. A healthy volunteer group (1) was injected with capsaicin into the volar aspect of one forearm. A group of patients with RA (2) was also injected with capsaicin. A control group of healthy volunteers (3) was not injected with capsaicin. All groups were tested for hyperalgesia and allodynia every 10 min for 1 h following the injection using quantitative sensory testing. Results. A total of 9/14 healthy volunteers (Group 1) and 10/14 patients with RA (Group 2) demonstrated contralateral sensitization that subsided within 1 h following intradermal capsaicin injection. A total of 2/23 control subjects (Group 3) demonstrated positive responses with the monofilaments. The frequency of the contralateral responses in the experimental groups compared with the control group is significant (P < 0.05). The peak hyperalgesia was relatively delayed contralaterally compared with the ipsilateral side (35 min vs 15 min). The area of sensitization, where present, was reduced compared with the ipsilateral side (5–50%). Conclusions. This is the first demonstration of a contralateral response following a unilateral stimulus in man. Bilateral neural pathways mediating contralateral responses may have a role in the pathophysiology of chronically painful or inflammatory diseases and a confounding influence on using the contralateral limb as a control experimentally. We did not find that a systemic inflammatory disease sensitized for this phenomenon. PMID:18632788

  3. Profound Hypotension after an Intradermal Injection of Indigo Carmine for Sentinel Node Mapping

    PubMed Central

    Jo, Youn Yi; Lee, Mi Geum; Yun, Soon Young

    2013-01-01

    Intradermal injections of indigo carmine for sentinel node mapping are considered safe and no report of an adverse reaction has been published. The authors described two cases of profound hypotension in women that underwent breast-conserving surgery after an intradermal injection of indigo carmine into the periareolar area for sentinel node mapping. PMID:23593094

  4. Profound hypotension after an intradermal injection of indigo carmine for sentinel node mapping.

    PubMed

    Jo, Youn Yi; Lee, Mi Geum; Yun, Soon Young; Lee, Kyung Cheon

    2013-03-01

    Intradermal injections of indigo carmine for sentinel node mapping are considered safe and no report of an adverse reaction has been published. The authors described two cases of profound hypotension in women that underwent breast-conserving surgery after an intradermal injection of indigo carmine into the periareolar area for sentinel node mapping.

  5. Severe acute caffeine poisoning due to intradermal injections: mesotherapy hazard.

    PubMed

    Vukcević, Natasa Perković; Babić, Gordana; Segrt, Zoran; Ercegović, Gordana Vuković; Janković, Snezana; Aćimović, Ljubomir

    2012-08-01

    Caffeine is indicated in the treatment of migraine headaches, as well as neonatal apnea and bradycardia syndrome. In mild poisoning, the most prevalent symptoms are nausea, vomiting, diarrhea, tremor, anxiety and headache. In more severe cases, symptoms consist of heart rythym abnormalities, myocardial infarction and seizures. Due to its common lipolytic effect, caffeine is used in mesotherapy, usually in combination with drugs of similar effect. We presented a patient with acute iatrogenic caffeine poisoning. A 51-year-old woman, with preexisting hypertension and hypertensive cardiomyopathy was subjected to cosmetic treatment in order to remove fat by intradermal caffeine injections. During the treatment the patient felt sickness, an urge to vomit, and a pronounced deterioration of general condition. Upon examination, the patient exhibited somnolence, hypotension and nonsustained ventricular tachycardia, which was sufficient enough evidence for further hospitalization. On admission to the intensive care unit the patient was anxious with increased heart rate, normotensive, with cold, damp skin, and visible traces of injection sites with surrounding hematomas on the anterior abdominal wall. Paroxysmal supraventricular tachycardia (PSVT) on electrocardiographic monitoring was found. The laboratory analysis determined a lowered potassium level of 2.1 mmol/L (normal range 3,5 - 5.2 mmol/L), and a toxicological analysis (liquid chromatography with ultraviolet detection) proved a toxic concentration of caffeine in plasma - 85.03 mg/L (toxic concentration over 25 mg/L). On application of intensive therapy, antiarrhythmics, and substitution of potassium, as well as both symptomatic and supportive therapy, there was a significant recovery. The patient was discharged without any sequele within four days. A presented rare iatrogenic acute caffeine poisoning occured due to massive absorption of caffeine from the subcutaneous adipose tissue into the circulation when injected

  6. Itch elicited by intradermal injection of serotonin, intracisternal injection of morphine, and their synergistic interactions in rats

    PubMed Central

    Moser, Hannah R.; Giesler, Glenn J.

    2014-01-01

    We used the cheek model of itch and pain in rats to determine the dose-response relationships for intradermal injection of serotonin and α methylserotonin on scratching behavior. We also determined the dose-related effects of intracisternally injected morphine on scratching, effects that were greatly reduced by administration of the opiate antagonist naloxone. We then examined the interactions of intradermal injection of serotonin and intracisternal injection of morphine on scratching and found that the two procedures act synergistically to increase itch. These results suggest that morphine applied to the CNS is capable of producing itch and greatly increasing itch originating in the skin (hyperknesis). PMID:24875173

  7. Selective dermal rejuvenation using intradermal injection of carbon dioxide and hyaluronic acid for facial wrinkles.

    PubMed

    Chin, Sae Hoon; Burm, Jin Sik; Kim, Youn Wha

    2013-06-01

    This study assessed selective dermal rejuvenation using sequential intradermal injections of carbon dioxide and hyaluronic acid as a treatment of facial wrinkles. An injection device was designed. After topical anesthesia, 0.1-mL carbon dioxide was gently injected intradermally so as to spread diffusely. A volume of 0.01- to 0.02-mL diluted hyaluronic acid was sequentially injected until the skin rose slightly. Overlapping injections were performed at 3 to 5 mm intervals. This process was repeated until the wrinkles were smoothened. This study included 36 cases of facial wrinkles in 34 patients. The follow-up period was 3 to 11 months. Temporary adverse effects were injection-site pain, mild edema, and redness. Most cases showed obvious improvement in skin thickness, elasticity, and smoothening. Complications included irregularities and hyperpigmentation in 3 cases, and 91% were highly satisfied with the antiwrinkle treatment. This method was a safe, economical, and clinically effective antiwrinkle treatment.

  8. Effect of syngeneic marrow injection upon recovery in sub- and near-lethally irradiated mice

    SciTech Connect

    Boggs, S.S.; Boggs, D.R.; Patrene, K.D.

    1989-06-01

    Mice were given sub-lethal (200-600 cGy) or near-lethal (800 cGy) whole body irradiation and the effect of injecting syngeneic marrow on subsequent hematopoietic recovery was studied. Marrow cell injection enhanced erythropoietic recovery after sub-lethal irradiation as reflected in hematocrit values and rate of appearance of /sup 59/Fe-labeled red cells in blood. However, this enhanced erythropoiesis was only seen in the spleen, and /sup 59/Fe uptake in marrow was reduced. When the irradiation dose was kept constant and the marrow dose increased from 10(5) to 10(6) to 10(7) cells, there was a somewhat erratic increase in spleen /sup 59/Fe and a decrease in marrow /sup 59/Fe uptake. When marrow cell number was kept constant and the dose of irradiation was increased from 200 to 400 to 600 to 800 cGy, there was an exponential increase in spleen /sup 59/Fe uptake but the marrow /sup 59/Fe uptake changed from depressed after lower doses to increased after 800 cGy. Cell injection after sub-lethal irradiation did not increase or decrease granulocytopoiesis. Injection of irradiated marrow cells also reduced marrow erythropoiesis and this was evident after both sub- and near-lethal irradiation. However, injection of irradiated cells did not increase splenic erythropoiesis. Following splenectomy, the depressed marrow erythropoiesis attending injection of viable cells was virtually eliminated but no increase was seen. These data suggest that the injection of autologous or syngeneic marrow may not be effective as a means of accelerating hematopoietic recovery after irradiation unless near-lethal or lethal dose have been received.

  9. Hollow microneedles for intradermal injection fabricated by sacrificial micromolding and selective electrodeposition.

    PubMed

    Norman, James J; Choi, Seong-O; Tong, Nhien T; Aiyar, Avishek R; Patel, Samirkumar R; Prausnitz, Mark R; Allen, Mark G

    2013-04-01

    Limitations with standard intradermal injections have created a clinical need for an alternative, low-cost injection device. In this study, we designed a hollow metal microneedle for reliable intradermal injection and developed a high-throughput micromolding process to produce metal microneedles with complex geometries. To fabricate the microneedles, we laser-ablated a 70 μm × 70 μm square cavity near the tip of poly(lactic acid) (PLA) microneedles. The master structure was a template for multiple micromolded poly(lactic acid-co-glycolic acid) (PLGA) replicas. Each replica was sputtered with a gold seed layer with minimal gold deposited in the cavity due to masking effects. In this way, nickel was electrodeposited selectively outside of the cavity, after which the polymer replica was dissolved to produce a hollow metal microneedle. Force-displacement tests showed the microneedles, with 12 μm thick electrodeposition, could penetrate skin with an insertion force 9 times less than their axial failure force. We injected fluid with the microneedles into pig skin in vitro and hairless guinea pig skin in vivo. The injections targeted 90 % of the material within the skin with minimal leakage onto the skin surface. We conclude that hollow microneedles made by this simple microfabrication method can achieve targeted intradermal injection.

  10. Hollow Microneedles for Intradermal Injection Fabricated by Sacrificial Micromolding and Selective Electrodeposition

    PubMed Central

    Norman, James J.; Choi, Seong-O; Tong, Nhien T.; Aiyar, Avishek R.; Patel, Samirkumar R.; Prausnitz, Mark R.; Allen, Mark G.

    2012-01-01

    Limitations with standard intradermal injections have created a clinical need for an alternative, low-cost injection device. In this study, we designed a hollow metal microneedle for reliable intradermal injection and developed a high-throughput micromolding process to produce metal microneedles with complex geometries. To fabricate the microneedles, we laser-ablated a 70 μm × 70 μm square cavity near the tip of poly(lactic acid-co-glyoclic acid) (PLGA) microneedles. The master structure was a template for multiple micromolded PLGA replicas. Each replica was sputtered with a gold seed layer with minimal gold deposited in the cavity due to masking effects. In this way, nickel was electrodeposited selectively outside of the cavity, after which the polymer replica was dissolved to produce a hollow metal microneedle. Force-displacement tests showed the microneedles, with 12 μm thick electrodeposition, could penetrate skin with an insertion force 9 times less than their axial failure force. We injected fluid with the microneedles into pig skin in vitro and hairless guinea pig skin in vivo. The injections targeted 90% of the material within the skin with minimal leakage onto the skin surface. We conclude that hollow microneedles made by this simple microfabrication method can achieve targeted intradermal injection. PMID:23053452

  11. Best infection control practices for intradermal, subcutaneous, and intramuscular needle injections.

    PubMed Central

    Hutin, Yvan; Hauri, Anja; Chiarello, Linda; Catlin, Mary; Stilwell, Barbara; Ghebrehiwet, Tesfamicael; Garner, Julia

    2003-01-01

    OBJECTIVE: To draw up evidence-based guidelines to make injections safer. METHODS: A development group summarized evidence-based best practices for preventing injection-associated infections in resource-limited settings. The development process included a breakdown of the WHO reference definition of a safe injection into a list of potentially critical steps, a review of the literature for each of these steps, the formulation of best practices, and the submission of the draft document to peer review. FINDINGS: Eliminating unnecessary injections is the highest priority in preventing injection-associated infections. However, when intradermal, subcutaneous, or intramuscular injections are medically indicated, best infection control practices include the use of sterile injection equipment, the prevention of contamination of injection equipment and medication, the prevention of needle-stick injuries to the provider, and the prevention of access to used needles. CONCLUSION: The availability of best infection control practices for intradermal, subcutaneous, and intramuscular injections will provide a reference for global efforts to achieve the goal of safe and appropriate use of injections. WHO will revise the best practices five years after initial development, i.e. in 2005. PMID:12973641

  12. Perichondritis with or without external otitis and intradermal injection: a new therapeutic approach.

    PubMed

    Savastano, Marina; Ferraro, Silvia M; Marioni, Gino

    2009-10-01

    Auricular perichondritis and fiogosis of the external auditory canal are not uncommon pathology of the ear. These inflammatory processes are often accompanied by reactive locoregional lymphadenopathy. An inadequate or insufficient systemic therapy may lead to the persistence of otalgia and of signs of flogosis. The administration of local intradermaltherapy allows a strengthening of the pharmacological effect and a reduction in the quantity of drug used. It provides a rapid improvement in the locoregional signs of infection.Intradermal injection is performed on two pretragral points, two retroauricular points and one in the posterior surface of the pinna. The drugs injected are corticosteroids and antibiotics.The administration of intradermal therapy in the cases presented gave excellent results: control of pain, rapid improvement in the signs of infection, complete recovery from the flogosis, no side-effects.The intradermal lijection of small quantities of drugs allows a rapid and complete recovery from external otitis while the systemic approach leads often to the persistence of the flogosis.

  13. No immunogenicity of IPS cells in syngeneic host studied by in vivo injection and 3D scaffold experiments.

    PubMed

    Thanasegaran, Suganya; Cheng, Zhao; Ito, Sachiko; Nishio, Naomi; Isobe, Ken-ichi

    2013-01-01

    Induced Pluripotent Stem Cells (IPSCs) open the great possibility to employ patient's own tissue to the previously incurable diseases. However these cells can be used in cell therapy only if they are not rejected when transplanted back into the syngeneic host. We found that the injection of iPSCs derived from different ages of mice into syngeneic C57BL/6 mice produced teratoma and was not rejected. Then we cultured iPSCs and myeloid differentiated iPSCs in three-dimensional porous scaffold and transplanted to C57BL/6 mice and BALB/C mice. After transplantation, we could observe the cell density inside the scaffold increased rapidly in syngeneic mice compared to the allogeneic mice indicating the favorable conditions supporting the growth of iPSCs in vivo. Unlike the allogeneic counterpart, we could not observe few infiltrating T cells inside the scaffold of syngeneic mice. These results contribute to the optimistic view of iPSCs for regenerative medicine in near future.

  14. Minocycline inhibits the enhancement of antidromic primary afferent stimulation-evoked vasodilation following intradermal capsaicin injection.

    PubMed

    Gong, Kerui; Yue, Yue; Zou, Xiaoju; Li, Dingge; Lin, Qing

    2010-09-27

    Neurogenic inflammation is induced by inflammatory mediators released in peripheral tissue from primary afferent nociceptors. Our previous studies suggest that neurogenic inflammation induced by intradermal injection of capsaicin results from the enhancement of dorsal root reflexes (DRRs), which involve antidromic activation of dorsal root ganglion (DRG) neurons. Numerous studies have reported the important role of glial modulation in pain. However, it remains unclear whether glial cells participate in the process of neurogenic inflammation-induced pain. Here we tested the role of DRG satellite glial cells (SGCs) in this process in anesthetized rats by administration of a glial inhibitor, minocycline. Electrical stimuli (ES, frequency 10 Hz; duration 1 ms; strength 3 mA) were applied to the cut distal ends of the L4-5 dorsal roots. The stimuli evoked antidromic action potentials designed to mimic DRRs. Local cutaneous blood flow in the hindpaw was measured using a Doppler flow meter. Antidromic ES for 10 min evoked a significant vasodilation that could be inhibited dose-dependently by local administration of the calcitonin gene-related peptide receptor antagonist, CGRP8-37. Pretreatment with capsaicin intradermally injected into the hindpaw 2h before the ES enhanced greatly the vasodilation evoked by antidromic ES, and this enhancement could be reversed by minocycline pretreatment. Our findings support the view that neurogenic inflammation following capsaicin injection involves antidromic activation of DRG neurons via the generation of DRRs. Inhibition of neurogenic inflammation by minocycline is suggested to be associated with its inhibitory effect on SGCs that are possibly activated following capsaicin injection.

  15. A blanching technique for intradermal injection of the hyaluronic acid Belotero.

    PubMed

    Micheels, Patrick; Sarazin, Didier; Besse, Stéphanie; Sundaram, Hema; Flynn, Timothy C

    2013-10-01

    With the proliferation of dermal fillers in the aesthetic workplace have come instructions from various manufacturers regarding dermal placement. Determination of injection needle location in the dermis has in large part been based on physician expertise, product and needle familiarity, and patient-specific skin characteristics. An understanding of the precise depth of dermal structures may help practitioners improve injection specificity. Unlike other dermal fillers that suggest intradermal and deep dermal injection planes, a new hyaluronic acid with a cohesive polydensified matrix may be more appropriate for the superficial dermis because of its structure and its high degree of integration into the dermis. To that end, the authors designed a small study to quantify the depth of the superficial dermis by means of ultrasound and histology. Using ultrasound resources, the authors determined the depths of the epidermis, the dermis, and the reticular dermis in the buttocks of six patients; the authors then extrapolated the depth of the superficial reticular dermis. Histologic studies of two of the patients showed full integration of the product in the reticular dermis. Following determination of injection depths and filler integration, the authors describe a technique ("blanching") for injection of the cohesive polydensified matrix hyaluronic acid into the superficial dermis. At this time, blanching is appropriate only for injection of the cohesive polydensified matrix hyaluronic acid known as Belotero Balance in the United States, although it may have applications for other hyaluronic acid products outside of the United States.

  16. Intradermal application of Aujeszky's disease virus strain Begonia with tocopherol-based adjuvant and a novel design injection device.

    PubMed

    Visser, N; Egger, W; Lütticken, D

    1994-01-01

    Initially the use of intradermal application of Aujeszky's disease vaccines was shown to be very effective. However, for thus far unknown reasons the gI-deleted vaccines were much less efficacious by using this route of vaccination as compared to gI-positive vaccines. By the use of a tocopherol-based adjuvant and an improved design of the intradermal injection device it now appeared feasible to obtain the same efficacy both in specific pathogen free pigs and in pigs with material antibodies as found before when intramuscular administration was performed. With respect to safety we found a complete lack of skin lesions, no adverse systemic reactions (e.g. body temperatures) and no effect on growth rates. Last but not least, the easiness of intradermal injections is of great advantage in large-scale vaccination programs.

  17. Intradermal microneedle delivery of insulin lispro achieves faster insulin absorption and insulin action than subcutaneous injection.

    PubMed

    Pettis, Ronald J; Ginsberg, Barry; Hirsch, Laurence; Sutter, Diane; Keith, Steven; McVey, Elaine; Harvey, Noel G; Hompesch, Marcus; Nosek, Leszek; Kapitza, Christoph; Heinemann, Lutz

    2011-04-01

    This study compared insulin lispro (IL) pharmacokinetics (PK) and pharmacodynamics (PD) delivered via microneedle intradermal (ID) injection with subcutaneous (SC) injection under euglycemic glucose clamp conditions. Ten healthy male volunteers were administered 10 international units (IU) of IL at 3 microneedle lengths (1.25, 1.50, or 1.75 mm) in a randomized, crossover fashion on Days 1-3 followed by a repetitive ID 1.5-mm microneedle dose (Day 4) and an SC dose (Day 5). Microneedle ID delivery resulted in more rapid absorption of IL, with decreased time to maximum insulin concentration (ID vs. SC: 36.0-46.4 vs. 64.3 min, P < 0.05) and higher fractional availability at early postinjection times. ID produced more rapid effects on glucose uptake with shorter times to maximal and early half-maximal glucose infusion rates (GIRs) (ID vs. SC: time to maximum GIR, 106-112 vs. 130 min, P < 0.05; early half-maximal GIR, 29-35 vs. 42 min), increased early GIR area under the curve (AUC), and faster offset of insulin action (shorter time to late half-maximal GIR: 271-287 vs. 309 min). Relative total insulin bioavailability (AUC to 360 min and AUC to infinite measurement) did not significantly differ between administration routes. ID PK/PD parameters showed some variation as a function of needle length. Delivery of ID IL was generally well tolerated, although transient, localized wheal formation and redness were observed at injection sites. Microneedle ID insulin lispro delivery enables more rapid onset and offset of metabolic effect than SC therapy and is safe and well tolerated; further study for insulin therapy is warranted.

  18. Current evidence on intradermal influenza vaccines administered by Soluvia™ licensed micro injection system

    PubMed Central

    Icardi, Giancarlo; Orsi, Andrea; Ceravolo, Antonella; Ansaldi, Filippo

    2012-01-01

    Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability.   Data from clinical trials performed in children, adults <60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination. PMID:22293531

  19. Needle-free jet injector intradermal delivery of fractional dose inactivated poliovirus vaccine: Association between injection quality and immunogenicity.

    PubMed

    Resik, Sonia; Tejeda, Alina; Mach, Ondrej; Sein, Carolyn; Molodecky, Natalie; Jarrahian, Courtney; Saganic, Laura; Zehrung, Darin; Fonseca, Magile; Diaz, Manuel; Alemany, Nilda; Garcia, Gloria; Hung, Lai Heng; Martinez, Yenisleydis; Sutter, Roland W

    2015-10-26

    The World Health Organization recommends that as part of the polio end-game strategy a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries currently using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5 of full dose) IPV (fIPV) by intradermal (ID) injection may reduce costs, but its conventional administration is with Bacillus Calmette-Guerin (BCG) needle and syringe (NS), which is time consuming and technically challenging. We compared injection quality achieved with BCG NS and three needle-free jet injectors and assessed ergonomic features of the injectors. Children between 12 and 20 months of age who had previously received OPV were enrolled in the Camaguey, Cuba study. Subjects received a single fIPV dose administered intradermally with BCG NS or one of three needle-free injector devices: Bioject Biojector 2000® (B2000), Bioject ID Pen® (ID Pen), or PharmaJet Tropis® (Tropis). We measured bleb diameter and vaccine loss as indicators of ID injection quality, with desirable injection quality defined as bleb diameter ≥5mm and vaccine loss <10%. We surveyed vaccinators to evaluate ergonomic features of the injectors. We further assessed the injection quality indicators as predictors of immune response, measured by increase in poliovirus neutralizing antibodies in blood between day 0 (pre-IPV) and 21 (post-vaccination). Delivery by BCG NS and Tropis resulted in the highest proportion of subjects with desirable injection quality; health workers ranked Biojector2000 and Tropis highest for ergonomic features. We observed that vaccine loss and desirable injection quality were associated with an immune response for poliovirus type 2 (P=0.02, P=0.01, respectively). Our study demonstrated the feasibility of fIPV delivery using needle-free injector devices with high acceptability among health workers. We did not observe the indicators of injection quality to be uniformly associated with immune

  20. Intradermal injections of equine allogeneic umbilical cord-derived mesenchymal stem cells are well tolerated and do not elicit immediate or delayed hypersensitivity reactions.

    PubMed

    Carrade, Danielle D; Affolter, Verena K; Outerbridge, Catherine A; Watson, Johanna L; Galuppo, Larry D; Buerchler, Sabine; Kumar, Vijay; Walker, Naomi J; Borjesson, Dori L

    2011-11-01

    BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat acute equine lesions would greatly expand equine cellular therapy options; however, the safety and antigenicity of these cells have not been well-studied. We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC would not elicit acute graft rejection or a delayed-type hypersensitivity response when injected intradermally. METHODS. Six Quarterhorse yearlings received 12 intradermal injections (autologous MSC, allogeneic MSC, positive control and negative control, in triplicate) followed by the same series of 12 injections, 3-4 weeks later, at another site. Wheals were measured and palpated at 0.25, 4, 24, 48, 72 h and 7 days post-injection. Biopsies were obtained at 48 and 72 h and 7 days post-injection. Mixed leukocyte reactions were performed 1 week prior to the first injections and 3 weeks after the second injections. RESULTS. There were no adverse local or systemic responses to two intradermal injections of allogeneic MSC. MSC injection resulted in minor wheal formation, characterized by mild dermatitis, dermal edema and endothelial hyperplasia, that fully resolved by 48-72 h. No differences were noted between allogeneic and autologous MSC. The second injection of MSC did not elicit more significant physical or histomorphologic alterations compared with the first MSC injection. Neither allogeneic nor autologous UCT-derived MSC stimulated or suppressed baseline T-cell proliferation in vitro prior to or after two MSC administrations. CONCLUSIONS. Equine allogeneic UCT MSC may be safely administered intradermally on multiple occasions without eliciting a measurable cellular immune response.

  1. Randomized, double blinded comparative trial of intradermal injections of lignocaine versus N-saline around the knee to relieve pain in patients awaiting total knee replacement.

    PubMed

    Loughnan, Terence Edward; Taverner, Murray G; Webb, Ashley

    2009-05-01

    We report a randomized, double-blinded comparative study assessing the efficacy of local anesthetic with N-saline intradermal blocks around the knee to reduce pain and improve patient satisfaction while waiting for a total knee joint replacement. Patients were offered involvement in this study while on the hospital waiting list for a knee replacement. Eligible patients, after completing a prestudy assessment, received an average of 6.3 (range: 1 to 10) intradermal injections of 0.5 mL either saline or 1% lignocaine injections into tender points around the knee. Patients were assessed at 2 hours and 1 week after the injections. Pain was assessed using 0 to 100 visual analog pain scale. Global perceived effect (satisfaction) was measured on a 7-point Likert scale. Thirty-two of 34 patients attended at 1-week assessment, 24 (75%) felt that they were improved, and 8 (25%) considered they were unchanged or worse. In both the saline and lignocaine groups, 12 of 16 patients felt that they had improved. N-saline proved as effective as lignocaine in reducing knee pain when injected intradermally. Seventy-five percent of patients were improved at 1 week.

  2. Host responses in human skin after conventional intradermal injection or microneedle administration of virus-like-particle influenza vaccine.

    PubMed

    Pearton, Marc; Pirri, Daniela; Kang, Sang-Moo; Compans, Richard W; Birchall, James C

    2013-10-01

    Miniaturized microneedle devices are being developed for painlessly targeting vaccines to the immune cell populations in skin. As skin immunization studies are generally restricted to animal models however, where skin architecture and immunity is greatly different to human, surprisingly little is known about the local human response to intradermal (ID) vaccines. Here surgically excised human skin is used to explore for the first time the complex molecular and cellular host responses to a candidate influenza vaccine comprising nanoparticulate virus-like-particles (VLPs), administered via conventional hypodermic injection or reduced scale microneedles. Responses at the molecular level are determined by microarray analysis (47,296 discrete transcripts) and validated by quantitative PCR (96 genes). Cellular response is probed through monitoring migration of dendritic cells in viable skin tissue. Gene expression mapping, ontological analysis, and qPCR reveal up-regulation of a host of genes responsible for key immunomodulatory processes and host viral response, including cell recruitment, activation, migration, and T cell interaction following both ID and microneedle injection of VLPs; the response from the microneedles being more subtle. Significant morphological and migratory changes to skin dendritic cells are also apparent following microneedle VLP delivery. This is the first study displaying the global, multifaceted immunological events that occur at the site of vaccine deposition in human skin and will subsequently influence the degree and nature of innate and adaptive immune responses. An increased understanding of the detailed similarities and differences in response against antigen administered via different delivery modalities will inform the development of improved vaccines and vaccine delivery systems.

  3. Role of calcitonin gene-related peptide in the sensitization of dorsal horn neurons to mechanical stimulation after intradermal injection of capsaicin.

    PubMed

    Sun, Rui-Qing; Lawand, Nada B; Lin, Qing; Willis, William D

    2004-07-01

    This study was designed to assess the role of calcitonin gene-related peptide (CGRP) and its receptor in the sensitization of dorsal horn neurons induced by intradermal injection of capsaicin in rats. Extracellular recordings were made from wide dynamic range (WDR) dorsal horn neurons with receptive fields on the hindpaw in the lumbar enlargement of anesthetized rats. The background activity and responses to brushing, pressing, and pinching the skin were assessed. A postsuperfusion or a presuperfusion of CGRP(8-37) paradigm was followed. When tested 30 min after capsaicin injection, there was an increase in background activity and responses to brush, press, and pinch applied to the receptive field. Superfusion of CGRP(8-37) into the spinal cord at 45 min after capsaicin injection significantly reversed the increased background activity and responses to brush, press, and pinch applied to the receptive field. On the other hand, spinal superfusion of CGRP(8-37) prior to capsaicin injection prevented the increased background activity and responses to brush, press, and pinch of WDR neurons that occurred following capsaicin injection in control experiments. A sensitization of spinal dorsal horn neurons could also be induced by superfusion of the spinal cord with CGRP. The effect could be blocked by CGRP(8-37) dose-dependently. Collectively, these results suggest that CGRP and its receptors are involved in the spinal cord central sensitization induced by intradermal injection of capsaicin.

  4. The comparison between intradermal injection of abobotulinumtoxinA and normal saline for face-lifting: a split-face randomized controlled trial.

    PubMed

    Wanitphakdeedecha, Rungsima; Ungaksornpairote, Chanida; Kaewkes, Arisa; Rojanavanich, Viboon; Phothong, Weeranut; Manuskiatti, Woraphong

    2016-12-01

    Botulinum toxin type A (BTA) has been approved for the treatment of strabismus, blepharospasm, muscle spasm, cervical dystonia, pain syndrome, glabella wrinkles, and severe primary axillary hyperhidrosis. Intradermal injection of BTA has been used off-label by many clinicians for the purpose of face-lifting effect. Few studies on onabotulinumtoxinA (ONA) demonstrated no clinical efficacy on face-lifting effect when comparing to normal saline solution (NSS). So far, there is no split-face comparison study on face-lifting effect of abobotulinumtoxinA (ABO). To determine the face-lifting effect of ABO intradermal injection and NSS. Twenty-two subjects with symmetrical faces on both facial expression and expressionless were randomly injected with ABO at 1:7 cc dilution (500 unit or one vial in 7 cc of NSS) on one side and NSS on the other side using intradermal injection technique. Standardized photographic documentation was obtained at baseline, and at 2 weeks after treatment. The face-lifting effect was graded by two blinded dermatologists using photographic comparison and rated by the patients. Side effects were also recorded at the end of the study. Face-lifting effect was demonstrated in 40.9% and 4.5% of patients with ABO and NSS, respectively. There was a statistically significant difference in face-lifting effect when comparing between ABO and NSS (P = 0.021). The face-lifting was reported in 50.0% of patients receiving ABO injection. The patients with oval-face shape tended to respond better with ABO (P = 0.046). The odd of face-lifting effect for patients aged younger than 32 was higher than patients aged older than 32 with the odds ratio of 7.9 and 95% confidence interval of 1.1-56.1. Facial asymmetry was found in 22.7% of subjects. This study demonstrated the face-lifting effect of ABO intradermal injection. Patients with oval-face shape and aged younger than 32 tended to respond better. Therefore, patient selection should be emphasized to improve efficacy

  5. A Single-blind, Split-face, Randomized, Pilot Study Comparing the Effects of Intradermal and Intramuscular Injection of Two Commercially Available Botulinum Toxin A Formulas to Reduce Signs of Facial Aging

    PubMed Central

    Sapra, Priya; Sapra, Sheetal; Khanna, Julie; Mraud, Kelli; Bonadonna, Jennifer

    2017-01-01

    Objective: To examine the effectiveness of intradermal botulinum toxin type A injection in improving skin texture and midface lift while reducing pore size and sebum production, as well as investigate the differences in effectiveness between onabotulinumtoxinA and abobotulinumtoxinA using intradermal and intramuscular injection methods. Design: A 16-week, single-blind, split-face, randomized study. Each patient served as their own control, receiving onabotulinumtoxinA and abobotulinumtoxinA randomized to either the left or right side of the face. Patients received intradermal botulinum toxin type A injections at Week 0 and intramuscular botulinum toxin type A injections at Week 2. Participants: Ten women aged 35 to 65 years who exhibited static rhytids in the glabellar and periorbital area. Measurements: The primary endpoint was efficacy of split-face treatment of intradermal and intramuscular onabotulinumtoxinA and abobotulinumtoxinA as assessed by a blinded evaluator using baseline and post-treatment photographs. The secondary endpoints included safety as assessed by adverse events and patient satisfaction measured by questionnaires completed at baseline and post-treatment. Results: Intradermal injection of botulinum toxin type A led to a statistically significant improvement in skin texture (p=0.004) while also resulting in mild midface lift (p=0.024), but did not provide a significant reduction of pore size and sebum production. There was no statistically significant difference between onabotulinumtoxinA and abobotulinumtoxinA when injected intradermally or intramuscularly. Conclusion: Intradermal injection of botulinum toxin type A appears to be a safe and effective therapy that provides an improvement in facial skin texture and midface lift. Registry: clinicaltrials.gov (ID#: NCT02907268). PMID:28367260

  6. Roles of TRPV1 and neuropeptidergic receptors in dorsal root reflex-mediated neurogenic inflammation induced by intradermal injection of capsaicin

    PubMed Central

    Lin, Qing; Li, Dingge; Xu, Xijin; Zou, Xiaoju; Fang, Li

    2007-01-01

    Background Acute cutaneous neurogenic inflammation initiated by activation of transient receptor potential vanilloid-1 (TRPV1) receptors following intradermal injection of capsaicin is mediated mainly by dorsal root reflexes (DRRs). Inflammatory neuropeptides are suggested to be released from primary afferent nociceptors participating in inflammation. However, no direct evidence demonstrates that the release of inflammatory substances is due to the triggering of DRRs and how activation of TRPV1 receptors initiates neurogenic inflammation via triggering DRRs. Results Here we used pharmacological manipulations to analyze the roles of TRPV1 and neuropeptidergic receptors in the DRR-mediated neurogenic inflammation induced by intradermal injection of capsaicin. The degree of cutaneous inflammation in the hindpaw that followed capsaicin injection was assessed by measurements of local blood flow (vasodilation) and paw-thickness (edema) of the foot skin in anesthetized rats. Local injection of capsaicin, calcitonin gene-related peptide (CGRP) or substance P (SP) resulted in cutaneous vasodilation and edema. Removal of DRRs by either spinal dorsal rhizotomy or intrathecal administration of the GABAA receptor antagonist, bicuculline, reduced dramatically the capsaicin-induced vasodilation and edema. In contrast, CGRP- or SP-induced inflammation was not significantly affected after DRR removal. Dose-response analysis of the antagonistic effect of the TRPV1 receptor antagonist, capsazepine administered peripherally, shows that the capsaicin-evoked inflammation was inhibited in a dose-dependent manner, and nearly completely abolished by capsazepine at doses between 30–150 μg. In contrast, pretreatment of the periphery with different doses of CGRP8–37 (a CGRP receptor antagonist) or spantide I (a neurokinin 1 receptor antagonist) only reduced the inflammation. If both CGRP and NK1 receptors were blocked by co-administration of CGRP8–37 and spantide I, a stronger

  7. Safety engineered injection devices for intramuscular, subcutaneous and intradermal injections in healthcare delivery settings: a systematic review and meta-analysis.

    PubMed

    Harb, Alain C; Tarabay, Rami; Diab, Batoul; Ballout, Rami A; Khamassi, Selma; Akl, Elie A

    2015-01-01

    Occupational sharps injuries are associated with transmission of bloodborne viruses to healthcare workers, including hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Similarly reuse of syringes in healthcare settings might transmit these infections between patients. The objective of this study was to systematically review the evidence about the effects of the use by health care workers of two types of safety engineered injection devices, when delivering intramuscular, subcutaneous, or intradermal injectable medications: sharps injury protection syringes and reuse prevention syringes. We included both randomized and non-randomized studies comparing safety syringes to syringes without safety features. Outcomes of interest included needlestick injuries, and HIV, HBV and HCV infections amongst HCWs (for sharps injury prevention syringes) and patients (for reuse prevention syringes). When possible, we conducted meta-analyses using a random-effects model. We tested results for heterogeneity across studies using the I statistic. We assessed the quality of evidence by outcome using the GRADE methodology. We included nine eligible studies: six assessed devices that qualify as sharps injury prevention devices, and three assessed devices that qualify as both injury prevention devices and reuse prevention devices. Eight studies were observational while one was randomized. All studies assessed a single outcome: needle stick injuries among healthcare workers. For sharp injury prevention syringes, the meta-analysis of five studies resulted in a pooled relative risk of 0.54 [0.41, 0.71] for the effect on needlestick injuries per healthcare worker. The associated quality of evidence was rated as moderate. For reuse prevention syringes, data from one study provided a relative risk of 0.40 [0.27, 0.59] for the effect on needlestick injuries per healthcare worker. The associated quality of evidence was rated as moderate. We identified no

  8. Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx(®) (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats.

    PubMed

    Burade, Vinod; Bhowmick, Subhas; Maiti, Kuntal; Zalawadia, Rishit; Jain, Deepak; Rajamannar, Thennati

    2017-05-01

    The liposomal formulation of doxorubicin [doxorubicin (DXR) hydrochloride (HCl) liposome injection, Caelyx(®)] alters the tissue distribution of DXR as compared with nonliposomal DXR, resulting in an improved benefit-risk profile. We conducted studies in murine models to compare the plasma and tissue distribution of a proposed generic DXR HCl liposome injection developed by Sun Pharmaceuticals Industries Limited (SPIL DXR HCl liposome injection) with Caelyx(®). The plasma and tissue distributions of the SPIL and reference DXR HCl liposome injections were compared in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. Different batches and different lots of the same batch of the reference product were also compared with each other. The SPIL and reference DXR HCl liposome injections exhibited generally comparable plasma and tissue distribution profiles in both models. While minor differences were observed between the two products in some tissues, different batches and lots of the reference product also showed some differences in the distribution of various analytes in some tissues. The ratios of estimated free to encapsulated DXR for plasma and tissue were generally comparable between the SPIL and reference DXR HCl liposome injections in both models, indicating similar extents of absorption into the tissues and similar rates of drug release from liposomes. The plasma and tissue distribution profiles of the SPIL and reference DXR HCl liposome injections were shown to be generally comparable. Inconsistencies between the products observed in some tissues were thought to be due to biological variation.

  9. Activation of the cAMP transduction cascade contributes to the mechanical hyperalgesia and allodynia induced by intradermal injection of capsaicin.

    PubMed

    Sluka, K A

    1997-11-01

    1. The spinal role of the cAMP transduction cascade in nociceptive processing was investigated in awake behaving rats (male, Sprague-Dawley) by activating or inhibiting this pathway spinally. Microdialysis fibres were implanted into the dorsal horn to infuse drugs directly to the spinal cord. 2. Animals, without peripheral tissue injury, were tested for responses to repeated applications (10 trials) of von Frey filaments and threshold to mechanical stimulation before and after infusion of 8-bromo-cAMP. In this group of animals treated spinally with 8-br-cAMP (1-10 mM) a dose-dependent hyperalgesia and allodynia were produced. This was manifested as an increased number of responses to 10 trials of von Frey filaments (10, 50, 150, 250 mN) and a decrease in mechanical threshold. 3. A second series of experiments studied the manipulation of the cAMP pathway spinally in a model of tissue injury induced by intradermal injection of capsaicin. Animals were either pre- or post-treated spinally with the adenylate cyclase inhibitor, tetrahydrofuryl adenine (THFA) or the protein kinase A inhibitor, myrosilated protein kinase (14-22) amide (PKI). Injection of capsaicin resulted in an increased number of responses to repeated applications of von Frey filaments and a decrease in threshold to mechanical stimuli outside the site of injection, secondary mechanical hyperalgesia and allodynia. 4. Pre-treatment with either THFA (1 mM) or PKI (5 mM) had no effect on the capsaicin-evoked secondary hyperalgesia and allodynia. 5. In contrast, post-treatment spinally with THFA (0.01-1 mM) or PKI (0.05-50 mM) dose-dependently reduced the mechanical hyperalgesia and allodynia produced by capsaicin injection. Furthermore, the mechanical hyperalgesia and allodynia blocked by the adenylate cyclase inhibitor, THFA (1 mM), was reversed by infusion of 8-bromo-cAMP (0.01-10 mM) in a dose-dependent manner. 6. Thus, this study demonstrates that activation of the cAMP transduction cascade at the spinal

  10. The effects of SDZ NKT 343, a potent NK1 receptor antagonist, on cutaneous responses of primate spinothalamic tract neurones sensitized by intradermal capsaicin injection.

    PubMed

    Rees, H; Sluka, K A; Urban, L; Walpole, C J; Willis, W D

    1998-08-01

    Substance P, acting through neurokinin I receptors, is involved in the processing of nociceptive information in the spinal cord. Sensitization of spinothalamic tract neurons occurs to low-intensity stimuli following capsaicin injection. The current study tested the effects of the novel neurokinin I receptor antagonist, SDZ NKT 343, on the sensitization of spinothalamic tract cells by capsaicin in monkeys. Spinothalamic tract cells from the lumbar enlargement with receptive fields in the hindpaw were isolated and recorded before and after intradermal injection of capsaicin. The background activity and responses to brushing, pressing and pinching the skin were assessed. Thirty minutes after capsaicin injection there was an increase in background activity and responses to brush and pressure applied to the receptive field. Infusion of SDZ NKT 343 (for 30-45 min) significantly reversed the increased response to brushing without affecting the increased background activity or the increased response to pressure. Thus, blockade of neurokinin 1 receptors reduces the sensitized responses to innocuous mechanical stimuli but not to noxious mechanical stimuli.

  11. Role of protein kinase A in phosphorylation of NMDA receptor 1 subunits in dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats.

    PubMed

    Zou, X; Lin, Q; Willis, W D

    2002-01-01

    Protein phosphorylation is a major mechanism for regulation of N-methyl-D-aspartate (NMDA) receptor function. The NMDA receptor 1 subunit (NR1) is phosphorylated by protein kinase A (PKA) on serine 890 and 897. We have recently reported that there is enhanced phosphorylation of NR1 on serine 897 in dorsal horn and spinothalamic tract (STT) neurons after intradermal injection of capsaicin (CAP) in rats [Zou et al. (2000) J. Neurosci. 20, 6989-6997]. Whether or not this phosphorylation, which develops during central sensitization following CAP injection, is mediated by PKA remains to be determined. In this study, western blots and immunofluorescence staining were employed to observe if pretreatment with a PKA inhibitor, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, HCl (H89), blocks the enhanced phosphorylation of NR1 on serine 897 following injection of CAP into the glabrous skin of one hind paw of anesthetized rats. Western blots showed that pretreatment with H89 caused a decrease in CAP-induced phosphorylation of NR1 protein in spinal cord segments L(4)-S(1). In experiments using immunofluorescence staining, the numbers of phospho-NR1-like immunoreactive (p-NR1-LI) neurons seen after CAP injection were significantly decreased in the dorsal horn of the L(4)-L(5) segments on the side ipsilateral to the injection after PKA was inhibited. When STT cells were labeled by microinjection of the retrograde tracer, fluorogold, we found that the proportion of p-NR1-LI STT cells on the side ipsilateral to the injection in the superficial laminae of spinal cord segments L(4)-L(5) was markedly reduced when H89 was administered intrathecally before CAP injection. However, the proportion of p-NR1-LI STT cells in deep laminae was unchanged unless the PKC inhibitor, chelerythrine chloride, was co-administered with H89. Combined with our previous findings, the present results indicate that NR1 in spinal dorsal horn neurons, including the superficial dorsal horn STT

  12. CD4+ T cells dominate the leukocyte infiltration response initiated by intra-dermal injection of phytohemagglutinin into growing feathers in chickens.

    PubMed

    Sullivan, K S; Erf, G F

    2017-10-01

    Phytohemagglutinin (PHA) is commonly used to evaluate cell-mediated immunocompetence. In chickens, PHA is typically injected intra-dermally (i.d.) into the skin (e.g., wing web, wattle, or footpad), and the tissue swelling response is monitored, whereby the extent of tissue swelling positively relates to the individual's cell-mediated immune system capabilities. Although i.d. injected PHA was shown to stimulate mononuclear cell and basophil infiltration to the site of injection, reports on temporal, qualitative, and quantitative aspects of the local cutaneous PHA response are limited. The objective of this study was to use the growing feather (GF) as a cutaneous test site to assess and monitor the type and relative amounts of leukocytes present in the pulp of PHA-injected GF. For this study, male, non-vaccinated Light-brown Leghorn chickens reared at the Arkansas Experiment Station Poultry Health Laboratory were used. At 9 wk of age, the dermis of 20 18-day-old regenerating GF was injected with 10 μL of either PBS diluent or 300 μg/mL PHA-P (5 chickens per treatment). GF were collected from each chicken before (zero) and at 0.25, 1, 2, 3, 4, 5, and 7 d post injection. At each time point, one GF was collected for immunofluorescent staining of pulp cell suspensions and leukocyte population analysis by flow cytometry, and another GF for histological analysis. Histological analysis confirmed participation of granulocytes and mononuclear cells, primarily lymphocytes, in the cutaneous PHA response. As revealed by flow cytometric cell population analysis, T cells, especially CD4+ T cells, constituted the major portion of the mononuclear cell infiltrate. Levels of CD4+ T cells were greatly elevated in PHA-injected GF within 6 h and remained elevated throughout the 7-day examination period. γδ T cells, CD8+ T cells, and B cells also infiltrated in response to PHA although at lower levels and with different time-course patterns from CD4+ T cells. The dominant presence

  13. Increased spinal release of excitatory amino acids following intradermal injection of capsaicin is reduced by a protein kinase G inhibitor.

    PubMed

    Sluka, K A; Willis, W D

    1998-07-06

    Second messengers have been shown to play a role in the release of neurotransmitters presynaptically in several brain regions and cell types. This study was designed to test the hypothesis that the increased release of aspartate and glutamate that occurs after injection of capsaicin is dependent on activation of the cAMP and the cGMP transduction cascades. A microdialysis fiber was implanted into the dorsal horn of the spinal cord for collection of extracellular fluid and for administration of drugs to the spinal cord. Dialysate samples were collected before and after injection of capsaicin and after infusion of inhibitors of protein kinase G (PKG; KT5823) or protein kinase A (PKA; H89). KT5823, H89, or artificial cerebrospinal fluid (ACSF; control) were administered after injection of capsaicin to reduce the increased release of aspartate and glutamate. At the time of injection of capsaicin, there is an increase in release of aspartate (191+/-21%) and glutamate (194+/-14%). This increased release is maintained through 2.5 h for both glutamate and aspartate at approximately 125% to 150%. The increase in aspartate and glutamate concentrations that occurs after capsaicin injection was reduced back to baseline after spinal infusion of the PKG inhibitor, KT5823. Blockade of PKA had no effect on the increased release of aspartate and glutamate. Thus, the current data support a role for the cGMP-PKG pathway in the control of neurotransmitter release in vivo.

  14. A new biolistic intradermal injector

    NASA Astrophysics Data System (ADS)

    Brouillette, M.; Doré, M.; Hébert, C.; Spooner, M.-F.; Marchand, S.; Côté, J.; Gobeil, F.; Rivest, M.; Lafrance, M.; Talbot, B. G.; Moutquin, J.-M.

    2016-01-01

    We present a novel intradermal needle-free drug delivery device which exploits the unsteady high-speed flow produced by a miniature shock tube to entrain drug or vaccine particles onto a skin target. A first clinical study of pain and physiological response of human subjects study is presented, comparing the new injector to intramuscular needle injection. This clinical study, performed according to established pain assessment protocols, demonstrated that every single subject felt noticeably less pain with the needle-free injector than with the needle injection. Regarding local tolerance and skin reaction, bleeding was observed on all volunteers after needle injection, but on none of the subjects following powder injection. An assessment of the pharmacodynamics, via blood pressure, of pure captopril powder using the new device on spontaneously hypertensive rats was also performed. It was found that every animal tested with the needle-free injector exhibited the expected pharmacodynamic response following captopril injection. Finally, the new injector was used to study the delivery of an inactivated influenza vaccine in mice. The needle-free device induced serum antibody response to the influenza vaccine that was comparable to that of subcutaneous needle injection, but without requiring the use of an adjuvant. Although no effort was made to optimize the formulation or the injection parameters in the present study, the novel injector demonstrates great promise for the rapid, safe and painless intradermal delivery of systemic drugs and vaccines.

  15. Prospective randomized clinical trial comparing intradermal, intraparenchymal, and subareolar injection routes for sentinel lymph node mapping and biopsy in breast cancer.

    PubMed

    Povoski, Stephen P; Olsen, Johannes O; Young, Donn C; Clarke, Johannah; Burak, William E; Walker, Michael J; Carson, William E; Yee, Lisa D; Agnese, Doreen M; Pozderac, Rodney V; Hall, Nathan C; Farrar, William B

    2006-11-01

    Multiple injection routes, including intradermal (ID), intraparenchymal (IP), and subareolar (SA), are used for 99mTc-sulfur colloid administration for sentinel lymph node (SLN) mapping and biopsy in breast cancer. The aim of this study was to compare localization by ID, IP, and SA injection routes based on preoperative lymphoscintigraphy and intraoperative identification. Four hundred prospectively randomized breast cancers underwent SLN mapping and biopsy. Preoperative lymphoscintigraphy demonstrated localization to the axilla in 126/133 (95%) ID, 82/132 (62%) IP, and 96/133 (72%) SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.081 IP vs. SA), with a mean duration of preoperative lymphoscintigraphy of 139 +/- 18 minutes. Mean time to first localization when localization was demonstrated on preoperative lymphoscintigraphy was 8 +/- 14 minutes for ID, 53 +/- 49 for IP, and 22 +/- 29 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.003 IP vs. SA). Intraoperative identification of a SLN at the time of SLN biopsy was successful in 133/133 (100%) ID, 121/134 (90%) IP, and 126/133 (95%) SA (P < 0.001 ID vs IP; P = 0.014 ID vs. SA; P = 0.168 IP vs. SA), with a mean time from injection of 99mTc-sulfur colloid to start of SLN biopsy of 288 +/- 71 minutes. Mean intraoperative time to harvest the first SLN was 9 +/- 4 minutes for ID, 13 +/- 6 for IP, and 12 +/- 6 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.410 IP vs. SA). The ID injection route demonstrated a significantly greater frequency of localization, decreased time to first localization on preoperative lymphoscintigraphy, and decreased time to harvest the first SLN. This represents the first prospective randomized clinical trial to confirm superiority of the ID route for administration of 99mTc-sulfur colloid during SLN mapping and biopsy in breast cancer.

  16. Intradermal antigen tests in psoriasis.

    PubMed

    McFadden, J P; Powles, A V; Baker, B S; Valdimarsson, H; Fry, L

    1990-01-01

    To assess whether elicitation of delayed hypersensitivity may be superior to trauma in inducing the Koebner reaction in psoriasis, 12 affected patients and 9 control subjects were tested with 0.1 ml intradermal injections of streptokinase/streptodornase (20 mu/5 mu per 0.1 ml), PPD (1 in 1000) and saline control solutions in a double-blind study; Koebner status was also established in the psoriatic patients. Injected sites were examined at 48 h and 7, 14, 21 and 28 days for local development of psoriasis, erythema and induration (diameter). One patient was Koebner-positive and developed psoriasis at all three injection sites. The other, Koebner-negative psoriatic subjects did not develop psoriasis locally. However, compared with non-psoriatic controls they showed a marked delay in resolution of the delayed hypersensitivity reaction to the PPD antigen and a similar but less marked phenomenon was observed for streptokinase/streptodornase. These findings indicate that intradermal antigen, of the nature and amount used in this study, is no more effective in inducing the Koebner phenomenon than injury alone. However, the ability of psoriasis patients to switch off cell-mediated immune reaction appears to be impaired.

  17. Fixed drug eruption and intradermal provocation tests.

    PubMed

    Mahboob, Atiya; Haroon, Tahir Saeed; Iqbal, Zafar; Saleemi, Munir Akhtar; Munir, Asma

    2008-12-01

    To determine the role of Intradermal Provocation (IDP) tests in Fixed Drug Eruption (FDE). Quasi-experimental study. Dermatology Unit, Shaikh Zayed Hospital, Lahore, from August 2004 to July 2006. The tests were performed in 96 patients in two stages. At stage I, suspected drugs were given intradermally. Changes at injection site in FDE lesions or any systemic effects were observed. In patients showing no response to IDP, Oral Provocation (OP) was performed (stage II) and its effects in FDE lesions or any systemic effect were observed. The positive response of FDE lesions after IDP and OP were compared with local changes at injection site. Control intradermal tests were repeated in normal persons with drugs and in FDE patients with distilled water on normal skin. At stage I, 46 positive cases had local signs of erythematous indurated nodule with or without hemorrhagic centre, urticarial weal with hemorrhagic centre and erythematous indurated nodule with central vesicle. At stage II, 41 patients had similar local signs. The changes at injection site to those of FDE lesions were compared. Z-test for proportions showed no significant difference between groups (p-value > 0.05). Control tests were negative. The drug producing erythematous indurated nodule with or without hemorrhagic centre, vesicle or urticarial weal with hemorrhagic centre at injection site was the most likely drug causing fixed eruption.

  18. Natural History of Mouse Syngeneic Lymphoma

    PubMed Central

    Jurin, Mislav; Drewinko, Benjamin

    1974-01-01

    The morphologic changes in lymphoreticular tissues and development of antitumor immune reactions of specific pathogen-free mice injected with syngeneic lymphoma cells were sequentially analyzed. The regional (right inguinal) lymph node demonstrated mild changes indicative of immunologic response. Systemic lymph nodes revealed a moderate degree of immune response on morphologic basis. The spleen was the site of marked activity, characterized by the presence of large pyroninophilic cells and germinal centers. Foci of necrosis in the local tumor accompanied by mature lymphocytes suggested cell-mediated immune rejection. Mice developed circulating antibodies 2 days after implantation. No antibodies were demonstrated attached to fresh tumor cells. Lymphocyte cytotoxic activity was demonstrated beginning on day 4. Both cytotoxic activity and circulating antibodies were no longer detectable after the third week following tumor implantation. Tumor-bearing mice also had an impaired capacity to mount a primary immune reaction to sheep red blood cells. The spleen demonstrated a marked loss of lymphocytes and the subsequent appearance of masses of amyloid material. It is suggested that amyloidosis in lymphoreticular organs is the result of a derangement in the immune response of the host following a prolonged and sustained antigenic stimulation. It appears that in syngeneic pathogen-free mice the spleen plays the major role in immune rejection mechanisms while the draining node only plays a modest role. ImagesFig 3Fig 4Fig 5Fig 1Fig 2 PMID:4614670

  19. Use of intradermal botulinum toxin to reduce sebum production and facial pore size.

    PubMed

    Shah, Anil R

    2008-09-01

    Review the safety profile and subjective efficacy of intradermal botulinum toxin type A in facial pore size and sebum production. Retrospective analysis of 20 patients. Twenty consecutive patients with a single application of intradermal botulinum toxin type A were examined: Patients (17/20) noted an improvement in sebum production and a decrease in pores size at 1 month after injection. No complications were observed, and 17/20 patients were satisfied with the procedure. Preliminary data suggests that intradermal botulinum toxin may play a role in decreasing sebum production. Further quantitive study may be necessary to determine effects of intradermal botulinum toxin on pore size.

  20. Intradermal naked plasmid DNA immunization: mechanisms of action.

    PubMed

    Elnekave, Mazal; Furmanov, Karina; Hovav, Avi-Hai

    2011-08-01

    Plasmid DNA is a promising vaccine modality that is regularly examined in prime-boost immunization regimens. Recent advances in skin immunity increased our understanding of the sophisticated cutaneous immune network, which revived scientific interest in delivering vaccines to the skin. Intradermal administration of plasmid DNA via needle injection is a simple and inexpensive procedure that exposes the plasmid and its encoded antigen to the dermal immune surveillance system. This triggers unique mechanisms for eliciting local and systemic immunity that can confer protection against pathogens and tumors. Understanding the mechanisms of intradermal plasmid DNA immunization is essential for enhancing and modulating its immunogenicity. With regard to vaccination, this is of greater importance as this routine injection technique is highly desirable for worldwide immunization. This article will focus on the current understanding of the mechanisms involved in antigen expression and presentation during primary and secondary syringe and needle intradermal plasmid DNA immunization.

  1. Effect of syngeneic thymocytes on proliferation of the small intestinal epithelium in mice

    SciTech Connect

    Shmakov, A.N.; Aparovich, G.G.; Trufakin, V.A.

    1986-12-01

    This paper describes the study of the action of syngeneic thymocytes on proliferation of the epithelium of the mouse small intestine. The mice were injected with /sup 3/H-thymidine in the experiments. Under the experimental conditions presented here, syngeneic thymocytes can reduce the number of DNA-synthesizing cells in the intestinal epithelium, causing narrowing of the zone of proliferation and enlargement of the zone of differentiation of the enterocytes.

  2. Delayed Response To Intradermal Test by Benzathine Penicilin.

    PubMed

    Pavitran, K

    1981-01-01

    A delayed, Tuberculin type response to intradermal (ID) test with benzathine penicillin is described in a 50 year old female. She did not develop any sign of drug reaction on receiving.intramuscular injection of that drug. None of the 65 patients who were studied in detail for the ID test response to various penicillins showed such a delayed response.

  3. Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery.

    PubMed

    Best, Simon R; Peng, Shiwen; Juang, Chi-Mou; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R; Wu, T-C; Pai, Sara I

    2009-09-04

    DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination--conventional intramuscular injection, electroporation-mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery--in the ability to generate antigen-specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin's role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials.

  4. Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery

    PubMed Central

    Best, Simon R.; Peng, Shiwen; Juang, Chi-Mou; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.; Pai, Sara I.

    2009-01-01

    DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC Class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination – conventional intramuscular injection, electroporation mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery - in the ability to generate antigen specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin’s role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials. PMID:19622402

  5. Intradermal delivery of vaccines: potential benefits and current challenges

    PubMed Central

    Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D

    2011-01-01

    Abstract Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination. PMID:21379418

  6. Intradermal delivery of vaccines: potential benefits and current challenges.

    PubMed

    Hickling, J K; Jones, K R; Friede, M; Zehrung, D; Chen, D; Kristensen, D

    2011-03-01

    Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination.

  7. Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future

    PubMed Central

    Levin, Yotam; Kochba, Efrat; Hung, Ivan; Kenney, Richard

    2015-01-01

    Intradermal immunization has become a forefront of vaccine improvement, both scientifically and commercially. Newer technologies are being developed to address the need to reduce the dose required for vaccination and to improve the reliability and ease of injection, which have been major hurdles in expanding the number of approved vaccines using this route of administration. In this review, 7 y of clinical experience with a novel intradermal delivery device, the MicronJet600, which is a registered hollow microneedle that simplifies the delivery of liquid vaccines, are summarized. This device has demonstrated both significant dose-sparing and superior immunogenicity in various vaccine categories, as well as in diverse subject populations and age groups. These studies have shown that intradermal delivery using this device is safe, effective, and preferred by the subjects. Comparison with other intradermal devices and potential new applications for intradermal delivery that could be pursued in the future are also discussed. PMID:25745830

  8. Ultrasonic assessment of cutaneous atrophy caused by intradermal corticosteroids.

    PubMed

    Gomez, E C; Berman, B; Miller, D L

    1982-12-01

    A noninvasive technique of pulsed ultrasound was used to determine the long-term changes in skin thickness resulting from intradermal injections of triamcinolone acetonide (TA). Injections of 0.1 ml of either saline or a suspension containing 5 mg/ml or 10 mg/ml of TA were made at selected sites on the forearms of two human volunteers. The corticosteroid-treated sites showed a maximal decrease of 30% to 40% of the original skin thickness at 4 to 8 weeks after a single injection. A transient thinning was observed at control sites injected with saline. A greater degree of thinning was seen at the site injected with 10 mg/ml of TA as compared to the site injected with 5 mg/ml of TA. The thinning at the corticosteroid injection sites persisted at least 18 weeks after the single corticosteroid injection but had approached normal thickness values by 44 weeks following treatment. Pulsed ultrasound may be useful as a noninvasive technique for monitoring the effects of intradermally injected corticosteroids on human skin thickness and may also be useful in assessing intrinsic atrophogenic potentials of different corticosteroid molecules in human skin and the duration of action of various injectable formulations of a corticosteroid.

  9. Development of a syngeneic mouse model of epithelial ovarian cancer

    PubMed Central

    2010-01-01

    Background Most cases of ovarian cancer are epithelial in origin and diagnosed at advanced stage when the cancer is widely disseminated in the peritoneal cavity. The objective of this study was to establish an immunocompetent syngeneic mouse model of disseminated epithelial ovarian cancer (EOC) to facilitate laboratory-based studies of ovarian tumor biology and preclinical therapeutic strategies. Methods Individual lines of TgMISIIR-TAg transgenic mice were phenotypically characterized and backcrossed to inbred C57BL/6 mice. In addition to a previously described line of EOC-prone mice, two lines (TgMISIIR-TAg-Low) were isolated that express the oncogenic transgene, but have little or no susceptibility to tumor development. Independent murine ovarian carcinoma (MOVCAR) cell lines were established from the ascites of tumor-bearing C57BL/6 TgMISIIR-TAg transgenic mice, characterized and tested for engraftment in the following recipient mice: 1) severe immunocompromised immunodeficient (SCID), 2) wild type C57BL/6, 3) oophorectomized tumor-prone C57BL/6 TgMISIIR-TAg transgenic and 4) non-tumor prone C57BL/6 TgMISIIR-TAg-Low transgenic. Lastly, MOVCAR cells transduced with a luciferase reporter were implanted in TgMISIIR-TAg-Low mice and in vivo tumor growth monitored by non-invasive optical imaging. Results Engraftment of MOVCAR cells by i.p. injection resulted in the development of disseminated peritoneal carcinomatosis in SCID, but not wild type C57BL/6 mice. Oophorectomized tumor-prone TgMISIIR-TAg mice developed peritoneal carcinomas with high frequency, rendering them unsuitable as allograft recipients. Orthotopic or pseudo-orthotopic implantation of MOVCAR cells in TgMISIIR-TAg-Low mice resulted in the development of disseminated peritoneal tumors, frequently accompanied by the production of malignant ascites. Tumors arising in the engrafted mice bore histopathological resemblance to human high-grade serous EOC and exhibited a similar pattern of peritoneal

  10. Intradermal allergy test reactions (image)

    MedlinePlus

    ... determine whether an individual is allergic to a specific allergen. The test involves injection of a small amount of the suspected allergen under the surface of the skin. After about 20 minutes the area is examined for a reaction at the site. ...

  11. A New Biolistic Intradermal Injector Based on a Miniature Shock Tube

    NASA Astrophysics Data System (ADS)

    Brouillette, M.

    Intradermal powder injection is an emerging technology for the needlefree delivery of a potentially wide array of drugs and vaccines. Although needle injection of liquids is widespread principally because of its low cost, this delivery method is painful, generates dangerous medical waste and can cause contamination. Various technologies have been developed to address these shortcomings, amongst them creams, patches, inhalers and liquid jet injectors, each with their own severe limitations.

  12. Inhibition of effector antigen-specific T cells by intradermal administration of heme oxygenase-1 inducers.

    PubMed

    Simon, Thomas; Pogu, Julien; Rémy, Séverine; Brau, Frédéric; Pogu, Sylvie; Maquigneau, Maud; Fonteneau, Jean-François; Poirier, Nicolas; Vanhove, Bernard; Blancho, Gilles; Piaggio, Eliane; Anegon, Ignacio; Blancou, Philippe

    2017-03-22

    Developing protocols aimed at inhibiting effector T cells would be key for the treatment of T cell-dependent autoimmune diseases including type 1 autoimmune diabetes (T1D) and multiple sclerosis (MS). While heme oxygenase-1 (HO-1) inducers are clinically approved drugs for non-immune-related diseases, they do have immunosuppressive properties when administered systemically in rodents. Here we show that HO-1 inducers inhibit antigen-specific effector T cells when injected intradermally together with the T cell cognate antigens in mice. This phenomenon was observed in both a CD8(+) T cell-mediated model of T1D and in a CD4(+) T cell-dependent MS model. Intradermal injection of HO-1 inducers induced the recruitment of HO-1(+) monocyte-derived dendritic cell (MoDCs) exclusively to the lymph nodes (LN) draining the site of intradermal injection. After encountering HO-1(+)MoDCs, effector T-cells exhibited a lower velocity and a reduced ability to migrate towards chemokine gradients resulting in impaired accumulation to the inflamed organ. Intradermal co-injection of a clinically approved HO-1 inducer and a specific antigen to non-human primates also induced HO-1(+) MoDCs to accumulate in dermal draining LN and to suppress delayed-type hypersensitivity. Therefore, in both mice and non-human primates, HO-1 inducers delivered locally inhibited effector T-cells in an antigen-specific manner, paving the way for repositioning these drugs for the treatment of immune-mediated diseases.

  13. Management of amiodarone extravasation with intradermal hyaluronidase.

    PubMed

    Fox, Ashley N; Villanueva, Ruben; Miller, Jamie L

    2017-10-01

    The case of a patient who experienced extravasation while receiving amiodarone via a peripheral infusion and was treated with intradermal hyaluronidase is reported. A 60-year-old Caucasian man arrived at the emergency department after a motor vehicle collision. The patient was noted to have a subdural hematoma, multiple rib fractures, sternal body fracture, abdominal wall injury, left clavicle fracture, right humerus fracture, and vertebral fractures. His medical history included hypertension, atrial fibrillation, and stroke with residual right-sided weakness. On postoperative day 1, the patient developed atrial fibrillation and was started on i.v. amiodarone. Treatment resulted in conversion to sinus rhythm, but the patient again developed atrial fibrillation on postoperative day 5. During the morning hours of postoperative day 6, the patient experienced a peripheral i.v. line extravasation of amiodarone in his left arm. The amiodarone drip was discontinued, and amiodarone 400 mg orally twice daily was started. The nursing staff was instructed to treat the patient for the amiodarone extravasation with traditional nonpharmacologic measures, including warm compresses and elevation of the extremity. After extravasation, the patient reported severe pain at the site. Due to the patient's continued complaints of pain and the expanding area of induration, the interdisciplinary team elected to proceed with intradermal hyaluronidase. The patient reported significantly decreased pain and was discharged to inpatient rehabilitation on postoperative day 10 without any significant adverse effects. Administration of intradermal hyaluronidase after amiodarone extravasation was associated with decreased expansion of erythema and warmth as well as an improvement in patient-reported pain scores without any noted adverse effects. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  14. A dose- and time-controllable syngeneic animal model of breast cancer microcalcification.

    PubMed

    Liu, Fangbing; Misra, Preeti; Lunsford, Elaine P; Vannah, Joanne T; Liu, Yuxia; Lenkinski, Robert E; Frangioni, John V

    2010-07-01

    The development of novel diagnostic agents for the detection of breast cancer microcalcifications requires a reliable animal model. Based on previous work from our group, we hypothesized that a single systemic injection of recombinant bone morphogenetic protein-2 (rBMP-2) could be used to create such a model. The cDNA encoding mature human BMP-2 was expressed in BL21(DE3) bacteria, purified to homogeneity, and refolded as a dimer. Bioactivity was confirmed using a C2C12 alkaline phosphatase assay. rBMP-2 was radiolabeled with (99m)Tc, and its biodistribution and clearance were quantified after both intravenous (IV) and intraperitoneal (IP) injection. Fischer 344 rats bearing syngeneic R3230 breast tumors received a single intraperitoneal injection of rBMP-2 at a specified dose. Tumor microcalcification was quantified over time using micro-single photon emission computed tomography (SPECT) and microcomputed tomography (CT). rBMP-2 could be expressed in E. coli at high levels, isolated at >95% purity, and refolded to a bioactive dimer. Beta-phase half-life was 30.5 min after IV administration and 47.6 min after IP administration. Renal excretion was the primary mode of clearance. A single IP injection of >or=50 microg rBMP-2 when tumors were not yet palpable resulted in dose-dependent microcalcification in 8 of 8 R3230 tumors. No calcification was found in control tumors or in normal tissues and organs of animals injected with rBMP-2. Tumor calcification increased progressively between weeks 2 and 4 post-rBMP-2 injection. A single IP injection of rBMP-2 in rats bearing a syngeneic breast cancer will produce dose-dependent and time-dependent microcalcifications. This animal model lays the foundation for the development of novel diagnostic radiotracers for breast cancer.

  15. Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study.

    PubMed

    Van Damme, Pierre; Arnou, Robert; Kafeja, Froukje; Fiquet, Anne; Richard, Patrick; Thomas, Stéphane; Meghlaoui, Gilles; Samson, Sandrine Isabelle; Ledesma, Emilio

    2010-05-26

    Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly. Elderly volunteers (age > or = 65 years) were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 microg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 microg HA/strain/0.5-ml dose) adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 +/- 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI) and single radial haemolysis (SRH) methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine. A total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397). Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53) using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1%) than the adjuvanted vaccine (33.8%) but these reactions were mild and of short duration. The immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the immune properties of the skin appears to be an

  16. Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study

    PubMed Central

    2010-01-01

    Background Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly. Methods Elderly volunteers (age ≥ 65 years) were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 μg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 μg HA/strain/0.5-ml dose) adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 ± 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI) and single radial haemolysis (SRH) methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine. Results A total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397). Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53) using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1%) than the adjuvanted vaccine (33.8%) but these reactions were mild and of short duration. Conclusions The immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the immune properties of

  17. Bone marrow transfusions in previously irradiated, hematologically normal syngeneic mice

    SciTech Connect

    Brecher, G.; Lawce, H.; Tjio, J.H.

    1981-03-01

    Transfusion of syngeneic marrow into normal, nonirradiated recipients results only in minimal proliferation of donor cells. However, irradiated recipients, restored to hematologic normalcy by an initial marrow transfusion, subsequently sustain proliferation which replaces approximately 10% of endogenous marrow after a single transfusion of 4 x 10/sup 7/ marrow cells of the same strain as the host. Cells from histoincompatible donors proliferate only rarely or minimally in the marrows of these irradiated, but hematologically normal recipients without reirradiation. Syngeneic male donor cells proliferate in irradiated and restored female mice, while female donor cells fail to proliferate in the marrow of syngeneic male recipients. A possible explanation is that transfused female cells respond immunologically to the abundant H-Y antigen in the male environment and are eliminated as a result.

  18. Toward intradermal vaccination: preparation of powder formulations by collapse freeze-drying.

    PubMed

    Etzl, Elsa E; Winter, Gerhard; Engert, Julia

    2014-03-01

    Intradermal powder immunization is an emerging technique in vaccine delivery. The purpose of this study was to generate powder particles for intradermal injection by freeze-drying and subsequent cryo-milling. Two different freeze-drying protocols were compared, a moderate freeze-drying cycle and an aggressive freeze-drying cycle, which induced a controlled collapse of the sugar matrix. Ovalbumin served as model antigen. The influence of collapse drying and cryo-milling on particle morphology and protein stability was investigated. Cryo-milling generated irregularly shaped particles of size 20-70 µm. The recovery of soluble monomer of ovalbumin was not changed during freeze-drying and after cryo-milling, or after 12 months of storage at 2-8 °C. A slight increase in higher molecular weight aggregates was found in formulations containing the polymer dextran after 12 months of storage at 50 °C. Light obscuration measurements showed an increase in cumulative particle counts after cryo-milling that did not further increase during storage at 2-8 °C for 12 months. The applicability of the cryo-milling process to other therapeutic proteins was shown using recombinant human granulocyte-colony stimulating factor. Collapse freeze-drying and subsequent cryo-milling allows the generation of particles suitable for intradermal powder injection.

  19. Intradermal normal saline solution, self-selected music, and insertion difficulty effects on intravenous insertion pain.

    PubMed

    Jacobson, A F

    1999-01-01

    To examine the effect of listening to self-selected music versus an intradermal injection of normal saline solution on the intensity and distress of intravenous (IV) catheter insertion pain. Prospective, randomized, controlled study. Inpatient and outpatient units in 2 university-affiliated southwestern medical centers. One hundred ten adult inpatients and outpatients undergoing IV therapy. Pain intensity, pain distress, and IV insertion difficulty visual analog scales. Patients were randomly assigned to receive an intradermal injection of normal saline solution, listen with headphones to self-selected music, or be in a control group for IV insertion. A MANOVA revealed no statistically significant multivariate or univariate differences in pain by treatment group, but significantly higher pain distress scores with failed IV insertions. The pain intensity and distress scores were significantly higher in the saline solution group when compared with the music and control groups combined. Insertion difficulty was significantly positively correlated with pain intensity and distress for the entire sample, with weak, nonsignificant correlations in the music group. Intradermal unpreserved saline solution contributes to greater pain intensity and distress, greater insertion difficulty, and a higher failure rate than the use of music or routine IV insertion. Listening to preferred music attenuates the effect of insertion difficulty on IV insertion pain. Intravenous insertion attempts were unsuccessful in more than one third of the subjects, resulting in higher pain distress scores. Further research is needed on interventions to reduce IV insertion pain and on factors contributing to IV insertion failure.

  20. Aero-allergens in canine atopic dermatitis in southeastern Australia based on 1000 intradermal skin tests.

    PubMed

    Mueller, R S; Bettenay, S V; Tideman, L

    2000-06-01

    To determine the most relevant aero-allergens involved in canine atopic dermatitis in southeastern Australia and provide information about these aero-allergens to the general practitioner. Dogs presented to the Animal Skin & Allergy Clinic with history and clinical signs of atopic dermatitis were injected intradermally with 38 different allergens and negative and positive control. Intradermal skin tests in 1000 dogs were retrospectively evaluated. One third of all patients reacted to the house dust mite Dermatophagoides farinae. Allergens reacting in more than 15% of the patients were wheat (Triticum aestivum), sweet vernal (Anthoxanthum odoratum), English couch (Agropyron repens), yellow dock (Rumex crispus), Mexican tea (Chenopodium ambrosioides), plantain (Plantago lanceolata), melaleuca (Melaleuca quinquenervia) and peppercorn (Schimus spp). House dust mites are the most common allergens in canine atopic dermatitis in southeastern Australia and D farinae is involved most frequently. However, a number of grass, weed and tree pollens also are involved regularly.

  1. Syngeneic anti-idiotypic monoclonal antibodies to an anti-NeuGc-containing ganglioside monoclonal antibody.

    PubMed

    Vázquez, A M; Pérez, A; Hernández, A M; Macías, A; Alfonso, M; Bombino, G; Pérez, R

    1998-12-01

    An IgM monoclonal antibody (MAb), named P3, has the characteristic to react specifically with a broad battery of N-glycolyl containing-gangliosides and with antigens expressed on breast tumors. When this MAb was administered alone in syngeneic mice, an specific IgG anti-idiotypic antibody (Ab2) response was induced, this Ab2 response was increased when P3 MAb was injected coupled to a carrier protein and in the presence of Freund's adjuvant. Spleen cells from these mice were used in somatic-cell hybridization experiments, using the murine myeloma cell line P3-X63-Ag8.653 as fusion partner. Five Ab2 MAbs specific to P3 MAb were selected. These IgG1 Ab2 MAbs were able to block the binding of P3 MAb to GM3(NeuGc) ganglioside and to a human breast carcinoma cell line. Cross-blocking experiments demonstrated that these Ab2 MAbs are recognizing the same or very close sites on the Abl MAb. The five Ab2 MAbs were injected into syngeneic mice and four of them produced strong anti-anti-idiotypic antibody (Ab3) response. While these Ab2 MAbs were unable to generate Ab3 antibodies with the same antigenic specificity than P3 MAb, three of them induced antibodies bearing P3 MAb idiotopes (Ag-Id+ Ab3). These results demonstrated that these Ab2 MAbs are not "internal image" antibodies, but they could define "regulatory idiotopes."

  2. Intradermal administration of fluorescent contrast agents for delivery to axillary lymph nodes

    NASA Astrophysics Data System (ADS)

    Rasmussen, John C.; Meric-Berstam, Funda; Krishnamurthy, Savitri; Tan, I.-Chih; Zhu, Banghe; Wagner, Jamie L.; Babiera, Gildy V.; Mittendorf, Elizabeth A.; Sevick-Muraca, Eva M.

    2014-05-01

    In this proof-of-concept study we seek to demonstrate the delivery of fluorescent contrast agent to the tumor-draining lymph node basin following intraparenchymal breast injections and intradermal arm injection of micrograms of indocyanine green in 20 breast cancer patients undergoing complete axillary lymph node dissection. Individual lymph nodes were assessed ex vivo for presence of fluorescent signal. In all, 88% of tumor-negative lymph nodes and 81% of tumor-positive lymph nodes were fluorescent. These results indicate that future studies utilizing targeted fluorescent contrast agents may demonstrate improved surgical and therapeutic intervention.

  3. Intradermal delivery for vaccine dose sparing: overview of current issues.

    PubMed

    Zehrung, Darin; Jarrahian, Courtney; Wales, Amy

    2013-07-25

    There is a wide range of methods and technologies aimed at improving human vaccine products and the way they are delivered. Some of these have the potential to increase vaccine effectiveness in specific populations and may furthermore help to increase vaccine access, reduce costs, and ease the logistical burdens of immunization programs, especially in low-resource settings. One strategy under evaluation is the use of intradermal (ID) delivery of vaccines, which has been shown to result in dose sparing with some vaccines. Novel ID delivery devices could enable needle-free and therefore safer and more reliable ID administration than current ID injection methods, facilitating ID delivery and dose sparing with existing or new vaccines. There are promising clinical data with some vaccines that highlight the potential of reduced-dose immunization via the ID route. And more studies are under way. However, a number of clinical and technical research as well as operational challenges exist, including establishing the optimal doses for different vaccines, reformulating to adjust antigen concentration or add preservatives, matching vaccine vial volume to session size, working with vaccine manufacturers to achieve regulatory clearance for ID delivery, and developing ID delivery devices suitable for the varying scenarios of use of different vaccines. These will need to be addressed before the benefits of ID delivery and the impact of novel ID delivery technologies on human health are fully realized. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Pre-exposure prophylaxis in Peace Corps volunteers with intradermal human diploid cell rabies vaccine.

    PubMed

    Rosa, F W

    1983-04-01

    The Peace Corps has had approximately 60 000 person/years of experience with rabies pre-exposure duck embryo vaccine (DEV) immunizations, which are required in 80% of volunteer assignments. Rabies exposure treatment rate is much higher in these areas than in the United States. One death from rabies has occurred despite pre-exposure injections. One death also occurred from serum hepatitis contracted in local emergency management of an anaphylactic reaction to duck embryo vaccine. A query to the Peace Corps field medical offices obtained reports of 21 serious reactions in approximately 8000 duck embryo immunizations. Two thirds of the reactions occurred with the first injection. Only a third of titres measured after four injections of DEV achieved a protective level of greater than or equal to 1:16. Because of these problems human diploid intracellular vaccine (HDCV) was studied in areas where it was available. Because of the high cost and initial short supply, intradermal injections of 0.1 ml HDCV were given. 567 of 570 persons achieved adequate titres. No systemic reactions were reported with intradermal HDCV.

  5. Intradermal hepatitis B vaccine in thalassaemia and sickle cell disease.

    PubMed Central

    Mok, Q; Underhill, G; Wonke, B; Aldouri, M; Kelsey, M; Jefferies, D

    1989-01-01

    Thirty two patients with beta thalassaemia and sickle cell disease who were having regular blood transfusions were selected to test the efficacy and immunogenicity of low dose (2 micrograms or 0.1 ml) intradermal hepatitis B vaccine compared with the standard (20 micrograms or 1 ml) intramuscular dose. There was no significant difference in the rates of seroconversion, seroconversion had occurred in all patients by seven months. There were no significant differences in antibody titres between the intramuscular and intradermal groups at 1, 2, and 6 months. Although the titres were significantly higher in the intramuscular group at seven months and at 12-18 months, the antibody titre in the intradermal group did not fall below 10 IU/l. The results of this study suggest that low dose intradermal hepatitis B vaccination is an effective and economical way of stimulating an immune response in patients with beta thalassaemia and sickle cell disease. PMID:2526622

  6. Meniscus regeneration by syngeneic, minor mismatched, and major mismatched transplantation of synovial mesenchymal stem cells in a rat model.

    PubMed

    Okuno, Makiko; Muneta, Takeshi; Koga, Hideyuki; Ozeki, Nobutake; Nakagawa, Yusuke; Tsuji, Kunikazu; Yoshiya, Shinichi; Sekiya, Ichiro

    2014-07-01

    We compared the effect of syngeneic and allogeneic transplantation of synovial mesenchymal stem cells (MSCs) for meniscus regeneration in a rat model. Synovium was harvested from the knee joints of three strains of rats. The anterior half of the medial meniscus in both knees of F344 rats was removed and 5 million synovial MSCs derived from F344 (syngeneic transplantation), Lewis (minor mismatched transplantation), and ACI (major mismatched transplantation) were injected into the knee of the F344 rats. At 4 weeks, the area of the regenerated meniscus in the F344 group was significantly larger than that in the ACI group. Histological score was significantly better in the F344 and Lewis groups than in the ACI group at 8 weeks. DiI labeled cells could be observed in the knee joint in the F344 group, but were hardly detected in the ACI group at 1 week. The number of macrophages and CD8 T cells at synovium around the meniscus defect was significantly lower in the F344 group than in the ACI group at 1 week. Syngeneic and minor mismatched transplantation of synovial MSCs promoted meniscus regeneration better than major mismatched transplantation in a rat meniscectmized model.

  7. Kinetics of Innate Immune Response to Yersinia pestis after Intradermal Infection in a Mouse Model

    PubMed Central

    Jarrett, Clayton O.; Gardner, Donald; Hinnebusch, B. Joseph

    2012-01-01

    A hallmark of Yersinia pestis infection is a delayed inflammatory response early in infection. In this study, we use an intradermal model of infection to study early innate immune cell recruitment. Mice were injected intradermally in the ear with wild-type (WT) or attenuated Y. pestis lacking the pYV virulence plasmid (pYV−). The inflammatory responses in ear and draining lymph node samples were evaluated by flow cytometry and immunohistochemistry. As measured by flow cytometry, total neutrophil and macrophage recruitment to the ear in WT-infected mice did not differ from phosphate-buffered saline (PBS) controls or mice infected with pYV−, except for a transient increase in macrophages at 6 h compared to the PBS control. Limited inflammation was apparent even in animals with high bacterial loads (105 to 106 CFU). In addition, activation of inflammatory cells was significantly reduced in WT-infected mice as measured by CD11b and major histocompatibility complex class II (MHC-II) expression. When mice infected with WT were injected 12 h later at the same intradermal site with purified LPS, Y. pestis did not prevent recruitment of neutrophils. However, significant reduction in neutrophil activation remained compared to that of PBS and pYV− controls. Immunohistochemistry revealed qualitative differences in neutrophil recruitment to the skin and draining lymph node, with WT-infected mice producing a diffuse inflammatory response. In contrast, focal sites of neutrophil recruitment were sustained through 48 h postinfection in pYV−-infected mice. Thus, an important feature of Y. pestis infection is reduced activation and organization of inflammatory cells that is at least partially dependent on the pYV virulence plasmid. PMID:22966041

  8. Intradermal Infiltration of Local Anesthetic—Rapid and Bloodless Deepithelialization of the Breast Pedicle

    PubMed Central

    Bennett, Katelyn G.

    2017-01-01

    Summary: Breast reduction is one of the most commonly performed plastic surgery procedures, and pedicle deepithelialization remains a time-consuming step of the operation. This is especially true when using an inferior pedicle. We present a novel technique of intradermal infiltration of the breast pedicle with local anesthetic to facilitate efficient, bloodless deepithelialization. The senior author uses a 20-ml syringe to inject 0.25% lidocaine and 1:400,000 epinephrine just beneath the epidermis of the breast pedicle to create a series of wheals. Approximately 20 ml of local anesthetic is used per pedicle. After injection of local anesthetic, the breast pedicle is deepithelialized in less than 3 minutes. The plane is bloodless, allowing improved visualization secondary to the epinephrine-induced hemostasis. The senior author has had only one case of nipple necrosis in 20 years of experience. Intradermal infiltration of local anesthetic with epinephrine hydrodissects between the epidermis and dermis and provides hemostasis to facilitate rapid deepithelialization. PMID:28280667

  9. Intra-dermal administration of rabies vaccines in developing countries: at an affordable cost.

    PubMed

    Verma, Ramesh; Khanna, Pardeep; Prinja, Shankar; Rajput, Meena

    2011-07-01

    Rabies is a virtually 100% fatal acute viral encephalitis. Rabies occurs in more than 150 countries and territories. Globally there are 17.4 million animal bite cases and more than 55,000 deaths annually. India's 20,000 deaths accounts for 36% of global and 65% of the Asian (31,000) deaths. The Intradermal Rabies Vaccine (IDRV) was first started in Thailand in 1984. In 1992, World Health Organization approved it for use in developing countries which face a shortage of rabies vaccine due to paucity of funds. Vaccines like Purified Vero cell vaccine (PVRV), Purified chick embryo cell vaccine (PCECV) and Human diploid cell vaccine (HDCV) that can be injected by the intradermal route for Post Exposure Prophylaxis as approved by WHO. The regimen approved by the WHO/DCGI India is the Updated Thai Red Cross Regimen, which involves injection of 0.1 mL of reconstituted vaccine per ID site and on two such ID site per visit on Days 0, 3, 7 and 28 (2-2-2-0-2). All reconstituted vaccine unused at the end of 6-8 h must be discarded. The ID route is ideal in terms of economic benefits, safety and efficacy. This reduces the cost of vaccination by about 68%, which is clearly an attractive option for resource-starved countries like India.

  10. Randomized single-blind clinical trial of intradermal methylene blue on pain reduction after open diathermy haemorrhoidectomy.

    PubMed

    Sim, H-L; Tan, K-Y

    2014-08-01

    Open haemorrhoidectomy has been associated with considerable postoperative pain and discomfort. Perianal intradermal injection of methylene blue has been shown to ablate perianal nerve endings and may bring about temporary pain relief after haemorrhoidectomy. We hypothesized that the administration of intradermal methylene blue would reduce postoperative pain during the initial period after surgery. A randomized, prospective, single-blind placebo-controlled trial was conducted. Patients were randomized to intradermal injection at haemorrhoidectomy of either 4 ml 1% methylene blue and 16 ml 0.5% marcaine or of 16 ml 0.5% marcaine and 4 ml saline prior to surgical dissection. Patients were asked to fill in a pain diary with a visual analogue scale. The primary outcome measure was pain score and analgesic use. Secondary outcomes were complications. There were 37 patients in the methylene blue arm and 30 patients in the placebo arm. There were no statistically significant differences in the sex, type of haemorrhoid, number of haemorrhoids excised, duration of surgery or hospital stay. The mean pain scores were significantly lower and the use of paracetamol was also significantly less in the methylene blue group during the first three postoperative days. The risk ratio of acute urinary retention occurring when methylene blue was not used was 2.320 (95% CI 1.754-3.067). Other complication rates were not significantly different. Perianal intradermal injection of methylene blue was useful in reducing the initial postoperative pain of open haemorrhoidectomy. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  11. Pentoxifylline attenuates cytokine stress and Fas system in syngeneic liver proteins induced experimental autoimmune hepatitis.

    PubMed

    Hendawy, Nevien

    2017-08-01

    Apoptosis is a hallmark in the pathogenesis of autoimmune hepatitis (AIH). Cytokine stresses and extrinsic apoptotic pathway have been implicated in this type of hepatic injury. Pentoxifylline plays an important role in controlling inflammation and apoptosis in different autoimmune diseases. To assess the protective effect of pentoxifylline for 30days against pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ) and mediators of extrinsic apoptotic pathway involving TNF receptor 1 (TNFR1) and its ligand TNF-α and Fas receptor and its ligand (FasL) in experimental autoimmune hepatitis (EAH) model. EAH was induced by intraperitoneal injection of syngeneic liver antigen emulsified in complete Freund's adjuvant (CFA) in male C57BL/6 mice. Five groups of mice were used: two control groups; Control PBS group and Control CFA group, EAH group and two EAH+pentoxifylline treated groups in doses (100 or 200mg/kg/d, given by oral gavage). Serum transaminase, pro-inflammatory cytokines (TNF-α and interferon-γ) and hepatic caspase-8 and 3 activities were evaluated. Signs of autoimmune hepatitis were confirmed by liver histology. In addition, hepatic TNFR1, Fas and FasL mRNA expression were assayed. Serum transaminase levels and signs of AIH observed in EAH mice were significantly reduced by pentoxifylline. Upregulated serum TNF-α, IFN-γ, hepatic caspase-8 and 3 activities and TNFR1, Fas and FasL mRNA expression in liver tissues in EAH group were significantly downregulated by pentoxifylline. Pentoxifylline protects against syngeneic liver antigen induced hepatitis and associating apoptosis through attenuating the exaggerated cytokine release and extrinsic apoptotic pathway. Thus, this may represent a new therapeutic strategy for hepatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Cellular Immune Responses Induced with Dose-Sparing Intradermal Administration of HIV Vaccine to HIV-Uninfected Volunteers in the ANRS VAC16 Trial

    PubMed Central

    Launay, Odile; Durier, Christine; Desaint, Corinne; Silbermann, Benjamin; Jackson, Angela; Pialoux, Gilles; Bonnet, Bénédicte; Poizot-Martin, Isabelle; Gonzalez-Canali, Gustavo; Cuzin, Lise; Figuereido, Suzanne; Surenaud, Mathieu; Hamouda, Nadine Ben; Gahery, Hanne; Choppin, Jeannine; Salmon, Dominique; Guérin, Corinne; Villada, Isabelle Bourgault; Guillet, Jean-Gérard

    2007-01-01

    Objective The objective was to compare the safety and cellular immunogenicity of intradermal versus intramuscular immunization with an HIV-lipopeptide candidate vaccine (LIPO-4) in healthy volunteers. Methodology A randomized, open-label trial with 24 weeks of follow-up was conducted in France at six HIV-vaccine trial sites. Sixty-eight healthy 21– to 55–year-old HIV-uninfected subjects were randomized to receive the LIPO-4 vaccine (four HIV lipopeptides linked to a T-helper–stimulating epitope of tetanus-toxin protein) at weeks 0, 4 and 12, either intradermally (0.1 ml, 100 µg of each peptide) or intramuscularly (0.5 ml, 500 µg of each peptide). Comparative safety of both routes was evaluated. CD8+ T-cell immune responses to HIV epitopes (ELISpot interferon-γ assay) and tetanus toxin-specific CD4+ T-cell responses (lymphoproliferation) were assessed at baseline, two weeks after each injection, and at week 24. Results and Conclusion No severe, serious or life-threatening adverse events were observed. Local pain was significantly more frequent after intramuscular injection, but local inflammatory reactions were more frequent after intradermal immunization. At weeks 2, 6, 14 and 24, the respective cumulative percentages of induced CD8+ T-cell responses to at least one HIV peptide were 9, 33, 39 and 52 (intradermal group) or 14, 20, 26 and 37 (intramuscular group), and induced tetanus toxin-specific CD4+ T-cell responses were 6, 27, 33 and 39 (intradermal), or 9, 46, 54 and 63 (intramuscular). In conclusion, intradermal LIPO-4 immunization was well tolerated, required one-fifth of the intramuscular dose, and induced similar HIV-specific CD8+ T-cell responses. Moreover, the immunization route influenced which antigen-specific T-cells (CD4+ or CD8+) were induced. Trial Registration ClinicalTrials.gov NCT00121121 PMID:17712402

  13. Fate of modular cardiac tissue constructs in a syngeneic rat model

    PubMed Central

    Leung, Brendan M; Miyagi, Yasuo; Li, Ren-Ke; Sefton, Michael V

    2014-01-01

    Modular cardiac tissues developed both vascular and cardiac structures in vivo, provided the host response was attenuated by omitting xenoproteins from the modules. Collagen gel modules (with Matrigel™) containing cardiomyocytes (CM) alone or CM with surface seeded endothelial cells (EC; CM/EC modules) were injected into the peri-infarct zone of the heart in syngeneic Lewis rats. After 3 weeks, donor EC developed into blood vessel-like structures that also contained erythrocytes. However, no donor CM were found within the implant sites, presumably because host cells including macrophages and T-cells infiltrated extensively into the injection sites. To lessen the host response, Matrigel™ was omitted from matrix and modules were rinsed with serum-free medium prior to implantation. Host cell infiltration was attenuated, resulting in a higher degree of vascularization with CM/EC modules, than with CM modules without EC. Most importantly, donor CM matured into striated muscle-like structures in Matrigel™-free implants. PMID:23505249

  14. Enhanced growth and experimental metastasis of chemically induced tumor in ultraviolet irradiated syngeneic mice.

    PubMed

    Gensler, H L; Chen, H

    1991-05-01

    Recent studies have shown that ultraviolet (UV) irradiation induces a systemic effect which enhances subsequent tumor induction by benzo[a]pyrene in a manner which is dependent on the dose of benzo[a]pyrene. The present study was designed to test whether UV-B irradiation renders mice susceptible to subcutaneous or intravenous injection of a regressor tumor induced by benzo[a]pyrene. The sources of UV-B irradiation were banks of 6 Westinghouse FS-40 sunlamps, situated 20 cm above the mouse cages. Female BALB/cAnNHsd received five 30-min dorsal UV-B radiation treatments per week for 12 weeks, resulting in a total dose of approx. 6.4 x 10(5) J m-2. Two to seven days after termination of UV treatments, syngeneic regressor tumor cells (BP2) induced by benzo[a]pyrene were injected subcutaneously or intravenously into irradiated mice and unirradiated controls. By 38 days post subcutaneous implantation, 24/30 and 3/30 BP2 implants were detectable in the irradiated and unirradiated mice, respectively. Ultraviolet irradiated mice were also unable to reject lung colonies resulting from intravenous administration of BP2 cells, although they were rejected by unirradiated mice. The mean number of lung colonies per mouse was 16- to 35-fold greater in UV irradiated mice than in unirradiated controls, at 14 to 17 days post injection. Thus, UV irradiation rendered mice, with no known exposure to benzo[a]pyrene, susceptible to a subcutaneous or intravenous injection of a regressor tumor induced by benzo[a]pyrene.

  15. Intracranial AAV-IFN-β gene therapy eliminates invasive xenograft glioblastoma and improves survival in orthotopic syngeneic murine model.

    PubMed

    GuhaSarkar, Dwijit; Neiswender, James; Su, Qin; Gao, Guangping; Sena-Esteves, Miguel

    2017-02-01

    The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard-of-care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon-beta (IFN-β) gene therapy by locally administered adeno-associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models. First, we show that a single intracranial injection of AAV encoding human IFN-β eliminates invasive human GBM8 tumors and promotes long-term survival. Next, we screened five AAV-IFN-β vectors with different promoters to drive safe expression of mouse IFN-β in the brain in the context of syngeneic GL261 tumors. Two AAV-IFN-β vectors were excluded due to safety concerns, but therapeutic studies with the other three vectors showed extensive tumor cell death, activation of microglia surrounding the tumors, and a 56% increase in median survival of the animals treated with AAV/P2-Int-mIFN-β vector. We also assessed the therapeutic effect of combining AAV-IFN-β therapy with temozolomide (TMZ). As TMZ affects DNA replication, an event that is crucial for second-strand DNA synthesis of single-stranded AAV vectors before active transcription, we tested two TMZ treatment regimens. Treatment with TMZ prior to AAV-IFN-β abrogated any benefit from the latter, while the reverse order of treatment doubled the median survival compared to controls. These studies demonstrate the therapeutic potential of intracranial AAV-IFN-β therapy in a highly migratory GBM model as well as in a syngeneic mouse model and that combination with TMZ is likely to enhance its antitumor potency.

  16. Comparison of intradermal and intramuscular delivery followed by in vivo electroporation of SIV Env DNA in macaques

    PubMed Central

    Kulkarni, Viraj; Rosati, Margherita; Bear, Jenifer; Pilkington, Guy R; Jalah, Rashmi; Bergamaschi, Cristina; Singh, Ashish K; Alicea, Candido; Chowdhury, Bhabadeb; Zhang, Gen-Mu; Kim, Eun-Young; Wolinsky, Steven M; Huang, Wensheng; Guan, Yongjun; LaBranche, Celia; Montefiori, David C; Broderick, Kate E; Sardesai, Niranjan Y; Valentin, Antonio; Felber, Barbara K; Pavlakis, George N

    2013-01-01

    A panel of SIVmac251 transmitted Env sequences were tested for expression, function and immunogenicity in mice and macaques. The immunogenicity of a DNA vaccine cocktail expressing SIVmac239 and three transmitted SIVmac251 Env sequences was evaluated upon intradermal or intramuscular injection followed by in vivo electroporation in macaques using sequential vaccination of gp160, gp120 and gp140 expressing DNAs. Both intradermal and intramuscular vaccination regimens using the gp160 expression plasmids induced robust humoral immune responses, which further improved using the gp120 expressing DNAs. The responses showed durability of binding and neutralizing antibody titers and high avidity for > 1 y. The intradermal DNA delivery regimen induced higher cross-reactive responses able to neutralize the heterologous tier 1B-like SIVsmE660_CG7V. Analysis of cellular immune responses showed induction of Env-specific memory responses and cytotoxic granzyme B+ T cells in both vaccine groups, although the magnitude of the responses were ~10x higher in the intramuscular/electroporation group. The cellular responses induced by both regimens were long lasting and could be detected ~1 y after the last vaccination. These data show that both DNA delivery methods are able to induce robust and durable immune responses in macaques. PMID:23811579

  17. Intradermally administered TLR4 agonist GLA-SE enhances the capacity of human skin DCs to activate T cells and promotes emigration of Langerhans cells.

    PubMed

    Schneider, Laura P; Schoonderwoerd, Antoinet J; Moutaftsi, Magdalini; Howard, Randall F; Reed, Steven G; de Jong, Esther C; Teunissen, Marcel B M

    2012-06-13

    The natural TLR4 agonist lipopolysaccharide (LPS) has notable adjuvant activity. However, it is not useful as a vaccine adjuvant due to its toxicity. Glucopyranosyl lipid A (GLA) is a synthetic derivative of the lipid A tail of LPS with limited cytotoxicity, but strong potential to induce immune responses in mice, guinea pigs, non-human primates, and humans. In this study we determined how this synthetic TLR4 agonist affects the function of different subsets of human skin dendritic cells (DCs). The effect of GLA in an aqueous formulation (GLA-AF) or in an oil-in-water emulsion (GLA-SE) was compared to that of LPS and TLR3 agonist poly(I:C) using a human skin explant model with intradermal injections for the administration of the agonists. Intradermal injection of GLA-SE or LPS, but not GLA-AF, enhanced the emigration of CD1a(high)/langerin(+) Langerhans cells (LCs), but not dermal DCs (DDCs). LCs and CD14(-) DDCs exhibited an enhanced mature phenotype following intradermal administration of either of the two GLA formulations tested, similar to DCs that emigrated from LPS-injected skin. However, only injection of GLA-SE resulted in a significant increase in the production of the wide range of cytokines that is observed with LPS. Moreover, DCs that emigrated from GLA-SE-injected skin induced stronger CD4(+) T-cell activation, as indicated by a more pronounced T-cell proliferation, than DCs from skin injected with GLA-AF or LPS. Altogether, our data show that GLA-SE has a notable potency to stimulate the function of skin DCs, indicating that GLA-SE may be a good candidate as adjuvant for vaccines administered via the intradermal route. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Notalgia paresthetica: treatment using intradermal botulinum toxin A.

    PubMed

    Pérez-Pérez, L; García-Gavín, J; Allegue, F; Caeiro, J L; Fabeiro, J M; Zulaica, A

    2014-01-01

    Notalgia paresthetica is a sensory mononeuropathy that affects dorsal segments T2 to T6. It can have a significant effect on quality of life. Numerous treatments have been used with variable results. Five patients diagnosed with notalgia paresthetica were treated with intradermal botulinum toxin A. None had achieved relief of the pruritus with previous treatments. Variable results were observed after the administration of intradermal botulinum toxin. Complete resolution of the pruritus was not achieved in any of the patients. Botulinum toxin A appears to be a safe therapeutic option for patients with notalgia paresthetica. However, data currently available come from small patient series, making it difficult to draw definitive conclusions regarding the true efficacy and long-term effects of this treatment. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

  19. Impact of intradermal abobotulinumtoxinA on facial erythema of rosacea.

    PubMed

    Bloom, Bradley S; Payongayong, Lea; Mourin, Andrea; Goldberg, David J

    2015-01-01

    Facial erythema is a frequent and often distressing complaint of patients with rosacea. Treatment of facial erythema with botulinum toxin has previously been proposed and reported. However, the current literature has mixed results. The primary objective of this study was to evaluate the safety and efficacy of intradermal abobotulinumtoxinA on facial erythema of rosacea. Twenty-five subjects aged 35 to 70 years with Fitzpatrick skin Types I to IV and facial erythema of erythematotelangiectatic rosacea were enrolled in the trial. Subjects received 15 to 45 units of intradermal injections of abobotulinumtoxinA to the nasal tip, nasal bridge, and nasal alae. A nontreating investigator assessed the facial erythema of rosacea using a standardized grading system (0 = absent, 1 = mild erythema, 2 = moderate erythema, and 3 = severe erythema) to evaluate digital photographs at baseline, 1, 2, and 3 months after treatment. Statistical analysis of erythema grade included one-way repeated-measures analysis of variance and pairwise comparisons using SPSS (IBM Corporation) software. Fifteen of the 25 enrolled subjects completed all the appropriate follow-up visits. Only the 15 subjects with complete data were included in analysis. The subjects were of Fitzpatrick skin Types I to III, a mean age of 54 years, and 80% women. The mean baseline erythema grade was 1.80 (±0.56), and the mean erythema grade at 3 months after treatment was 1.00 (±0.38). The treatment resulted in statistically significant improvement in erythema grade at 1, 2, and 3 months after treatment when compared with baseline (p < .05, p < .001, and p < .05, respectively). Pairwise comparison to baseline showed a mean erythema grade improvement of 0.80 (p < .001) at 3-month follow-up. Intradermal injection of botulinum toxin for the treatment of facial erythema of rosacea seems both effective and safe. Larger, randomized, blinded, placebo-controlled studies are warranted. Additionally, further investigation is

  20. Protocol for a double-blind randomised controlled trial of low dose intradermal grass pollen immunotherapy versus a histamine control on symptoms and medication use in adults with seasonal allergic rhinitis (PollenLITE)

    PubMed Central

    2013-01-01

    Background Subcutaneous immunotherapy with high dose grass pollen (typically microgram quantities) was first described over 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. We previously reported that repeated 2-weekly intradermal injections of grass pollen - containing approximately 7 ng of major allergen Phl p 5 – led to a progressive suppression of the allergen-induced cutaneous response, and that by the sixth injection, this was inhibited by over 90%. The purpose of this trial is to investigate the clinical efficacy of intradermal desensitisation with low doses (i.e. nanogram quantities) of grass pollen allergen for seasonal allergic rhinitis. Methods/design The Pollen Low dose Intradermal therapy Evaluation (PollenLITE) is a single centre double-blind randomised parallel group controlled trial of the efficacy and safety of intradermal grass pollen injections plus standard treatment, versus histamine injections plus standard treatment, in adults with moderate-severe grass pollen-induced allergic rhinitis (‘summer hay fever’). A minimum of ninety adults with a history of moderate-severe persistent allergic rhinitis during the UK grass pollen season will be randomised into two equal groups to receive 7 or 8 intradermal injections of grass pollen extract (containing approximately 7 ng of major allergen Phl p 5) or histamine, before the grass pollen season. In the summer, participants will score their symptoms, medication requirements, visual analogue scores, and complete EuroQOL (EQ-5D-5 L) and mini Rhinoconjunctivitis Quality of Life Questionnaires. Global assessments will also be recorded at the end of the pollen season. Blood samples will be collected from all participants for mechanistic immune assays. Skin punch biopsies will also be collected in 40 participants selected at random from intradermal injection sites after the grass pollen season for mechanistic assays. Finally

  1. Intradermal capsaicin inhibits lumbar dorsal horn neuronal responses to colorectal distention.

    PubMed

    Kawasaki, Motohiro; Al-Chaer, Elie D

    2003-05-23

    The purpose of this study was to examine the effect of cutaneous inflammation on the responses of viscerosomatic convergent dorsal horn neurons to graded colorectal distension (CRD) and cutaneous mechanical stimulation. Responses of single viscerosomatic neurons in the lumbar dorsal horn of the rat spinal cord to CRD and to cutaneous stimuli were recorded before and 50 min after cutaneous inflammation induced by intradermal injection of capsaicin in the receptive field (RF) or in the ipsilateral and contralateral forepaw. Capsaicin injection in the RF induced an increase in the spontaneous activity of dorsal horn neurons, an expansion in the size of their RF and facilitated their responses to cutaneous stimuli. An injection placed in the center of the RF attenuated the responses to noxious CRD. Capsaicin injection in the forepaw caused a significant decrease in the responses to CRD but not to cutaneous stimuli. These results indicate that the inhibitory effects, evoked by cutaneous inflammation, can modulate the responses of dorsal horn neurons to CRD, independent of its effect on the responses to cutaneous mechanical stimuli.

  2. Antitumour and antiangiogenic effects of Aplidin in the 5TMM syngeneic models of multiple myeloma.

    PubMed

    Caers, J; Menu, E; De Raeve, H; Lepage, D; Van Valckenborgh, E; Van Camp, B; Alvarez, E; Vanderkerken, K

    2008-06-17

    Aplidin is an antitumour drug, currently undergoing phase II evaluation in different haematological and solid tumours. In this study, we analysed the antimyeloma effects of Aplidin in the syngeneic 5T33MM model, which is representable for the human disease. In vitro, Aplidin inhibited 5T33MMvv DNA synthesis with an IC(50) of 3.87 nM. On cell-cycle progression, the drug induced an arrest in transition from G0/G1 to S phase, while Western blot showed a decreased cyclin D1 and CDK4 expression. Furthermore, Aplidin induced apoptosis by lowering the mitochondrial membrane potential, by inducing cytochrome c release and by activating caspase-9 and caspase-3. For the in vivo experiment, 5T33MM-injected C57Bl/KaLwRij mice were intraperitoneally treated with vehicle or Aplidin (90 microg kg(-1) daily). Chronic treatment with Aplidin was well tolerated and reduced serum paraprotein concentration by 42% (P<0.001), while BM invasion with myeloma cells was decreased by 35% (P<0.001). Aplidin also reduced the myeloma-associated angiogenesis to basal values. This antiangiogenic effect was confirmed in vitro and explained by inhibition of endothelial cell proliferation and vessel formation. These data indicate that Aplidin is well tolerated in vivo and its antitumour and antiangiogenic effects support the use of the drug in multiple myeloma.

  3. Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus

    SciTech Connect

    Steel, Jason C.; Morrison, Brian J.; Mannan, Poonam; Abu-Asab, Mones S.; Wildner, Oliver; Miles, Brian K.; Yim, Kevin C.; Ramanan, Vijay; Prince, Gregory A.; Morris, John C.

    2007-12-05

    Oncolytic adenoviruses as a treatment for cancer have demonstrated limited clinical activity. Contributing to this may be the relevance of preclinical animal models used to study these agents. Syngeneic mouse tumor models are generally non-permissive for adenoviral replication, whereas human tumor xenograft models exhibit attenuated immune responses to the vector. The cotton rat (Sigmodon hispidus) is susceptible to human adenovirus infection, permissive for viral replication and exhibits similar inflammatory pathology to humans with adenovirus replicating in the lungs, respiratory passages and cornea. We evaluated three transplantable tumorigenic cotton rat cell lines, CCRT, LCRT and VCRT as models for the study of oncolytic adenoviruses. All three cells lines were readily infected with adenovirus type-5-based vectors and exhibited high levels of transgene expression. The cell lines supported viral replication demonstrated by the induction of cytopathogenic effect (CPE) in tissue culture, increase in virus particle numbers and assembly of virions seen on transmission electron microscopy. In vivo, LCRT and VCRT tumors demonstrated delayed growth after injection with replicating adenovirus. No in vivo antitumor activity was seen in CCRT tumors despite in vitro oncolysis. Adenovirus was also rapidly cleared from the CCRT tumors compared to LCRT and VCRT tumors. The effect observed with the different cotton rat tumor cell lines mimics the variable results of human clinical trials highlighting the potential relevance of this model for assessing the activity and toxicity of oncolytic adenoviruses.

  4. Significant antitumor effect of a synthetic lipid A analogue, DT-5461, on murine syngeneic tumor models.

    PubMed

    Kumazawa, E; Tohgo, A; Soga, T; Kusama, T; Osada, Y

    1992-01-01

    The antitumor effect of a synthetic lipid A analogue, DT-5461, was investigated using syngeneic tumor models in mice. Intravenous injection of DT-5461 into mice transplanted with solid tumors of MethA fibrosarcoma, MH134 hepatoma, MM46 mammary carcinoma, Lewis lung carcinoma (3LL), and colon adenocarcinomas 26 and 38 resulted in significant reductions in the weight of all tumors except Colon 26, with marked hemorrhagic necrosis of tumor tissues. Efficacy was almost equal to that of an Escherichia coli-type synthetic lipid A (compound 506), and also to those of some chemotherapeutics including Adriamycin, mitomycin C, fluorouracil and cisplatin. Furthermore, DT-5461 was more effective than other immunotherapeutics, including picibanil (OK-432) and lentinan. However, its antitumor effects were inferior to those of Adriamycin or OK-432 against the malignant ascites caused by intraperitoneal inoculation with MethA or with MH134 cells; life span was not prolonged by either intraperitoneal or intravenous administration. In addition, although DT-5461 showed direct inhibitory effects on the in vitro growth of MethA or MH134, these were much weaker than those of Adriamycin. These findings clearly indicated that DT-5461 with systemic administration is a highly effective antitumor agent on solid tumors, and suggest that the antitumor effect of DT-5461 with potent necrotizing activity might derive from indirect mechanisms related to the activation of host immune systems and not to the weak direct cytotoxicity.

  5. Postinflammation stage of autoimmune orchitis induced by immunization with syngeneic testicular germ cells alone in mice.

    PubMed

    Naito, Munekazu; Hirai, Shuichi; Terayama, Hayato; Qu, Ning; Kuerban, Maimaiti; Musha, Muhetaerjiang; Kitaoka, Miyuki; Ogawa, Yuki; Itoh, Masahiro

    2012-12-01

    We previously established an immunological infertility model, experimental autoimmune orchitis (EAO), which can be induced by two subcutaneous injections of viable syngeneic testicular germ cells on days 0 and 14 in mice without using any adjuvant. In this EAO model, CD4+ T-cell-dependent lymphocytic infiltration and immune deposits were found with spermatogenic disturbance on day 120. However, the late stage of EAO (= postactive inflammation stage on day 365) has not yet been investigated. Therefore, we investigated the histopathological characteristics of the late stage. The results revealed that the lymphocytic infiltration finally resolved; however, the seminiferous epithelium persistently showed maturation arrest and the Sertoli cell-only feature. In the seminiferous tubules showing maturation arrest, both proliferation and apoptosis of germ cells had occurred simultaneously. It was also noted that there were deposits of immunoglobulin G and the third component of complement on the thickened basement membrane of seminiferous tubules in the late stage of EAO. These results indicate that histopathology after active inflammation in EAO comprises persistent damage to the seminiferous epithelium and may resemble the histopathology of "idiopathic disturbance of spermatogenesis" in man.

  6. Establishment of a syngeneic orthotopic model of prostate cancer in immunocompetent rats

    PubMed Central

    Suzuki, Shugo; Naiki-Ito, Aya; Kuno, Toshiya; Punfa, Wanisa; Long, Ne; Kato, Hiroyuki; Inaguma, Shingo; Komiya, Masami; Shirai, Tomoyuki; Takahashi, Satoru

    2014-01-01

    We previously established 3 cell lines (PLS10, PLS20 and PLS30) from a chemically-induced prostate carcinoma in F344 rats, and demonstrated high potential for metastasis in nude mice. In the present study, we investigated the feasibility of establishing an orthotopic model using the 3 rat prostate cancer cell lines in immunocompetent rats with the aim of resolving species-mismatch problems and defects of immune systems. The PLS10, PLS20 and PLS30 cell lines were injected into the ventral prostates of 6-week-old rats, which were then sacrificed at experimental weeks 4 and 8. Tumor mass formation was found in rats with PLS10, but not in those with PLS20 or PLS30. Additionally, metastatic carcinomas could be detected in lymph nodes and lungs of PLS10-inoculated rats. Genetic analysis demonstrated K-ras gene mutations in PLS10 and PLS20, but not in PLS30 cells. There were no mutations in p53 and KLF6. In conclusion, we established a syngeneic orthotopic model for prostate cancer in immunocompetent rats simulating human castration-resistant prostate cancer (CRPC), which should prove useful for development and validation of therapeutic agents, especially with immunotherapy. PMID:26023257

  7. Transplantation of syngeneic transfected cells to probe the in vivo immune response to viral proteins

    SciTech Connect

    Nakayama, Hiroyuki; Shibata, Motohiro; Wohlenberg, C.; Rooney, J.F.; Notkins, A.L. )

    1991-01-01

    BALB/3T3 cells were transfected with the glycoprotein D (gD) gene of herpes simplex virus (HSV) and a cell line expressing gD on the cell surface was isolated. In vitro, {sup 51}Cr release tests showed that the transfected cells were destroyed by anti-HSV antibody in the presence of complement. To investigate in vivo immune response, the gD-transfected cells were transplanted into the footpads of syngeneic HSV-immunized or unimmunized BALB/c mice. In unimmunized mice, transfected cells remained intact for 7 days or longer, and the site of injection showed only slight lymphocyte infiltration. In contrast, in immunized mice, transfected cells elicited massive lymphocyte infiltration and were mostly destroyed by day 4. Analysis of infiltrating cells revealed that they were mainly Thy1{sup +} and CD8{sup +} lymphocytes along with small numbers of CD5{sup +}, CD4{sup +}, and B lymphocytes. These studies show that transfected murine cells expressing gD can be used to study the in vivo immune response to single viral proteins and they argue that the immune response contributes to the pathogenesis of HSV infection.

  8. IMMUNE AND NATURAL ANTIBODIES TO SYNGENEIC MURINE PLASMA CELL TUMORS

    PubMed Central

    Herberman, Ronald B.; Aoki, Tadao

    1972-01-01

    Cytotoxic antibody to a plasma cell tumor antigen was produced in syngeneic BALB mice by immunization with viable or inactivated plasma cell tumors. Antibody with the same specificity was found in the sera of normal BALB and other strains of mice. This natural antibody reacted with an antigen with characteristics indistinguishable from the previously described alloantigen, PC.1, and with viral envelope antigen, χVEA. The incidence of cytotoxic reactivity and the antibody titers reached a peak in normal BALB mice at 3–4 months of age, and were lower in 9–12-month old mice. The sera of germfree mice had lower reactivity; but when the mice were transferred to conventional conditions, their sera soon became as active as those of conventional mice. A virus common to all plasma cell tumors, which is present in latent form in some normal tissues of BALB and other PC.1 positive strains, is suggested as the cause for the PC.1 antigen and for the appearance of natural antibody to it. The considerable evidence for the close association of a virus with plasma cell tumors is presented. PMID:5033423

  9. Tannic acid raises survival rate of mice bearing syngeneic tumors.

    PubMed

    Koide, T; Kamei, H; Hashimoto, Y; Kojima, T; Hasegawa, M

    1999-06-01

    Tannic acid which was found earlier to have growth suppressive activity against cultured tumor cells, was given to Balb/c mice p.o. The mice had been inoculated with syngeneic tumor cells (Meth/A) i.p. When tannic acid was suspended in drinking water and given daily at doses of approximately 875 mg/kg/day and 1750 mg/kg/day, the respective survival rates were 59% and 48%, with that of the control mice being 29%. To study the cytotoxicity of tannic acid, we administered the tannic acid to mice at 875 and 1750 mg/kg/day for 35 days. The weight gain for each dose was lower than that of the control, although the difference was not significant. When tannic acid was given at 8750 mg/kg/day, the weight gain was significantly lower than the control. A histologic study did not show any pathological findings in the kidney, liver, or lungs in the mice given tannic acid at the above doses.

  10. Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses.

    PubMed Central

    Raz, E; Carson, D A; Parker, S E; Parr, T B; Abai, A M; Aichinger, G; Gromkowski, S H; Singh, M; Lew, D; Yankauckas, M A

    1994-01-01

    The skin and mucous membranes are the anatomical sites were most viruses are first encountered by the immune system. Previous experiments have suggested that striated muscle cells are unique among mammalian cell types in their capacity to take up and express free DNA in the absence of a viral vector or physical carrier. However, we have found that mice injected into the superficial skin with free (naked) plasmid DNA encoding the influenza nucleoprotein gene had discrete foci of epidermal and dermal cells, including cells with dendritic morphology, that contained immunoreactive nucleoprotein antigen. A single intradermal administration of 0.3-15 micrograms of free plasmid DNA induced anti-nucleoprotein-specific antibody and cytotoxic T lymphocytes that persisted for at least 68-70 weeks after vaccination. Intradermal gene administration induced higher antibody titers than did direct gene injection into skeletal muscle and did not cause local inflammation or necrosis. Compared with control animals, the gene-injected mice were resistant to challenge with a heterologous strain of influenza virus. These results indicate that the cells of the skin can take up and express free foreign DNA and induce cellular and humoral immune responses against the encoded protein. We suggest that DNA uptake by the skin-associated lymphoid tissues may play a role in the induction of cytotoxic T cells against viruses and other intracellular pathogens. Images PMID:7937799

  11. A pilot randomized study to assess immunogenicity, reactogenicity, safety and tolerability of two human papillomavirus vaccines administered intramuscularly and intradermally to females aged 18-26 years.

    PubMed

    Nelson, E Anthony S; Lam, Hugh Simon; Choi, Kai C; Ho, Wendy C S; Fung, L W Eva; Cheng, Frankie W T; Sung, Rita Y T; Royals, Michael; Chan, Paul K S

    2013-07-25

    Intradermal administration of human papillomavirus (HPV) vaccines could be dose-sparing and cost-saving. This pilot randomized study assessed Cervarix(®) and Gardasil(®) administered either intramuscularly or intradermally, in different doses (full-dose or reduced to 20%) by different methods (needle and syringe or PharmaJet needle-free jet injection device). Following an initial reactogenicity study of 10 male subjects, sexually naïve women aged 18-26 years were randomized to the eight study groups to receive vaccine at 0, 2 and 6 months. 42 female subjects were enrolled and complete data were available for 40 subjects. Intradermal administration of either vaccine raised no safety concerns but was more reactogenic than intramuscular administration, although still tolerable. All subjects demonstrated a seroconversion (titre≥1:320) by Day 95. Further evaluation of intradermal HPV vaccination and its potential for cost reduction in resource poor settings is warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Tolerability of intramuscular and intradermal delivery by CELLECTRA® adaptive constant current electroporation device in healthy volunteers

    PubMed Central

    Diehl, Malissa C; Lee, Jessica C; Daniels, Stephen E; Tebas, Pablo; Khan, Amir S; Giffear, Mary; Sardesai, Niranjan Y; Bagarazzi, Mark L

    2013-01-01

    DNA vaccines are being developed as a potentially safe and effective immunization platform. However, translation of DNA vaccines into a clinical setting has produced results that have fallen short of those generated in a preclinical setting. Various strategies are being developed to address this lack of potency, including improvements in delivery methods. Electroporation (EP) creates transient increases in cell membrane permeability, thus enhancing DNA uptake and leading to a more robust immune response. Here, we report on the safety and tolerability of delivering sterile saline via intramuscular (IM) or intradermal (ID) injection followed by in vivo electroporation using the CELLECTRA® adaptive constant current device in healthy adults from two open-label studies. Pain, as assessed by VAS, was highest immediately after EP but diminishes by about 50% within 5 min. Mean VAS scores appear to correlate with the amount of energy delivered and depth of needle insertion, especially for intramuscular EP. Mean scores did not exceed 7 out of 10 or 3 out of 10 for IM and ID EP, respectively. The majority of adverse events included mild to moderate injection site reactions that resolved within one day. No deaths or serious adverse events were reported during the course of either study. Overall, injection followed by EP with the CELLECTRA® device was well-tolerated and no significant safety concerns were identified. These studies support the further development of electroporation as a vaccine delivery method to enhance immunogenicity, particularly for diseases in which traditional vaccination approaches are ineffective. PMID:24051434

  13. Regulatory Serotype Mutations in TETRAHYMENA PYRIFORMIS, Syngen 1

    PubMed Central

    Doerder, F. P.

    1973-01-01

    A method utilizing allelic exclusion has been developed to isolate mutants of Tetrahymena pyriformis, syngen 1, in which the normal pattern of expression of mutally exclusive surface antigens is altered. Cells homozygous for the recessive mutant allele R-1r do not express the L, H and T serotypes when grown under conditions appropriate for their expression. Rather, a new immobilization antigen, r, is expressed. Cells homozygous for the recessive mutant allele R-3r also express the r antigen instead of H serotypes, but are normal in their expression of T antigens. Genetic analyses show that R-1 and R-3 are not closely linked, that R-1 is linked to T by 9.3 units, and that R-3 may be loosely linked to the mt locus. Different linkage values were obtained, however, when different inbred laboratory strains were used, suggesting the possible existence of crossover modifying genes. The rates of assortment of R-1R/R-1r and R-3R/R-3r heterozygotes into pure sublines expressing either H or r serotypes are close to the values observed for the differentiation of heterozygotes at other loci. The data confirm the previous observation that genetic coupling relationships are not maintained in macronuclear phenotypes and are consistent with the hypothesis that the macronucleus contains 45 assorting subunits. The assortment of the double heterozygote R-1R/R-1r, R-3R/R-3r at Rf=0.0112 suggests that the units of assortment are not individual genetic loci or chromosome fragments, but that the units may be complete genomes. PMID:17248612

  14. SynGenics Optimization System (SynOptSys)

    NASA Technical Reports Server (NTRS)

    Ventresca, Carol; McMilan, Michelle L.; Globus, Stephanie

    2013-01-01

    The SynGenics Optimization System (SynOptSys) software application optimizes a product with respect to multiple, competing criteria using statistical Design of Experiments, Response-Surface Methodology, and the Desirability Optimization Methodology. The user is not required to be skilled in the underlying math; thus, SynOptSys can help designers and product developers overcome the barriers that prevent them from using powerful techniques to develop better pro ducts in a less costly manner. SynOpt-Sys is applicable to the design of any product or process with multiple criteria to meet, and at least two factors that influence achievement of those criteria. The user begins with a selected solution principle or system concept and a set of criteria that needs to be satisfied. The criteria may be expressed in terms of documented desirements or defined responses that the future system needs to achieve. Documented desirements can be imported into SynOptSys or created and documented directly within SynOptSys. Subsequent steps include identifying factors, specifying model order for each response, designing the experiment, running the experiment and gathering the data, analyzing the results, and determining the specifications for the optimized system. The user may also enter textual information as the project progresses. Data is easily edited within SynOptSys, and the software design enables full traceability within any step in the process, and facilitates reporting as needed. SynOptSys is unique in the way responses are defined and the nuances of the goodness associated with changes in response values for each of the responses of interest. The Desirability Optimization Methodology provides the basis of this novel feature. Moreover, this is a complete, guided design and optimization process tool with embedded math that can remain invisible to the user. It is not a standalone statistical program; it is a design and optimization system.

  15. Simplification of intradermal skin testing in Hymenoptera venom allergic children.

    PubMed

    Cichocka-Jarosz, Ewa; Stobiecki, Marcin; Brzyski, Piotr; Rogatko, Iwona; Nittner-Marszalska, Marita; Sztefko, Krystyna; Czarnobilska, Ewa; Lis, Grzegorz; Nowak-Węgrzyn, Anna

    2017-03-01

    The direct comparison between children and adults with Hymenoptera venom anaphylaxis (HVA) has never been extensively reported. Severe HVA with IgE-documented mechanism is the recommendation for venom immunotherapy, regardless of age. To determine the differences in the basic diagnostic profile between children and adults with severe HVA and its practical implications. We reviewed the medical records of 91 children and 121 adults. Bee venom allergy was exposure dependent, regardless of age (P < .001). Atopy was more common in children (P = .01), whereas cardiovascular comorbidities were present almost exclusively in adults (P = .001). In the bee venom allergic group, specific IgE levels were significantly higher in children (29.5 kUA/L; interquartile range, 11.30-66.30 kUA/L) compared with adults (5.10 kUA/L; interquartile range, 2.03-8.30 kUA/L) (P < .001). Specific IgE levels for culprit insect venom were higher in bee venom allergic children compared with the wasp venom allergic children (P < .001). In adults, intradermal tests revealed higher sensitivity, accompanied by larger area of skin reactions, regardless of type of venom. At concentrations lower than 0.1 μg/mL, 16% of wasp venom allergic children and 39% of bee venom allergic children had positive intradermal test results. The median tryptase level was significantly higher in adults than in children for the entire study group (P = .002), as well as in bee (P = .002) and wasp venom allergic groups (P = .049). The basic diagnostic profile in severe HVA reactors is age dependent. Lower skin test reactivity to culprit venom in children may have practical application in starting the intradermal test procedure with higher venom concentrations. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum Sporozoites in Controlled Human Malaria Infection

    PubMed Central

    Lyke, Kirsten E.; Laurens, Matthew B.; Strauss, Kathy; Adams, Matthew; Billingsley, Peter F.; James, Eric; Manoj, Anita; Chakravarty, Sumana; Plowe, Christopher V.; Li, Ming Lin; Ruben, Adam; Edelman, Robert; Green, Michael; Dube, Tina J.; Kim Lee Sim, B.; Hoffman, Stephen L.

    2015-01-01

    Controlled human malaria infection (CHMI) is a powerful tool to evaluate malaria vaccine and prophylactic drug efficacy. Until recently CHMI was only carried out by the bite of infected mosquitoes. A parenteral method of CHMI would standardize Plasmodium falciparum sporozoite (PfSPZ) administration, eliminate the need for expensive challenge facility infrastructure, and allow for use of many P. falciparum strains. Recently, intradermal (ID) injection of aseptic, purified, cryopreserved PfSPZ was shown to induce P. falciparum malaria; however, 100% infection rates were not achieved by ID injection. To optimize ID PfSPZ dosing so as to achieve 100% infection, 30 adults aged 18–45 years were randomized to one of six groups composed of five volunteers each. The parameters of dose (1 × 104 versus 5 × 104 PfSPZ total dose per volunteer), number of injections (two versus eight), and aliquot volume per ID injection (10 μL versus 50 μL) were studied. Three groups attained 100% infection: 1 × 104 PfSPZ in 50 μL/2 doses, 1 × 104 PfSPZ in 10 μL/2 doses, and 5 × 104 PfSPZ in 10 μL/8 doses. The group that received 5 × 104 PfSPZ total dose in eight 10 μL injections had a 100% infection rate and the shortest prepatent period (mean of 12.7 days), approaching the prepatent period for the current CHMI standard of five infected mosquitoes. PMID:26416102

  17. Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum Sporozoites in Controlled Human Malaria Infection.

    PubMed

    Lyke, Kirsten E; Laurens, Matthew B; Strauss, Kathy; Adams, Matthew; Billingsley, Peter F; James, Eric; Manoj, Anita; Chakravarty, Sumana; Plowe, Christopher V; Li, Ming Lin; Ruben, Adam; Edelman, Robert; Green, Michael; Dube, Tina J; Sim, B Kim Lee; Hoffman, Stephen L

    2015-12-01

    Controlled human malaria infection (CHMI) is a powerful tool to evaluate malaria vaccine and prophylactic drug efficacy. Until recently CHMI was only carried out by the bite of infected mosquitoes. A parenteral method of CHMI would standardize Plasmodium falciparum sporozoite (PfSPZ) administration, eliminate the need for expensive challenge facility infrastructure, and allow for use of many P. falciparum strains. Recently, intradermal (ID) injection of aseptic, purified, cryopreserved PfSPZ was shown to induce P. falciparum malaria; however, 100% infection rates were not achieved by ID injection. To optimize ID PfSPZ dosing so as to achieve 100% infection, 30 adults aged 18-45 years were randomized to one of six groups composed of five volunteers each. The parameters of dose (1 × 10(4) versus 5 × 10(4) PfSPZ total dose per volunteer), number of injections (two versus eight), and aliquot volume per ID injection (10 μL versus 50 μL) were studied. Three groups attained 100% infection: 1 × 10(4) PfSPZ in 50 μL/2 doses, 1 × 10(4) PfSPZ in 10 μL/2 doses, and 5 × 10(4) PfSPZ in 10 μL/8 doses. The group that received 5 × 10(4) PfSPZ total dose in eight 10 μL injections had a 100% infection rate and the shortest prepatent period (mean of 12.7 days), approaching the prepatent period for the current CHMI standard of five infected mosquitoes.

  18. Regulation of immune responses in SJL and F1 hybrid mice by gamma-irradiated syngeneic lymphoma cells

    SciTech Connect

    Katz, I.R.; Nagase, F.; Bell, M.K.; Ponzio, N.M.; Thorbecke, G.J.

    1984-01-01

    Syngeneic mixed lymphocyte-stimulating la+ lymphomas of SJL mice (reticulum cell sarcoma(s) (RCS)) were found to modulate immune responses in vivo. Simultaneous injection of 2 X 10(7) gamma-irradiated or glutaraldehyde-fixed RCS cells with the antigen sheep red blood cells (SRBC) or 2,4,6-trinitrophenol (TNP)-Ficoll markedly suppressed the subsequent plaque-forming cell response in the spleen. The suppression of the anti-SRBC response was prevented by pretreatment of the mice with cyclophosphamide, whereas the suppression of the anti-TNP-Ficoll response was not affected. RCS injection induced high interferon serum titers within 24 hours after injection, which were not prevented by pretreatment with cyclophosphamide. Injection of gamma-irradiated RCS cells (gamma-RCS) or RCS cell extract 2 days prior to antigen enhanced the anti-SRBC but markedly suppressed the anti- TNP-Ficoll response. Injection of RCS both on day -2 and day 0 enhanced the anti-SRBC response. SJL mice 8-9 months of age showed much less or no suppression when gamma-RCS cells were injected on day 0. Certain F1 hybrids of SJL also showed the gamma-RCS-induced suppression of the anti-SRBC response. Suppression was seen in SJL X BALB.B but not in SJL X BALB/c mice and in SJL X A.TH but not in SJL X A.TL mice, suggesting an I-region effect. F1 hybrids of SJL by B10 background mice showed no significant suppression. Enhancement of the anti-SRBC response by prior injection of gamma-RCS was seen in all F1 hybrid mice examined.

  19. Immunization against strontium-90 induction of bone tumors with inactivated FBJ virus and irradiated syngeneic strontium-90-induced tumor cells

    SciTech Connect

    Reif, A.E.; Triest, W.E.

    1981-01-01

    Three hundred six C57BL/6J female mice were subdivided into a control group left untreated and an experimental group treated intraperitoneally with 1.0 ..mu..Ci strontium-90/g of body weight at an age of 66 days. Treatments for the groups were as follows: none, 6 injections of formalin-inactivated FBJ viral preparation, 6 injections of active FBJ viral preparation, and 2 injections of 10,000 rad irradiated transplantable osteosarcoma previously induced in C57BL/6J mice by strontium-90. In addition to the above groups, two other groups were treated with respectively 0.032 and 0.10 ..mu..Ci strontium-90/g body weight in order to obtain information on the dose-response relationship between the injection of strontium-90 and the yield of bone tumors. In the groups not treated with strontium-90, only 1 bone tumor developed; this occurred in the group injected with FBJ virus. The incidence of bone tumors in the groups treated with 1.0 ..mu..Ci strontium-90 was significantly lower (18.5% or 18.2%) in the two groups that had received injections of inactivated FBJ virus or irradiated isogenic osteosarcoma when compared to the group left uninjected, which developed 43.5% tumors. In contrast, the strontium-90-treated group that also received injections of active FBJ virus developed 63.0% tumors. Only a single bone tumor developed in the groups treated solely with intermediate doses of strontium-90. The results indicate that immunization with inactivated FBJ virus or with irradiated syngeneic strontium-90-induced tumor cells can significantly decrease the development of strontium-90-induced tumors.

  20. Successful radioimmunotherapy of established syngeneic rat colon carcinoma with 211At-mAb

    PubMed Central

    2013-01-01

    Background Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with α-emitting radionuclides such as astatine-211 (211At). Radioimmunotherapy utilizing α-particle emitting radionuclides is considered especially suitable for the treatment of small cell clusters and single cells, although lesions of different sizes may also be present in the patient. The aim of this study was primarily to evaluate the toxicity and secondarily in vivo efficacy of a 211At-labeled monoclonal antibody (mAb) directed against colon carcinoma with tumor diameters of approximately 10 mm. Methods Eighteen rats with subperitoneal syngeneic colon carcinoma were allocated to three groups of six animals together with three healthy rats in each group. The groups were injected intravenously with either 150 μg of unlabeled mAbs (controls) or 2.5 or 5 MBq 211At-mAbs directed towards the Lewis Y antigen expressed on the cell membrane of several carcinomas. Tumor volume, body weight, and blood cell counts were monitored for 100 days after treatment. Results Local tumors were non-palpable in five out of six rats after treatment with both activities of 211At-mAbs, compared to one out of six in the control group. At the study end, half of the animals in each group given 211At-BR96 and one animal in the control group were free from disease. Radioimmunotherapy resulted in dose-dependent, transient weight loss and myelotoxicity. Survival was significantly better in the groups receiving targeted alpha therapy than in those receiving unlabeled mAbs. Conclusions This study demonstrates the possibility of treating small, solid colon carcinoma tumors with α-emitting radionuclides such as 211At bound to mAbs, with tolerable toxicity. PMID:23557183

  1. Quantifying spontaneous metastasis in a syngeneic mouse melanoma model using real time PCR.

    PubMed

    Deng, Wentao; McLaughlin, Sarah L; Klinke, David J

    2017-08-07

    Modeling metastasis in vivo with animals is a priority for both revealing mechanisms of tumor dissemination and developing therapeutic methods. While conventional intravenous injection of tumor cells provides an efficient and consistent system for studying tumor cell extravasation and colonization, studying spontaneous metastasis derived from orthotopic tumor sites has the advantage of modeling more aspects of the metastatic cascade, but is challenging as it is difficult to detect small numbers of metastatic cells. In this work, we developed an approach for quantifying spontaneous metastasis in the syngeneic mouse B16 system using real time PCR. We first transduced B16 cells with lentivirus expressing firefly luciferase Luc2 gene for bioluminescence imaging. Next, we developed a real time quantitative PCR (qPCR) method for the detection of luciferase-expressing, metastatic tumor cells in mouse lungs and other organs. To illustrate the approach, we quantified lung metastasis in both spontaneous and experimental scenarios using B16F0 and B16F10 cells in C57BL/6Ncrl and NOD-Scid Gamma (NSG) mice. We tracked B16 melanoma metastasis with both bioluminescence imaging and qPCR, which were found to be self-consistent. Using this assay, we can quantitatively detect one Luc2 positive tumor cell out of 10(4) tissue cells, which corresponds to a metastatic burden of 1.8 × 10(4) metastatic cells per whole mouse lung. More importantly, the qPCR method was at least a factor of 10 more sensitive in detecting metastatic cell dissemination and should be combined with bioluminescence imaging as a high-resolution, end-point method for final metastatic cell quantitation. Given the rapid growth of primary tumors in many mouse models, assays with improved sensitivity can provide better insight into biological mechanisms that underpin tumor metastasis.

  2. [Studies on the intradermal reactions with the fractions of Ascaris lumbricoides

    PubMed

    Lee, Chan Wook

    1967-06-01

    and kept in 30 degrees C incubator for 24 hours. Among of them, the active one was seleted and put to sudden freeze at -70 degrees C for 20 hours. the whole body was powdered in a dried condition and kept it in ampoule at -4 degrees C. a) Crude antigen: The ether extract of powdered Ascaris lumbrucoides were motared by adding veronal buffer solution (1:100) and kept in icebox for 48 hours. The suspension was diluted with veronal buffer solution in the ratio of 1:10,000. b) Protein antigen : This antigen was prepared by Chaffee's modified methods and ammonium sulfate extraction mehtod. c) Polysaccharide antigen: Chaffee's modified method and ethanol extration method were applied. d) Mixed antigen : The same amount of preparation of protein and polysaccharide antigen were mixed. C. Intrdermal test 1. The intradermal test : 0.02ml of natigen was injected on the anterior surface of the frearm in human and on the back in aninmal, with tuberculin syringe. The criteria of the skin reaction were determined as follows; wheal: -; 0-4mm, +/-; 5-7mm, +;8-9mm, +; 21-32mm, ++; 33-44mm, +++; 45-56mm, ++++; over 57mm, in diameter. D. Stool examination : All the stool examination was done by formalin-ether concectration(M.G.L) method. E.P.G (egg per gram) was also determined by Stoll's egg counting method. RESULT : The intradermal reaction after the injection of each antigen was observed at 15, 30, 60 minutes and 3, 24 hours. In 58 ascariasis cases, the peak of wheal was appeared at 30 minute; 93.0% with the crude antigen, 15.5% with the mixed antigen, 10.3% with the Protein antigen, but all were negative in the polysaccharide antigen. The erythema reaction paralledled, in general, to the wheal; 75.8% at 15 minutes, 72.5% at 30 minutes and 48.3% at 60 mintues, with the crude antigen. Only 3.4% showed erythema at 15,30, and 60 minutes int the case of mixed antigen, and 1.7% fo positive was appeared at 30 minutes in the case of protein antigen, but none was observed in the

  3. Low levels of allogeneic but not syngeneic hematopoietic chimerism reverse autoimmune insulitis in prediabetic NOD mice.

    PubMed

    Kaminitz, Ayelet; Mizrahi, Keren; Yaniv, Isaac; Farkas, Daniel L; Stein, Jerry; Askenasy, Nadir

    2009-09-01

    The relative efficiencies of allogeneic and syngeneic bone marrow transplantation and the threshold levels of donor chimerism required to control autoimmune insulitis were evaluated in prediabetic NOD mice. Male and female NOD mice were conditioned by radiation and grafted with bone marrow cells from allogeneic and syngeneic sex-mismatched donors. Establishment of full allogeneic chimerism in peripheral blood reversed insulitis and restored glucose tolerance despite persistence of residual host immune cells. By contrast, sublethal total body irradiation (with or without syngeneic transplant) reduced the incidence and delayed the onset of diabetes. The latter pattern was also seen in mice that rejected the bone marrow allografts. Low levels of stable allogeneic hematopoietic chimerism (>1%) were sufficient to prevent the evolution of diabetes following allogeneic transplantation. The data indicate that immunomodulation attained at low levels of allogeneic, but not syngeneic, hematopoietic chimerism is effective in resolution of islet inflammation at even relatively late stages in the evolution of the prediabetic state in a preclinical model. However, our data question the efficacy and rationale behind syngeneic (autologous-like) immuno-hematopoietic reconstitution in type 1 diabetes.

  4. Intradermal testing of horses with and without insect bite hypersensitivity in The Netherlands using an extract of native Culicoides species.

    PubMed

    Sloet van Oldruitenborgh-Oosterbaan, Marianne M; van Poppel, Miriam; de Raat, Inge J; van den Boom, Robin; Savelkoul, Huub F J

    2009-10-01

    Intradermal tests using a Culicoides nubeculosus extract have proven unreliable for diagnosis of equine insect bite hypersensitivity (IBH) in the Netherlands. The aim of this study was to evaluate the diagnostic value of an extract derived from the Dutch species C. obsoletus and C. pulicaris. Thirteen pairs of horses were tested, each pair consisting of one horse with IBH and the other a healthy control. Each horse was injected intradermally with 0.1 mL of three concentrations of Culicoides whole body extract (1 : 1000 w/v, 1 : 10,000 w/v and 1 : 25,000 w/v), histamine solution (0.01 mg/mL, positive control) and phosphate-buffered saline (negative control). Skin responses were evaluated after 30 min and at 1, 4 and 24 h. At all time points the absolute wheal diameter elicited by Culicoides extract 1 : 1000 w/v was significantly larger (P < 0.01) in the IBH horses than in the control horses. Using the 1 : 10,000 w/v extract the difference was significant at 1, 4 and 24 h and using the 1 : 25,000 w/v extract only at 24 h. The relative wheal diameter was greater in IBH than in control horses at all concentrations and time points except at 0.5 h for the 1 : 10,000 w/v and 1 : 25,000 w/v concentrations. At the 1 : 1000 w/v concentration, the sensitivity and specificity was 92% using the relative wheal diameter. These results indicate that intradermal testing using 1 : 1000 w/v concentration Culicoides extracts relevant to the locality provides useful support for a clinical diagnosis of equine insect hypersensitivity.

  5. HER2/neu DNA vaccination by intradermal gene delivery in a mouse tumor model: Gene gun is superior to jet injector in inducing CTL responses and protective immunity.

    PubMed

    Nguyen-Hoai, Tam; Kobelt, Dennis; Hohn, Oliver; Vu, Minh D; Schlag, Peter M; Dörken, Bernd; Norley, Steven; Lipp, Martin; Walther, Wolfgang; Pezzutto, Antonio; Westermann, Jörg

    2012-12-01

    DNA vaccines are potential tools for the induction of immune responses against both infectious disease and cancer. The dermal application of DNA vaccines is of particular interest since the epidermal and dermal layers of the skin are characterized by an abundance of antigen-presenting cells (APCs). The aim of our study was to compare tumor protection as obtained by two different methods of intradermal DNA delivery (gene gun and jet injector) in a well-established HER2/neu mouse tumor model. BALB/c mice were immunized twice with a HER2/neu-coding plasmid by gene gun or jet injector. Mice were then subcutaneously challenged with HER2/neu(+) syngeneic D2F2/E2 tumor cells. Protection against subsequent challenges with tumor cells as well as humoral and T-cell immune responses induced by the vaccine were monitored. Gene gun immunization was far superior to jet injector both in terms of tumor protection and induction of HER2/neu-specific immune responses. After gene gun immunization, 60% of the mice remained tumor-free until day 140 as compared with 25% after jet injector immunization. Furthermore, gene gun vaccination was able to induce both a strong T(H)1-polarized T-cell response with detectable cytotoxic T-lymphocyte (CTL) activity and a humoral immune response against HER2/neu, whereas the jet injector was not. Although the disadvantages that were associated with the use of the jet injector in our model may be overcome with methodological modifications and/or in larger animals, which exhibit a thicker skin and/or subcutaneous muscle tissue, we conclude that gene gun delivery constitutes the method of choice for intradermal DNA delivery in preclinical mouse models and possibly also for the clinical development of DNA-based vaccines.

  6. Direct evidence for a stem cell common to hematopoiesis and its in vitro microenvironment: studies on syngeneic (inbred) Wistar Furth rats

    SciTech Connect

    Islam, A.; Gong, J.K.; Henderson, E.S.

    1988-01-01

    When injected into a group of lethally irradiated syngeneic (inbred) Wistar Furth (WF) rats, suspensions of stromal cells grown in monolayer culture from the marrow of WF rats produced hemopoietic colonies in the spleen and rescued 50% of the rats, while 90% of the non-injected (control) rats died within 30 days and had no hemopoietic colonies in the spleens. Fifty percent of the injected (test) rats which died between days 6 and 22 showed hemopoietic regeneration in the bone marrow, while little or no evidence of hemopoietic regeneration was seen in the control animals. Our results suggest that the marrow stroma grown in vitro contain cells with hemopoietic potential and are transplantable.

  7. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing

    PubMed Central

    Schmidt, Barbara A.; Horsley, Valerie

    2013-01-01

    Acute wound healing in the skin involves the communication of multiple cell types to coordinate keratinocyte and fibroblast proliferation and migration for epidermal and dermal repair. Many studies have focused on the interplay between hematopoietic cells, keratinocytes and fibroblasts during skin wound healing, yet the possible roles for other cell types within the skin, such as intradermal adipocytes, have not been investigated during this process. Here, we identify that adipocyte lineage cells are activated and function during acute skin wound healing. We find that adipocyte precursor cells proliferate and mature adipocytes repopulate skin wounds following inflammation and in parallel with fibroblast migration. Functional analysis of mice with defects in adipogenesis demonstrates that adipocytes are necessary for fibroblast recruitment and dermal reconstruction. These data implicate adipocytes as a key component of the intercellular communication that mediates fibroblast function during skin wound healing. PMID:23482487

  8. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing.

    PubMed

    Schmidt, Barbara A; Horsley, Valerie

    2013-04-01

    Acute wound healing in the skin involves the communication of multiple cell types to coordinate keratinocyte and fibroblast proliferation and migration for epidermal and dermal repair. Many studies have focused on the interplay between hematopoietic cells, keratinocytes and fibroblasts during skin wound healing, yet the possible roles for other cell types within the skin, such as intradermal adipocytes, have not been investigated during this process. Here, we identify that adipocyte lineage cells are activated and function during acute skin wound healing. We find that adipocyte precursor cells proliferate and mature adipocytes repopulate skin wounds following inflammation and in parallel with fibroblast migration. Functional analysis of mice with defects in adipogenesis demonstrates that adipocytes are necessary for fibroblast recruitment and dermal reconstruction. These data implicate adipocytes as a key component of the intercellular communication that mediates fibroblast function during skin wound healing.

  9. Photodynamic therapy controls of Staphylococcus aureus intradermal infection in mice.

    PubMed

    Almeida, Palloma Porto; Pereira, Ítalo Sousa; Rodrigues, Karine Bitencourt; Leal, Lorena Santos; Marques, Andressa Souza; Rosa, Luciano Pereira; da Silva, Francine Cristina; da Silva, Robson Amaro Augusto

    2017-08-01

    Infections caused by Staphylococcus aureus lead to skin infections, as well as soft tissues and bone infections. Given the communal resistance to antibiotics developed by strains of this bacterium, photodynamic therapy emerges as a promising alternative treatment to control and cure infections. Females of the Balb/C mice were infected with 10(8) CFU of methicillin-resistant S. aureus (MRSA) and divided into four distinct groups: P-L- (negative control group), P+L- (group exposed only to curcumin), P-L+ (group exposed only to LED incidence of 450 nm, 75 mW/cm(2), and 54 J/cm(2) for 10 min), and P+L+ (group exposed to curcumin followed by 10 min of LED irradiation) (n = 24). The mice were euthanized 48 and 72 h after infection, and biologic materials were collected for analysis of the bacterial load, peripheral blood leukocyte counts, and draining lymph nodes cell counts. The normalization of data was checked and the ANOVA test was applied. The bacterial load in the draining lymph node of P+L+ group was lower when compared to the control groups 72 h post infection (p < 0.0001), indicating that the LED incidence associated with curcumin controls of the staphylococci intradermal infection. The number of the total lymph node cells shows to be lower than control groups in the two availed times (p < 0.01). The histological analysis and the counting of white blood cells did not show differences among cells in the blood and in the tissue of infection. This is the first report showing that photodynamic therapy may be effective against MRSA infection in a murine model of intradermal infection.

  10. DNA vaccine coding for the rhesus prostate specific antigen delivered by intradermal electroporation in patients with relapsed prostate cancer.

    PubMed

    Eriksson, Fredrik; Tötterman, Thomas; Maltais, Anna-Karin; Pisa, Pavel; Yachnin, Jeffrey

    2013-08-20

    We tested safety, clinical efficacy and immunogenicity of a DNA vaccine coding for rhesus prostate specific antigen (PSA) delivered by intradermal injection and skin electroporation. Fifteen patients with biochemical relapse of prostate cancer without macroscopic disease participated in this phase I study. Patients were started on a 1 month course of androgen deprivation therapy (ADT) prior to treatment. Vaccine doses ranged from 50 to 1,600 μg. Study subjects received five vaccinations at four week intervals. All patients have had at least one year of follow-up. No systemic toxicity was observed. Discomfort from electroporation did not require analgesia or topical anesthetic. No clinically significant changes in PSA kinetics were observed as all patients required antiandrogen therapy shortly after completion of the 5 months of vaccination due to rising PSA. Immunogenicity, as measured by T-cell reactivity to the modified PSA peptide and to a mix of overlapping PSA peptides representing the full length protein, was observed in some patients. All but one patient had pre-study PSA specific T-cell reactivity. ADT alone resulted in increases in T-cell reactivity in most patients. Intradermal vaccination with skin electroporation is easily performed with only minor discomfort for the patient. Patients with biochemical relapse of prostate cancer are a good model for testing immune therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Inhibition of B16 melanoma growth and metastasis in C57BL mice by vaccination with a syngeneic endothelial cell line

    PubMed Central

    Yoshiura, Kenta; Nishishita, Toshihide; Nakaoka, Takashi; Yamashita, Naohide; Yamashita, Naomi

    2009-01-01

    Background Key role of angiogenesis in tumor growth and metastasis based on accumulating evidence and recent progress of immunotherapy have led us to investigate vaccine therapy targeting tumor angiogenesis. Methods C57BL/6J mice were vaccinated with a syngeneic endothelial cell line Tpit/E by subcutaneous injection once a week. Prior to ninth vaccination, the mice were challenged with B16/F10 melanoma cells by subcutaneous inoculation on the back for the tumor growth model or by tail venous injection for the lung metastasis model. Development of subcutaneous tumor and lung metastasis was monitored by computed tomography scanning, which enabled accurate evaluation with the minimized sacrifice of mice. Results Vaccination with Tpit/E cells inhibited subcutaneous tumor growth and appearance of lung metastasis compared to control. Survival period was elongated in the Tpit/E vaccination in both of the two models. We also obtained hybridomas secreting specific antibodies to Tpit/E cells from a mouse vaccinated with the cells, indicating that specific immune response to the syngeneic endothelial cells was elicited. Conclusion These results suggest that vaccination with an autologous endothelial cell line may be effective against melanoma. PMID:19183492

  12. Intra-amniotic delivery of amniotic-derived neural stem cells in a syngeneic model of spina bifida.

    PubMed

    Turner, Christopher G; Pennington, Elliot C; Gray, Fabienne L; Ahmed, Azra; Teng, Yang D; Fauza, Dario O

    2013-01-01

    Neural stem cells (NSCs) may promote spinal cord repair in fetuses with experimental spina bifida. We sought to determine the fate of amniotic-derived NSCs (aNSCs) after simple intra-amniotic injection in a syngeneic model of spina bifida. Fetal neural tube defects were induced on 20 pregnant Lewis dams by prenatal administration of retinoic acid. Ten dams served as amniotic fluid donors for epigenetic isolation of aNSCs, which were expanded and labeled with 5-bromo-2'-deoxyuridine. The remaining 10 dams received intra-amniotic injections of the processed aNSCs, blindly in all their fetuses (n = 37) on gestational day 17 (term = E21-22). Fetuses with spina bifida underwent screening for the presence of donor aNSCs in the spinal cord at term. Donor cells were identified in 93.3% of the animals with spina bifida, selectively populating the neural placode, typically in clusters, retaining an undifferentiated morphology, and predominantly on exposed neural surfaces, though some were detected deeper in neighboring neural tissue. The amniotic cavity can serve as a route of administration of NSCs in experimental spina bifida. Simple intra-amniotic delivery of NSCs may be a practical adjuvant to regenerative strategies for the treatment of spina bifida. Copyright © 2013 S. Karger AG, Basel.

  13. Correction of midface volume deficiency using hyaluronic acid filler and intradermal radiofrequency.

    PubMed

    Ko, Eun Jung; Kim, Hyuk; Park, Won-Seok; Kim, Beom Joon

    2015-02-01

    Hyaluronic acid (HA) fillers are increasingly used for midface augmentation, which can be performed for facial rejuvenation. Previous study proved that radiofrequency (RF) treatment prior to HA filler injection may provide synergistic and long-lasting effects for the reduction of nasolabial fold wrinkles. Here, we report a case in which the efficacy of two different treatments using RF and HA filler and HA filler alone was assessed using a split-face design. In conclusion, the intradermal needle RF with HA filler may be a more safe and effective method than HA filler alone for correcting midface volume deficit. Appropriate volume loss replacement should correct the flattening and furrowing of the central area of the mid-cheek, which is a consequence of the aging process. Also, it will provide a more youthful appearance. Hyaluronic acid (HA) fillers are an established intervention for correcting facial volume deficiency. In a previous study ( 1 ), radiofrequency (RF) was used to overcome the short duration of HA fillers and resulted in a good outcome.

  14. Effects of intradermally administered plasmid deoxyribonucleic acid on ovine popliteal lymph node morphology.

    PubMed

    Uwiera, R R; Rankin, R; Adams, G P; Pontarollo, R; van Drunen Littel-van den Hurk, S; Middleton, D M; Babiuk, L A; Griebel, P J

    2001-02-01

    In the last decade it has become apparent that bacterial deoxyribonucleic acid (DNA) is recognized as a "danger signal" by the mammalian immune system. To investigate this interaction, sheep were injected intradermally two centimeters distal to the lateral prominence of the fibular head with 400 microg of purified plasmid DNA. Over a 28-day period ultrasound measurements indicated a progressive increase in size of both plasmid and saline (controls) treated popliteal lymph nodes and at Day 30 macroscopic and histological measurements of the lymph nodes were determined. Compared with the contralateral control lymph nodes, plasmid exposed lymph nodes were heavier (2.8 +/- 0.1g vs. 2.0 +/- 0.6 g) and displayed prominent histological changes in the cortex and medulla. Average medullary cord thickness (114.2 +/- 25.2 microm) and the average distance across medullary sinuses (64.4 +/- 2.5 microm) were significantly greater after plasmid exposure relative to contralateral controls (62.7 +/- 14.9 microm and 36.5 +/- 1.0 microm, respectively). Total number of germinal centers (71.4 +/- 17.7) and the total area of germinal centers (4.0 +/- 1.3 mm(2)) within the cortex of popliteal lymph nodes exposed to plasmid were also significantly greater than the controls (40.4 +/- 11.4 and 1.6 +/- 0.5 mm(2), respectively). Our results demonstrate that a single exposure to plasmid DNA has long term effects on regional lymph node weight and morphology.

  15. Syngeneic AAV Pseudo-particles Potentiate Gene Transduction of AAV Vectors.

    PubMed

    Wang, Qizhao; Dong, Biao; Pokiniewski, Katie A; Firrman, Jenni; Wu, Zhongren; Chin, Mario P S; Chen, Xiongwen; Liu, LinShu; Xu, Ruian; Diao, Yong; Xiao, Weidong

    2017-03-17

    Adeno-associated virus (AAV) vectors have emerged as a safe and efficient gene therapy platform. One complication is that a significant amount of empty particles have always been generated as impurities during AAV vector production. However, the effects of such particles on AAV vector performance remain unclear. Here we systemically evaluated the biological properties of three types of "empty" AAV particles: syngeneic pseudo-vectors with partial AAV genomes derived from DNA of the corresponding full particles, allogeneic pseudo-vectors with partial genomes different from the corresponding full particles, and null pseudo-vectors with no DNA inside the capsids. The syngeneic particles in excess increased the corresponding full AAV vector transgene expression both in vivo and in vitro. However, such effects were not observed with null or allogeneic particles. The observed differences among these pseudo-AAV particles may be ascribed to the syngeneic pseudo-vector DNA facilitating the complementary DNA synthesis of the corresponding full AAV particles. Our study suggests that the DNA content in the pseudo-vectors plays a key role in dictating their effects on AAV transduction. The effects of residual "empty" particles should be adequately assessed when comparing AAV vector performance. The syngeneic AAV pseudo-vectors may be used to enhance the efficacy of gene therapy.

  16. Resistance to oncolytic myxoma virus therapy in nf1(-/-)/trp53(-/-) syngeneic mouse glioma models is independent of anti-viral type-I interferon.

    PubMed

    Zemp, Franz J; McKenzie, Brienne A; Lun, Xueqing; Maxwell, Lori; Reilly, Karlyne M; McFadden, Grant; Yong, V Wee; Forsyth, Peter A

    2013-01-01

    Despite promising preclinical studies, oncolytic viral therapy for malignant gliomas has resulted in variable, but underwhelming results in clinical evaluations. Of concern are the low levels of tumour infection and viral replication within the tumour. This discrepancy between the laboratory and the clinic could result from the disparity of xenograft versus syngeneic models in determining in vivo viral infection, replication and treatment efficacy. Here we describe a panel of primary mouse glioma lines derived from Nf1 (+/-) Trp53 (+/-) mice in the C57Bl/6J background for use in the preclinical testing of the oncolytic virus Myxoma (MYXV). These lines show a range of susceptibility to MYXV replication in vitro, but all succumb to viral-mediated cell death. Two of these lines orthotopically grafted produced aggressive gliomas. Intracranial injection of MYXV failed to result in sustained viral replication or treatment efficacy, with minimal tumour infection that was completely resolved by 7 days post-infection. We hypothesized that the stromal production of Type-I interferons (IFNα/β) could explain the resistance seen in these models; however, we found that neither the cell lines in vitro nor the tumours in vivo produce any IFNα/β in response to MYXV infection. To confirm IFNα/β did not play a role in this resistance, we ablated the ability of tumours to respond to IFNα/β via IRF9 knockdown, and generated identical results. Our studies demonstrate that these syngeneic cell lines are relevant preclinical models for testing experimental glioma treatments, and show that IFNα/β is not responsible for the MYXV treatment resistance seen in syngeneic glioma models.

  17. Induction of CD8+ cytotoxic T lymphocytes by immunization with syngeneic irradiated HIV-1 envelope derived peptide-pulsed dendritic cells.

    PubMed

    Takahashi, H; Nakagawa, Y; Yokomuro, K; Berzofsky, J A

    1993-08-01

    Based on the evidence that CD8+ cytotoxic T cells (CTL) precursors do not appear to distinguish between virus-infected cells and viral peptide-pulsed syngeneic cells, we have developed methods for priming class I MHC molecule restricted CD8+ CTL with such peptides without using any adjuvant. We were able to prime in vivo such CTL immunity lasting at least 6 months with a single i.v. injection of syngeneic 2200-3300 rad irradiated peptide-pulsed spleen cells, and even more efficiently with a very small number of irradiated class II MHC molecule expressing splenic dendritic cells (DC). No foreign serum source was necessary during the pulsing. Interestingly, we could not generate significant CTL activity with unirradiated or low dose (< 1100 rad) irradiated spleen cells. Because even purified DC required irradiation for optimal activity, because unirradiated B cells did not significantly inhibit the immunization with DC, and because B cell depletion did not substitute for irradiation, we believe that the effect of irradiation is more to determine homing of the cells than to eliminate interference by B cells. Intravenous immunization was much more effective than s.c. or i.p. immunization. CTL generated by this method could kill both peptide-pulsed syngeneic targets and targets endogenously expressing the whole gp160 gene. Moreover, we found that we could prime CD8+ CTL with the minimal 10-residue core peptide (RGPGRAFVTI) for optimal presentation by class I MHC molecules as efficiently as the original p18. These results suggested that DC bearing antigenic peptide may prime antigen-specific CD8+ CTL in vivo. These results offer useful information for development of synthetic peptide vaccines and immunotherapy.

  18. Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

    PubMed Central

    Gutierrez-Mecinas, Maria; Polgár, Erika; Todd, Andrew J

    2016-01-01

    Background Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway. PMID:27270268

  19. Antibody response of patients after postexposure rabies vaccination with small intradermal doses of purified chick embryo cell vaccine or purified Vero cell rabies vaccine.

    PubMed Central

    Briggs, D. J.; Banzhoff, A.; Nicolay, U.; Sirikwin, S.; Dumavibhat, B.; Tongswas, S.; Wasi, C.

    2000-01-01

    Although the introduction of tissue culture vaccines for rabies has dramatically improved the immunogenicity and safety of rabies vaccines, they are often prohibitively expensive for developing countries. To examine whether smaller doses of these vaccines could be used, we tested the safety and immunogenicity of purified chick embryo cell vaccine (PCECV) on 211 patients in Thailand with World Health Organization (WHO) category II and III exposures to rabies. The patients presented at two Thai hospitals and were randomized into three groups. Patients in Group 1 received 0.1 ml PCECV intradermally at two sites on days 0, 3, 7, and at one site on days 30 and 90. Group 2 was treated similarly, except that purified Vero cell rabies vaccine (PVRV) was used instead of PCECV. Group 3 received 1.0 ml PCECV intramuscularly on days 0, 3, 7, 14, 30 and 90. After 0, 3, 7, 14, 30 and 90 days serum was collected from the subjects and the geometric mean titres (GMTs) of rabies virus neutralizing antibody determined. After 14 days the GMT of 59 patients vaccinated intradermally with PCECV was equivalent to that of patients who received PVRV. Adverse reactions were more frequent in patients who received vaccines intradermally, indicating the reactions were associated with the route of injection, rather than the vaccine per se. We conclude that PCECV is a safe and highly immunogenic vaccine for postexposure rabies vaccination when administered intradermally in 0.1-ml doses using the two-site method ("2,2,2,0,1,1") recommended by WHO. PMID:10859864

  20. Sequential immunogene therapy with interleukin-12- and interleukin-15-engineered neuroblastoma cells cures metastatic disease in syngeneic mice.

    PubMed

    Croce, Michela; Meazza, Raffaella; Orengo, Anna Maria; Radić, Luana; De Giovanni, Barbara; Gambini, Claudio; Carlini, Barbara; Pistoia, Vito; Mortara, Lorenzo; Accolla, Roberto S; Corrias, Maria Valeria; Ferrini, Silvano

    2005-01-15

    To investigate the potential synergistic effects of Neuro2a neuroblastoma cells engineered with IL-12 and/or IL-15 genes in improving survival of syngeneic mice bearing neuroblastoma metastatic disease. Neuro2a cells engineered with interleukin (IL)-12 (Neuro2a/IL-12), IL-15 (Neuro2a/IL-15), or both cytokines (Neuro2a/IL-12/IL-15) were injected s.c. in syngeneic A/J mice challenged i.v. with Neuro2a parental cells (Neuro2apc) using different schedules of administration in either preventive or therapeutic settings. A single injection of Neuro2a/IL-12 or Neuro2a/IL-15 cells induced resistance to a subsequent i.v. Neuro2apc challenge in 45% and 28% of mice, respectively. Neuro2a/IL-12/IL-15 cells protected 28% of mice, showing no synergistic effect. However, sequential vaccination with Neuro2a/IL-12 (day -30) followed by Neuro2a/IL-15 (day -15) protected 71% of mice from subsequent challenge with Neuro2apc. A single dose of Neuro2a/IL-12 prolonged the mean survival time of mice bearing established metastatic neuroblastoma from 21 +/- 3 to 46 +/- 27 days but failed to cure mice, whereas Neuro2a/IL-15 or Neuro2a/IL-12/IL-15 were ineffective. However, sequential vaccination with Neuro2a/IL-12 (day +3) followed by Neuro2a/IL-15 (day +13) cured 43% of mice as assessed by histologic analysis of different organs from long-term surviving mice. CTL activity against Neuro2apc cells was observed in splenocytes from treated mice, and CD8(+) T-cell depletion abrogated the therapeutic effect of vaccination. Sequential vaccination with IL-12- and IL-15-engineered neuroblastoma cells induced optimal preventive and therapeutic effects, which may be related to the Th1 priming effect of IL-12 followed by the enhancement of CD8(+) T-cell responses and their maintenance mediated by IL-15.

  1. Antitumor activity of epigenetic immunomodulation combined with CTLA-4 blockade in syngeneic mouse models

    PubMed Central

    Covre, A; Coral, S; Nicolay, H; Parisi, G; Fazio, C; Colizzi, F; Fratta, E; Di Giacomo, A M; Sigalotti, L; Natali, P G; Maio, M

    2015-01-01

    The multifaceted immunomodulatory activity of DNA hypomethylating agents improves immunogenicity and immune recognition of neoplastic cells; thus, we predicted they could be utilized to design new immunotherapeutic combinations in cancer. Testing this hypothesis, the antitumor efficacy of the DNA hypomethylating agent 5-aza-2′-deoxycytidine (5-AZA-CdR) combined with the anti-CTLA-4 monoclonal antibody (mAb) 9H10 in syngeneic transplantable murine models was investigated. Murine mammary carcinoma TS/A or mesothelioma AB1 cells were injected in BALB/c, athymic nude, and SCID/Beige mice that were treated with 5-AZA-CdR, mAb 9H10, or their combination. Tumor volumes were captured at different time-points; molecular and immunohistochemical assays investigated changes in neoplastic and normal tissues. A significant antitumor effect of 5-AZA-CdR combined with mAb 9H10 was found: compared to controls, a 77% (p < 0.01), 54% (p < 0.01) and 33% (p = 0.2) decrease in TS/A tumor growth was induced by 5-AZA-CdR combined with mAb 9H10, 5-AZA-CdR or mAb 9H10, respectively. These antitumor activities were confirmed utilizing the AB1 model. 5-AZA-CdR-based regimens induced a promoter-demethylation-sustained tumor expression of cancer testis antigens. MHC class I expression was up-regulated by 5-AZA-CdR. Antitumor efficacy of 5-AZA-CdR in athymic nude and SCID/Beige mice was not increased by mAb 9H10. In BALB/c mice, combined treatment induced the highest tumor infiltration by CD3+ lymphocytes, which included both CD8+ and CD4+ T cells; no such infiltrates were observed in normal tissues. This significant immune-related antitumor activity of 5-AZA-CdR combined with CTLA-4 blockade, demonstrated in highly aggressive mouse tumor models, provides a strong scientific rationale to implement epigenetically-based immunotherapies in cancer patients. PMID:26405573

  2. Experimental study of the mixed (oral-intradermal) vaccination method in enteric diseases.

    PubMed

    Dimache, G; Croitoru, M; Dimache, A

    1996-01-01

    Enteric vaccines are currently administered in man either orally or parenterally, each vaccination route having its advantages and disadvantages. In an attempt to cumulate the favourable effects of the two immunization methods a combined (oral-intradermal) anti-S.typhimurium and anti-S.typhi vaccination scheme was applied in mice. For comparison reasons, the oral (one or two immunization cycles) and the parenteral (one or two vaccine doses intradermally administered) vaccinations were used. The results obtained showed that mixed (oral-intradermal) vaccination induces a higher protective effect to infection with S.typhimurium or S.typhi, as compared to the single oral vaccination (one or two cycles) and a protective effect which does not differ from that obtained by intradermal vaccination.

  3. Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse.

    PubMed

    Akiyama, T; Nagamine, M; Davoodi, A; Iodi Carstens, M; Cevikbas, F; Steinhoff, M; Carstens, E

    2015-10-01

    Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml(-1)·min(-1)), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans.

  4. Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse

    PubMed Central

    Akiyama, T.; Nagamine, M.; Davoodi, A.; Iodi Carstens, M.; Cevikbas, F.; Steinhoff, M.

    2015-01-01

    Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml−1·min−1), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans. PMID:26311187

  5. Targeting Skin Dendritic Cells to Improve Intradermal Vaccination

    PubMed Central

    Romani, N.; Flacher, V.; Tripp, C. H.; Sparber, F.; Ebner, S.; Stoitzner, P.

    2014-01-01

    Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigen-presenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin+), dermal langerinneg, and dermal langerin+ dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerinneg dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14+ dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge. PMID:21253784

  6. Lipopolysaccharide contamination in intradermal DNA vaccination: toxic impurity or adjuvant?

    PubMed

    van den Berg, Joost H; Quaak, Susanne G L; Beijnen, Jos H; Hennink, Wim E; Storm, Gert; Schumacher, Ton N; Haanen, John B A G; Nuijen, Bastiaan

    2010-05-05

    Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Mice were vaccinated with a model DNA vaccine (Luc-NP) with an increasing content of residual LPS. The effect of LPS on systemic toxicity, antigen expression and cellular immunity was studied. The presence of LPS in the DNA vaccine neither induced systemic toxicity (as reflected by IL-6 concentration in serum), nor influenced antigen expression (measured by intravital imaging). Higher LPS contents however, appeared to be associated with an elevated cytotoxic T-lymphocyte (CTL) response but without reaching statistical significance. Interestingly, the DNA tattoo procedure by itself was shown to induce a serum cytokine response that was at least as potent as that induced by parenteral LPS administration. LPS does not show toxicity in mice vaccinated by DNA tattooing at dose levels well above those encountered in GMP-grade DNA preparations. Thus, residual LPS levels in the pharmaceutical range are not expected to adversely affect clinical outcome of vaccination trials and may in fact have some beneficial adjuvant effect. The observed pro-inflammatory effects of DNA tattoo may help explain the high immunogenicity of this procedure. Copyright 2009 Elsevier B.V. All rights reserved.

  7. Utility of intradermal blood smear in the detection of asymptomatic malaria parasitaemia in pregnancy.

    PubMed

    Okusanya, B O; Eigbefoh, J O; Ohiosimuan, O; Isabu, P A; Okpere, E E; Inyang, N J

    2009-09-01

    We evaluated the usefulness of intradermal smear microscopy (IDS) in the detection of asymptomatic malaria parasitaemia in pregnancy. Peripheral venous blood (PVB) served as control. The preference for the collection technique of dermal blood was also assessed. One hundred and fifty (150) asymptomatic women were recruited. They had both intradermal smear and peripheral venous blood smear were made for all patients. Measures of test validity included sensitivity, specificity and accuracy rate. Test of statistical significance was with Yates correlation at 95% confidence limit. The prevalence of asymptomatic malaria parasitaemia was higher using intradermal smear (35.3% vs 33.3%) though this was not statistically significant. Intradermal smear had a sensitivity of 40% and specificity of 67%. The positive predictive value was 37.8% with accuracy rate of 58%. 41% of participants preferred the technique of collection of intradermal blood. Intradermal smear appears to have no usefulness in the detection of asymptomatic malaria parasitaemia in pregnancy. However, we recommend more studies on its value in pregnancy, especially amongst symptomatic pregnant women.

  8. Efficacy of intradermal mesotherapy in cellulite reduction - Conventional and high-frequency ultrasound monitoring results.

    PubMed

    Sylwia, Malinowska; Krzysztof, Mlosek Robert

    2017-10-01

    Cellulite affects the majority of women and is an unacceptable cosmetic defect. Therefore, effective methods for cellulite reduction are being sought. Intradermal mesotherapy is one of such methods. The aim of the study was to assess the efficacy of intradermal mesotherapy in cellulite reduction, using conventional and high-frequency ultrasound. Twenty-one women with cellulite underwent a series of intradermal mesotherapy procedures. The following parameters were assessed: thickness of epidermis, dermis and hypodermis, echogenicity of dermis and the surface area of serrated hypodermis-dermis junction. Furthermore, the thigh circumference was measured; body mass index and cellulite severity were assessed based on photographs using Nürnberger-Müller's scale. Intradermal mesotherapy reduced severity of cellulite. The surface area of serrated hypodermis-dermis junction and hypodermis thickness decreased significantly as compared to baseline. Cellulite reduction was also confirmed by palpation, decreased thigh circumference and the Nürnberger-Müller's grade. There were no statistically significant changes in epidermis or dermis thickness, body weight and the BMI. Intradermal mesotherapy offers effective cellulite reduction. It is a simple and safe treatment, which makes it popular. Further research in mesotherapy is essential due to a limited number of published studies. Ultrasound is a useful method to monitor intradermal mesotherapy and assess its efficacy.

  9. Identification of Paramecium bursaria syngens through molecular markers--comparative analysis of three loci in the nuclear and mitochondrial DNA.

    PubMed

    Greczek-Stachura, Magdalena; Potekhin, Alexey; Przyboś, Ewa; Rautian, Maria; Skoblo, Inna; Tarcz, Sebastian

    2012-09-01

    This is the first attempt to resolve the phylogenetic relationship between different syngens of Paramecium bursaria and to investigate at a molecular level the intraspecific differentiation of strains originating from very distant geographical locations. Herein we introduce a new collection of five P. bursaria syngens maintained at St Petersburg State University, as the international collection of syngens was lost in the 1960s. To analyze the degree of speciation within Paramecium bursaria, we examined 26 strains belonging to five different syngens from distant and geographically isolated localities using rDNA (ITS1-5.8S-ITS2-5'LSU) fragments, mitochondrial cytochrome c oxidase subunit I (COI), and H4 gene fragments. It was shown that P. bursaria strains of the same syngens cluster together in all three inferred molecular phylogenies. The genetic diversity among the studied P. bursaria strains based on rDNA sequences was rather low. The COI divergence of Paramecium bursaria was also definitely lower than that observed in the Paramecium aurelia complex. The nucleotide sequences of the H4 gene analyzed in the present study indicate the extent of genetic differences between the syngens of Paramecium bursaria. Our study demonstrates the diagnostic value of molecular markers, which are important tools in the identification of Paramecium bursaria syngens. Copyright © 2011 Elsevier GmbH. All rights reserved.

  10. Attenuation of TGF-β signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model

    PubMed Central

    Biswas, Tanuka; Gu, Xiang; Yang, Junhua; Ellies, Lesley G; Sun, Lu-Zhe

    2014-01-01

    Previous studies have suggested that TGF-β functions as a tumor promoter in metastatic, mesenchymal-like breast cancer cells and that TGF-β inhibitors can effectively abrogate tumor progression in several of these models. Here we report a novel observation with the use of genetic and pharmacological approaches, and murine mammary cell injection models in both syngeneic and immune compromised mice. We found that TGF-β receptor II (TβRII) knockdown in the MMTV-PyMT derived Py8119, a mesenchymal-like murine mammary tumor cell line, resulted in increased orthotopic tumor growth potential in a syngeneic background and a similar trend in an immune compromised background. Systemic treatment with a small-molecule TGF-β receptor I kinase inhibitor induced a trend towards increased metastatic colonization of distant organs following intra cardiac inoculation of Py8119 cells, with little effect on the colonization of luminal-like Py230 cells, also derived from MMTV-PyMT tumors. Taken together, our data suggest that the attenuation of TGF-β signaling in mesenchymal-like mammary tumors does not necessarily inhibit their malignant potential, and anti-TGF-β therapeutic intervention requires greater precision in identifying molecular markers in tumors with an indication of functional TGF-β signaling. PMID:24368187

  11. Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells

    PubMed Central

    1987-01-01

    We have developed a model of syngeneic adoptive transfer for type I diabetes mellitus of NOD mice. This model consists in injecting spleen cells from diabetic adult mice into newborn NOD recipients. 50% of recipients inoculated with 20 X 10(6) cells develop diabetes within the first 10 wk of life, at a time when none of the control littermates have yet become diabetic. The earliest successful transfers are observed at 3 wk of age, at a time when controls do not even exhibit histological changes in their pancreas. In addition we have shown that: (a) both males and females can be adoptively transferred, despite the fact that males rarely develop spontaneous diabetes in our colony; (b) diabetes transfer is a dose-dependent phenomenon that provides an in vivo assay for comparing the autoimmune potential of spleen cells from mice at various stages of their natural history; (c) the susceptibility of the recipients to the transfer is limited in time and declines after 3 wk; and (d) both L3T4+ and Lyt-2+ T cell subsets are necessary for the successful transfer. The neonatal syngeneic transfer provides an effective model for studies of the cellular events involved at regulatory and effector stages of autoimmune type I diabetes. PMID:3309126

  12. Fluzone® intra-dermal (Intanza®/Istivac® Intra-dermal): An updated overview.

    PubMed

    Bragazzi, Nicola Luigi; Orsi, Andrea; Ansaldi, Filippo; Gasparini, Roberto; Icardi, Giancarlo

    2016-10-02

    Influenza is a highly contagious respiratory acute viral disease which imposes a very heavy burden both in terms of epidemiology and costs, in the developed countries as well as in the developing ones. It represents a serious public health concern and vaccination constitutes an important tool to reduce or at least mitigate its burden. Despite the existence of a broad armamentarium against influenza and despite all the efforts and recommendations of international organisms to broaden immunization, influenza vaccination coverage is still far from being optimal. This, taken together with logistic and technical difficulties that can result into vaccine shortage, makes intra-dermal (ID) vaccines, such as Fluzone® ID and Intanza®, particularly attractive. ID vaccines are comparable and, in some cases, superior to intra-muscular/sub-cutaneous vaccines in terms of immunogenicity, safety, reactogenicity, tolerability and cross-protection profiles, as well as in terms of patient preference, acceptance and vaccine selection. Further advances, such as Fluzone® ID with alternative B strains and Quadrivalent Fluzone® ID or the possibility of self-administering the vaccines, make influenza ID vaccines even more valuable.

  13. Antitumour and antiangiogenic effects of Aplidin® in the 5TMM syngeneic models of multiple myeloma

    PubMed Central

    Caers, J; Menu, E; De Raeve, H; Lepage, D; Van Valckenborgh, E; Van Camp, B; Alvarez, E; Vanderkerken, K

    2008-01-01

    Aplidin® is an antitumour drug, currently undergoing phase II evaluation in different haematological and solid tumours. In this study, we analysed the antimyeloma effects of Aplidin in the syngeneic 5T33MM model, which is representable for the human disease. In vitro, Aplidin inhibited 5T33MMvv DNA synthesis with an IC50 of 3.87 nM. On cell-cycle progression, the drug induced an arrest in transition from G0/G1 to S phase, while Western blot showed a decreased cyclin D1 and CDK4 expression. Furthermore, Aplidin induced apoptosis by lowering the mitochondrial membrane potential, by inducing cytochrome c release and by activating caspase-9 and caspase-3. For the in vivo experiment, 5T33MM-injected C57Bl/KaLwRij mice were intraperitoneally treated with vehicle or Aplidin (90 μg kg−1 daily). Chronic treatment with Aplidin was well tolerated and reduced serum paraprotein concentration by 42% (P<0.001), while BM invasion with myeloma cells was decreased by 35% (P<0.001). Aplidin also reduced the myeloma-associated angiogenesis to basal values. This antiangiogenic effect was confirmed in vitro and explained by inhibition of endothelial cell proliferation and vessel formation. These data indicate that Aplidin is well tolerated in vivo and its antitumour and antiangiogenic effects support the use of the drug in multiple myeloma. PMID:18521088

  14. Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice.

    PubMed

    Pellegatta, S; Poliani, P L; Corno, D; Grisoli, M; Cusimano, M; Ubiali, F; Baggi, F; Bruzzone, M G; Finocchiaro, G

    2006-07-01

    In recent years, the use of dendritic cells (DC), the most powerful antigen presenting cells, has been proposed for the creation of vaccines against gliomas. This approach has been demonstrated to be safe and non-toxic in phase I or I-II trials (2, 3). Immunotherapy plays a central role in the search for new treatments for glioblastoma multiforme (GBM). In particular, several phase I studies have been performed using DC pulsed by GBM proteins as a vaccine for patients with relapsing GBM. The studies demonstrated that DC vaccination is safe and may produce a significant increase in overall survival. As the first step in the preparation of appropriate conditions for a clinical evaluation in Italy, we have performed pre-clinical experiments on immune-competent mice injected intra-cerebrally with syngeneic GL261GBM cells and treated subcutaneously and intra-tumorally with DC loaded with a GL261 homogenate. These results show that vaccination with DC pulsed with a tumor lysate increases considerably survival in mice bearing intracranial glioblastomas and supports the development of DC-based clinical trials for patients with glioblastomas that do not respond to standard therapies.

  15. Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis.

    PubMed

    Morony, S; Capparelli, C; Sarosi, I; Lacey, D L; Dunstan, C R; Kostenuik, P J

    2001-06-01

    Certain malignancies, including breast cancer, frequently metastasize to bone, where the tumor cells induce osteoclasts to locally destroy bone. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, is a negative regulator of osteoclast differentiation, activation, and survival. We tested the ability of recombinant OPG to inhibit tumor-induced osteoclastogenesis, osteolysis, and skeletal tumor burden in two animal models. In a syngeneic model, mouse colon adenocarcinoma (Colon-26) cells were injected into the left ventricle of mice. Treatment with OPG dose-dependently decreased the number and area of radiographically evident lytic bone lesions, which, at the highest dose, were undetectable. Histologically, OPG also decreased skeletal tumor burden and tumor-associated osteoclasts. In a nude mouse model, OPG treatment completely prevented radiographic osteolytic lesions caused by human MDA-MB-231 breast cancer cells. Histologically, OPG decreased skeletal tumor burden by 75% and completely eradicated MDA tumor-associated osteoclasts. In both models, OPG had no effect on metastatic tumor burden in a panel of soft tissue organs. These data indicate that OPG may be an effective therapy for preventing osteolysis and decreasing skeletal tumor burden in patients with bone metastasis.

  16. Induction of murine tumors in adult mice by a combination of either avian sarcoma virus or human adenovirus and syngeneic mouse embryo cells.

    PubMed

    Takeuchi, M; Nitta, K

    1983-01-01

    Primary murine Rous sarcoma was produced in adult mice of seven strains, C57BL/6, DBA/2, BALB/c, C3H/He, CBAJ, AKR, and DDD, by s.c. inoculation of a mixture of 5 X 10(6) chicken tumor cells containing Schmidt-Ruppin Rous sarcoma virus and 9- to 12-day-old mouse embryo cells (MEC) (2 X 10(6) ) of the syngeneic strain. The sarcoma developed at the site of injection in almost all mice tested, but there were some differences in the latent period and the survival time among mouse strains. When the number of cells inoculated was reduced to 5 X 10(4) for chicken tumor cells induced by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-CTC) and 2 X 10(4) for MEC, no tumor was produced in C3H/He mice. These tumors had strain specificity and the Schmidt-Ruppin strain of Rous sarcoma virus genome in masked form. The tumor at the site of injection originated in the embryo cells injected along with SR-CTC. This was confirmed by CBAT6/T6 marker chromosome analysis of the tumor cells of CBA mice induced with SR-CTC plus CBAT6/T6 MEC and also confirmed by transplantation of a C57BL/6 X C3H/He F1 tumor which had been induced with SR-CTC plus C3H/He or C57BL/6 MEC. Tumor induction in adult mouse by a mixture of virus and syngeneic 9- to 14-day-old embryo cells was tested for human adenovirus serotype 12 (Ad12) and simian virus 40. Primary Ad12 tumor was also induced in adult CBA, C3H/He, and DDD mice by 4 X 10(5 to 6) 50% tissue culture infective dose of Ad12 with 5 X 10(6) syngeneic embryo cells. This tumor contained Ad12 T-antigen-positive particles in cells. But in the case of simian virus 40, the tumor did not appear for about 300 days of observation.

  17. Tracking NF-κB activity in tumor cells during ovarian cancer progression in a syngeneic mouse model

    PubMed Central

    2013-01-01

    Background Nuclear factor-kappa B (NF-kappaB) signaling is an important link between inflammation and peritoneal carcinomatosis in human ovarian cancer. Our objective was to track NF-kappaB signaling during ovarian cancer progression in a syngeneic mouse model using tumor cells stably expressing an NF-kappaB reporter. Methods ID8 mouse ovarian cancer cells stably expressing an NF-kappaB-dependent GFP/luciferase (NGL) fusion reporter transgene (ID8-NGL) were generated, and injected intra-peritoneally into C57BL/6 mice. NGL reporter activity in tumors was non-invasively monitored by bioluminescence imaging and measured in luciferase assays in harvested tumors. Ascites fluid or peritoneal lavages were analyzed for inflammatory cell and macrophage content, and for mRNA expression of M1 and M2 macrophage markers by quantitative real-time RT-PCR. 2-tailed Mann-Whitney tests were used for measuring differences between groups in in vivo experiments. Results In ID8-NGL cells, responsiveness of the reporter to NF-kappaB activators and inhibitors was confirmed in vitro and in vivo. ID8-NGL tumors in C57BL/6 mice bore histopathological resemblance to human high-grade serous ovarian cancer and exhibited similar peritoneal disease spread. Tumor NF-kappaB activity, measured by the NGL reporter and by western blot of nuclear p65 expression, was markedly elevated at late stages of ovarian cancer progression. In ascites fluid, macrophages were the predominant inflammatory cell population. There were elevated levels of the M2-like pro-tumor macrophage marker, mannose-receptor, during tumor progression, and reduced levels following NF-kappaB inhibition with thymoquinone. Conclusions Our ID8-NGL reporter syngeneic model is suitable for investigating changes in tumor NF-kappaB activity during ovarian cancer progression, how NF-kappaB activity influences immune cells in the tumor microenvironment, and effects of NF-kappaB-targeted treatments in future studies. PMID:24020521

  18. 9 CFR 113.409 - Tuberculin-PPD Bovis, Intradermic.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... required for the Reference PPD Tuberculin. Allowance should be made for deaths during the sensitization period. (2) Sensitization of guinea pigs. (i) Sensitize one group of guinea pigs to M. bovis. Inject each... the same sensitization and the same PPD tuberculin injection, then divide by the number of animals in...

  19. Lymphoreticular response to a syngeneic rat tumour: gravimetric and histological studies.

    PubMed Central

    Flannery, G. R.; Muller, H. K.; Nairn, R. C.

    1975-01-01

    Gravimetric and histological studies of lymphoreticular tissues during growth of a syngeneic squamous cell carcinoma in Wistar rats show that the regional lymph node anergy reported previously in this system is associated with replacement of paracortical small lymphocytes by large blastoid cells. The regional node continued to gain weight throughout the period of anergy and showed no atrophy and minimal necrosis. Over the same period the spleen increased in both weight and cytotoxicity. Images Fig. 4 Fig. 5 PMID:1174441

  20. Tolerability of intramuscular and intradermal delivery by CELLECTRA(®) adaptive constant current electroporation device in healthy volunteers.

    PubMed

    Diehl, Malissa C; Lee, Jessica C; Daniels, Stephen E; Tebas, Pablo; Khan, Amir S; Giffear, Mary; Sardesai, Niranjan Y; Bagarazzi, Mark L

    2013-10-01

    DNA vaccines are being developed as a potentially safe and effective immunization platform. However, translation of DNA vaccines into a clinical setting has produced results that have fallen short of those generated in a preclinical setting. Various strategies are being developed to address this lack of potency, including improvements in delivery methods. Electroporation (EP) creates transient increases in cell membrane permeability, thus enhancing DNA uptake and leading to a more robust immune response. Here, we report on the safety and tolerability of delivering sterile saline via intramuscular (IM) or intradermal (ID) injection followed by in vivo electroporation using the CELLECTRA(®) adaptive constant current device in healthy adults from two open-label studies. Pain, as assessed by VAS, was highest immediately after EP but diminishes by about 50% within 5 min. Mean VAS scores appear to correlate with the amount of energy delivered and depth of needle insertion, especially for intramuscular EP. Mean scores did not exceed 7 out of 10 or 3 out of 10 for IM and ID EP, respectively. The majority of adverse events included mild to moderate injection site reactions that resolved within one day. No deaths or serious adverse events were reported during the course of either study. Overall, injection followed by EP with the CELLECTRA(®) device was well-tolerated and no significant safety concerns were identified. These studies support the further development of electroporation as a vaccine delivery method to enhance immunogenicity, particularly for diseases in which traditional vaccination approaches are ineffective.

  1. Toll-Like Receptor 9 Activation Rescues Impaired Antibody Response in Needle-free Intradermal DNA Vaccination

    PubMed Central

    Arunachalam, Prabhu S.; Mishra, Ria; Badarinath, Krithika; Selvam, Deepak; Payeli, Sravan K.; Stout, Richard R.; Ranga, Udaykumar

    2016-01-01

    The delivery of plasmid DNA to the skin can target distinct subsets of dermal dendritic cells to confer a superior immune response. The needle-free immunization technology offers a reliable, safe and efficient means to administer intradermal (ID) injections. We report here that the ID injection of DNA vectors using an NF device (NF-ID) elicits a superior cell-mediated immune response, at much lesser DNA dosage, comparable in magnitude to the traditional intramuscular immunization. However, the humoral response is significantly impaired, possibly at the stage of B cell isotype switching. We found that the NF-ID administration deposits the DNA primarily on the epidermis resulting in a rapid loss of the DNA as well as the synthesized antigen due to the faster regeneration rate of the skin layers. Therefore, despite the immune-rich nature of the skin, the NF-ID immunization of DNA vectors may be limited by the impaired humoral response. Additional booster injections are required to augment the antibody response. As an alternative and a viable solution, we rescued the IgG response by coadministration of a Toll-like receptor 9 agonist, among other adjuvants examined. Our work has important implication for the optimization of the emerging needle-free technology for ID immunization. PMID:27658623

  2. Prolonged survival upon ultrasound-enhanced doxorubicin delivery in two syngenic glioblastoma mouse models.

    PubMed

    Kovacs, Zsofia; Werner, Beat; Rassi, Anahita; Sass, Jörn Oliver; Martin-Fiori, Ernst; Bernasconi, Michele

    2014-08-10

    Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans with a very poor prognosis. Chemotherapeutical treatment of GBMs is limited by the blood-brain barrier (BBB). This physical and metabolic barrier separates the blood from the brain parenchyma and prevents the entry of toxins but also of potentially useful chemotherapeutics from the blood into the brain. Microbubble-enhanced focused ultrasound (MB-FUS) has been proposed to disrupt locally and reversibly the BBB to facilitate diffusion of drugs from the micro vasculature into brain tissue. The present study investigates the feasibility and the safety of such an approach in two syngenic mouse models of GBM (GL261 and SMA-560). Local doxorubicin (DOX) concentration in MB-FUS sonicated normal brain tissue as well as in brain tumor tissue was increased as compared to the unsonicated control tissue in the contralateral hemisphere. Moreover, ultrasound mediated BBB disruption, in combination with DOX therapy, resulted in a significant increase of survival and in a slower disease progression in the two syngenic GBM mouse models. In conclusion, our results confirm that MB-ultrasound might ultimately be an effective technology to improve the therapy of GBM, and they provide for the first time evidence that combining MB-FUS with DOX treatment is effective in syngenic mouse models for GBM which can serve as preclinical models to study the impact of immune system on the therapeutic application of MB-FUS chemotherapy.

  3. Pre-exposure prophylaxis against rabies in children: safety of purified chick embryo cell rabies vaccine (Vaxirab N) when administered by intradermal route.

    PubMed

    Ravish, Haradanahalli S; Srikanth, Jayanthi; Ashwath Narayana, Doddabele Hanumanthaiah; Annadani, Rachana; Vijayashankar, Veena; Undi, Malatesh

    2013-09-01

    Animal bites in humans are a public health problem. Children are the most frequently exposed, representing 50% of human exposures in canine rabies infected areas. Pre-exposure vaccination using cell culture vaccines is a safe and effective method of preventing rabies among children in these highly endemic regions. The development of immunological memory after pre exposure vaccination has established long lasting immunity against rabies in humans. The present study assessed the safety of Purified Chick Embryo cell Rabies Vaccine (Vaxirab N) administered as a three-dose intradermal pre-exposure regimen on days 0, 7, and 21 in healthy volunteered children of 5-10 y age group from an urban poor locality in Bangalore, India. One hundred fifty three apparently healthy children of both sexes between 5 and 10 y of age were enrolled in the study and 123 (80.4%) completed all three doses. A total of 405 doses of intradermal vaccine was administered, among which 25 adverse reactions were reported from 17 children. The adverse reactions were pain at the injection site 15 (3.7%), redness 2 (0.5%), itching at the site of injection 1 (0.2%), fatigue 1 (0.2%), fever 3 (0.7%), myalgia 2 (0.5%) and allergy 1 (0.2%). All reactions subsided without any complication. In conclusion, pre exposure vaccination against rabies is a useful tool for protecting children living in highly endemic regions and Vaxirab N has proved to be safe and well tolerated by intradermal route among children.

  4. Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

    PubMed

    Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

    2014-10-15

    Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system.

  5. Intradermal injection of human adipose-derived stem cells accelerates skin wound healing in nude mice.

    PubMed

    Rodriguez, Jonathan; Boucher, Fabien; Lequeux, Charlotte; Josset-Lamaugarny, Audrey; Rouyer, Ondine; Ardisson, Orianne; Rutschi, Héléna; Sigaudo-Roussel, Dominique; Damour, Odile; Mojallal, Ali

    2015-12-08

    The use of stem cells from adipose tissue or adipose-derived stem cells (ASCs) in regenerative medicine could be an interesting alternative to bone marrow stem cells because they are easily accessible and available in large quantities. The aim of this study was to evaluate the potential effect of ASCs on the healing of 12 mm diameter-excisional wounds (around 110 mm(2)) in nude mice. Thirty nude mice underwent surgery to create one 12-mm excisional wound per mouse (spontaneous healing, n = 6; Cytocare® 532, n = 12; ASCs, n = 12). The Galiano wound model was chosen to avoid shrinkage and thus slow the spontaneous healing (SH) of mouse skin, making it closer to the physiology of human skin healing. Transparent dressings were used to enable daily healing time measurements to be taken. Immunohistochemistry, histological and blood perfusion analysis were carried out on the healed skin. The in vivo results showed the effectiveness of using ASCs on reducing the time needed for complete healing to 21.2 days for SH, 17.4 days for vehicle alone (Cytocare® 532) and 14.6 days with the addition of ASCs (p < 0.001). Moreover, cutaneous perfusion of the healed wound was significantly improved in ASC-treated mice compared to SH group, as shown by laser Doppler flowmetry and the quantitation of blood vessels using immunohistochemistry of αsmooth muscle actin. The tolerance and efficacy of cryopreserved ASCs to accelerate the complete closure of the wound by increasing the maturation of the skin and its blood perfusion, shows their therapeutic benefit in the wound healing context.

  6. pH-adjustment and discomfort caused by the intradermal injection of lignocaine.

    PubMed

    Martin, A J

    1990-11-01

    One hundred adult day-case patients who required intravenous access had cannulae inserted using local anaesthesia with 1% lignocaine, 1% lignocaine with adrenaline or the corresponding pH-adjusted solutions. The local anaesthetic solutions were modified by the addition of 1 ml 8.4% sodium bicarbonate to 10 ml lignocaine. Pain scores at different stages of cannulation were noted and showed a significant reduction after use of pH-adjusted solutions (p less than 0.02 for the plain lignocaine, and less than 0.001 for the lignocaine with adrenaline). Modification of the pH of lignocaine solutions by the addition of sodium bicarbonate is a simple method significantly to reduce the discomfort caused by the infiltration of the local anaesthetic.

  7. Effect of an inactivated paratuberculosis vaccine on the intradermal testing of goats for tuberculosis.

    PubMed

    Chartier, Christophe; Mercier, Pascale; Pellet, Marie-Pierre; Vialard, Jaquemine

    2012-03-01

    The effect of an inactivated paratuberculosis vaccine on the diagnosis of tuberculosis (TB) in goats was investigated in a herd with a history of clinical paratuberculosis but which was free of TB. Cohorts of animals in 2006, 2008 and 2009, were vaccinated once at 1 month of age, and 50% of the 2006 cohort served as unvaccinated controls. The goats were aged 8 months, 20 months and 3.5 years old at the time of the survey. All animals were assessed using a single intradermal injection of bovine tuberculin purified protein derivative (PPD) (SID test), or using both bovine and avian PPD (CID test). An interferon (IFN)-γ assay using both bovine and avian PPD was carried out on the 2006 cohort and was interpreted according to three different 'cut-off' points. No unvaccinated (control) animals tested positive to any of the assays, confirming that the herd was TB-free. The SID test had a low specificity in vaccinated animals at 8 and 20 months of age, whereas the CID test demonstrated 100% specificity in animals ≥20 months-old. The specificity of IFN-γ assay was less than maximal for vaccinated animals 3.5 years old as small numbers of false positives were detected, although this depended on the chosen cut-off point. The study findings demonstrate that the use of an inactivated paratuberculosis vaccine in goats <1 month-old in a TB-free herd does not result in false positives to a CID test for TB when performed in animals ≥20 months-old. Copyright © 2011. Published by Elsevier Ltd.

  8. Onset and duration of intradermal mixtures of bupivacaine and lidocaine with epinephrine

    PubMed Central

    Collins, James B; Song, Juhee; Mahabir, Raman C

    2013-01-01

    BACKGROUND/OBJECTIVE: Bupivacaine and lidocaine are often used concurrently, in theory, to combine the more rapid onset of lidocaine and the longer duration of bupivacaine. The purpose of this study was to evaluate this concept. METHODS: Twenty-five subjects were enrolled in a double-blinded, randomized block design study to evaluate the onset and duration of four different mixtures of lidocaine and bupivacaine with epinephrine. The study was designed to achieve 80% power to detect an effect size of 0.37 at 5% overall significance. The four mixtures tested were: 0.25% bupivacaine with epinephrine (1:200,000); 1% lidocaine with epinephrine (1:100,000); 0.125% bupivacaine and 0.5% lidocaine with epinephrine (1:150,000); and 0.25% bupivacaine and 1% lidocaine with epinephrine (1:150,000). Four intradermal injections were made in the volar forearms of each participant. Time to effect and duration were measured by sensation of a sharp skin prick. RESULTS: Mean time to onset ranged from 12 s to 29 s without statistical significance across all tested solutions (P=0.891). Mean duration of effect ranged from 6 h 38 min to 7 h 25 min with a statistically significant difference across the tested solutions (P=0.036). CONCLUSIONS: No statistical benefit was measured when comparing lidocaine with epinephrine, bupivacaine with epinephrine, and mixtures of these local anesthetics with regard to onset of action. While a statistical difference was observed in duration of effect, the clinical benefit measured was narrow. PMID:24431939

  9. Neurotransmitter Supression of the In Vitro Generation of a Cytotoxic T- Lymphocyte Response against the Syngeneic MOPC-315 Plasmacytoma

    DTIC Science & Technology

    1991-01-01

    Cytotoxic activity was generated by coculture of normal spleen lymphocytes from BALB/c mice with syngeneic MOPC-315 plasmacytoma cells and was assayed by...studies were purchased from Sigma, St. Louis, MO. Tumor Cells. MOPC-315 plasmacytomas were maintained in vivo as subcutaneous tumors as previously...syngeneic MOPC-315 plasmacytoma . These molecules were inhibitory at a concentration of 100 pM, a nontoxic concentration not unexpected for localized

  10. Usefulness of intradermal test and patch test in the diagnosis of nonimmediate reactions to metamizol.

    PubMed

    Macías, E; Ruiz, A; Moreno, E; Laffond, E; Dávila, I; Lorente, F

    2007-12-01

    Metamizole is a pyrazolone derivative, and its most common reactions are IgE-mediated reaction and idiosyncratic reactions. Non-immediate reactions are poorly described and there are very few reports on non-immediate reactions to pyrazolones. We evaluated 12 patients (nine men) who consulted for a non-immediate reaction after metamizol administration. We performed cutaneous tests (skin prick tests and immediate and delayed intradermal tests) and epicutaneous tests, and, if necessary, an oral challenge test. All skin prick and intradermal tests, if necessary, were negative in immediate reading. Delayed intradermal tests were positive in six of 10 patients (60%) and epicutaneous tests were positive in four of 11 patients (36%). Three cases (25%), were diagnosed by a positive oral challenge test. Delayed-reading intradermal tests and patch tests are useful tools in the diagnosis of nonimmediate reactions to pyrazolones and should be considered the first step when evaluating these type of reactions. Intradermal test appears to be more sensitive than patch test. The positivity of skin tests suggests an immunological reaction, probably mediated by T lymphocytes, but further studies are required.

  11. Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011-2012 influenza season: a comparative effectiveness study using the Valencia health care information system.

    PubMed

    Puig-Barberà, J; Natividad-Sancho, A; Calabuig-Pérez, J; Lluch-Rodrigo, J A; Pastor-Villalba, E; Martínez-Úbeda, S; Díez-Domingo, J

    2014-09-22

    The use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking. We conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011-2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR). Overall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal-TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50-0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52-0.85). During the 2011-2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Transgene expression and local tissue distribution of naked and polymer-condensed plasmid DNA after intradermal administration in mice

    PubMed Central

    Palumbo, R. Noelle; Zhong, Xiao; Panus, David; Han, Wenqing; Ji, Weihang; Wang, Chun

    2012-01-01

    DNA vaccination using cationic polymers as carriers has the potential to be a very powerful method of immunotherapy, but typical immune responses generated have been less than robust. To better understand the details of DNA vaccine delivery in vivo, we prepared polymer/DNA complexes using three structurally distinct cationic polymers and fluorescently labeled plasmid DNA and injected them intradermally into mice. We analyzed transgene expression (luciferase) and the local tissue distribution of the labeled plasmid at the injection site at various time points (from hours to days). Comparable numbers of luciferase expressing cells were observed in the skin of mice receiving naked plasmid or polyplexes one day after transfection. At day 4, however, the polyplexes appeared to result in more transfected skin cells than naked plasmid. Live animal imaging revealed that naked plasmid dispersed quickly in the skin of mice after injection and had a wider distribution than any of the three types of polyplexes. However, naked plasmid level dropped to below detection limit after 24 h, whereas polyplexes persisted for up to 2 weeks. The PEGylated polyplexes had a significantly wider distribution in the tissue than the nonPEGylated polyplexes. PEGylated polyplexes also distributed more broadly among dermal fibroblasts and allowed greater interaction with antigen-presenting cells (APCs) (dendritic cells and macrophages) starting at around 24 h post-injection. By day 4, co-localization of polyplexes with APCs was observed at the injection site regardless of polymer structure, whereas small amounts of polyplexes were found in the draining lymph nodes. These in vivo findings demonstrate the superior stability of PEGylated polyplexes in physiological milieu and provide important insight on how cationic polymers could be optimized for DNA vaccine delivery. PMID:22300619

  13. Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes.

    PubMed

    Abadie, Valérie; Badell, Edgar; Douillard, Patrice; Ensergueix, Danielle; Leenen, Pieter J M; Tanguy, Myriam; Fiette, Laurence; Saeland, Sem; Gicquel, Brigitte; Winter, Nathalie

    2005-09-01

    The early innate response after Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination is poorly characterized but probably decisive for subsequent protective immunity against tuberculosis. Therefore, we vaccinated mice with fluorescent BCG strains in the ear dorsum, as a surrogate of intradermal vaccination in humans. During the first 3 days, we tracked BCG host cells migrating out of the dermis to the auricular draining lymph nodes (ADLNs). Resident skin dendritic cells (DCs) or macrophages did not play a predominant role in early BCG capture and transport to ADLNs. The main BCG host cells rapidly recruited both in the dermis and ADLNs were neutrophils. Fluorescent green or red BCG strains injected into nonoverlapping sites were essentially sheltered by distinct neutrophils in the ADLN capsule, indicating that neutrophils had captured bacilli in peripheral tissue and transported them to the lymphoid organ. Strikingly, we observed BCG-infected neutrophils in the lumen of lymphatic vessels by confocal microscopy on ear dermis. Fluorescence-labeled neutrophils injected into the ears accumulated exclusively into the ipsilateral ADLN capsule after BCG vaccination. Thus, we provide in vivo evidence that neutrophils, like DCs or inflammatory monocytes, migrate via afferent lymphatics to lymphoid tissue and can shuttle live microorganisms.

  14. The effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica.

    PubMed

    Sumracki, Nicole M; Hutchinson, Mark R; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond B; Rolan, Paul

    2012-01-01

    Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin. It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate

  15. Syngeneic murine ovarian cancer model reveals that ascites enriches for ovarian cancer stem-like cells expressing membrane GRP78

    PubMed Central

    Mo, Lihong; Bachelder, Robin E.; Kennedy, Margaret; Chen, Po-Han; Chi, Jen-Tsan; Berchuck, Andrew; Cianciolo, George; Pizzo, Salvatore V.

    2016-01-01

    Ovarian cancer patients are generally diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage III/IV, when ascites is common. The volume of ascites correlates positively with the extent of metastasis and negatively with prognosis. Membrane GRP78, a stress-inducible endoplasmic reticulum chaperone that is also expressed on the plasma membrane (memGRP78) of aggressive cancer cells, plays a crucial role in the embryonic stem cell maintenance. We studied ascites effects on ovarian cancer stem-like cells using a syngeneic mouse model. Our study demonstrates that ascites-derived tumor cells from mice injected intraperitoneally with murine ovarian cancer cells (ID8) express increased memGRP78 levels compared to ID8 cells from normal culture. We hypothesized that these ascites associated memGRP78+ cells are cancer stem-like cells (CSC). Supporting this hypothesis, we show that memGRP78+ cells isolated from murine ascites exhibit increased sphere forming and tumor initiating abilities compared to memGRP78− cells. When the tumor microenvironment is recapitulated by adding ascites fluid to cell culture, ID8 cells express more memGRP78 and increased self-renewing ability compared to those cultured in medium alone. Moreover, compared to their counterparts cultured in normal medium, ID8 cells cultured in ascites, or isolated from ascites, show increased stem cell marker expression. Antibodies directed against the carboxy-terminal domain of GRP78: 1) reduce self-renewing ability of murine and human ovarian cancer cells pre-incubated with ascites and 2) suppress a GSK3α-AKT/SNAI1 signaling axis in these cells. Based on these data, we suggest that memGRP78 is a logical therapeutic target for late stage ovarian cancer. PMID:25589495

  16. Improved Insulin Pharmacokinetics Using a Novel Microneedle Device for Intradermal Delivery in Patients with Type 2 Diabetes

    PubMed Central

    Levin, Yotam; Raz, Itamar; Cahn, Avivit

    2016-01-01

    Abstract Background: Currently available short-acting insulin analogs have slower absorption compared with endogenous insulin occasionally resulting in immediate postprandial hyperglycemia. Intradermal (ID) injection facilitates faster drug absorption and may result in improved insulin pharmacokinetics. Methods: Seventeen patients with type 2 diabetes were included in this single-center, pilot, open-label crossover study. Patients received 0.2 U/kg Insulin aspart ID injections using a MicronJet (MJ) needle and subcutaneous (SC) injections, using a conventional needle in a crossover design. Thirteen patients were studied under fasting conditions and four before a standard meal test. The pharmacokinetic/pharmacodynamic (PK/PD) profile, as well as the safety and tolerability of injections, was compared. Results: Fourteen patients completed the study per-protocol. ID versus SC injection demonstrated significantly shorter Tmax (median 35 vs. 87.5 min [P < 0.001]), while the Cmax did not significantly differ (median 80 vs. 55 μU/mL [P = 0.085]). Median insulin area under the curve (AUC; 360 min) did not differ between the groups (9914 vs. 10,936 μU/mL/min [p = 0.077]), yet 0–60 min insulin AUC was higher with ID versus SC injection (mean ± SD 3821 ± 1429 vs. 2534 ± 737 μU/mL/min [p = 0.01]) and 4–6 h AUC was lower with ID versus SC injection (mean ± SD 2054 ± 858 vs. 2929 ± 1412 μU/mL/min [p = 0.02]). The relative bioavailability of the ID versus the SC insulin (AUCID/AUCSC) was similar (median 0.91 [95% confidence interval 0.73–1.27]). Conclusions: ID insulin injection delivered through an MJ needle demonstrated superior PK profile compared with conventional SC administration, including shorter Tmax and higher early and lower late exposure in patients with type 2 diabetes. This may help achieve better insulin coverage of meals and lower postprandial glucose excursions. PMID:27500713

  17. Vesicular stomatitis virus expressing interferon-β is oncolytic and promotes antitumor immune responses in a syngeneic murine model of non-small cell lung cancer.

    PubMed

    Patel, Manish R; Jacobson, Blake A; Ji, Yan; Drees, Jeremy; Tang, Shaogeng; Xiong, Kerry; Wang, Hengbing; Prigge, Jennifer E; Dash, Alexander S; Kratzke, Andrea K; Mesev, Emily; Etchison, Ryan; Federspiel, Mark J; Russell, Stephen J; Kratzke, Robert A

    2015-10-20

    Vesicular stomatitis virus (VSV) is a potent oncolytic virus for many tumors. VSV that produces interferon-β (VSV-IFNβ) is now in early clinical testing for solid tumors. Here, the preclinical activity of VSV and VSV-IFNβ against non-small cell lung cancer (NSCLC) is reported. NSCLC cell lines were treated in vitro with VSV expressing green fluorescence protein (VSV-GFP) and VSV-IFNβ. VSV-GFP and VSV-IFNβ were active against NSCLC cells. JAK/STAT inhibition with ruxolitinib re-sensitized resistant H838 cells to VSV-IFNβ mediated oncolysis. Intratumoral injections of VSV-GFP and VSV-IFNβ reduced tumor growth and weight in H2009 nude mouse xenografts (p < 0.01). A similar trend was observed in A549 xenografts. Syngeneic LM2 lung tumors grown in flanks of A/J mice were injected with VSV-IFNβ intratumorally. Treatment of LM2 tumors with VSV-IFNβ resulted in tumor regression, prolonged survival (p < 0.0001), and cure of 30% of mice. Intratumoral injection of VSV-IFNβ resulted in decreased tumor-infiltrating regulatory T cells (Treg) and increased CD8+ T cells. Tumor cell expression of PDL-1 was increased after VSV-IFNβ treatment. VSV-IFNβ has potent antitumor effects and promotes systemic antitumor immunity. These data support further clinical investigation of VSV-IFNβ for NSCLC.

  18. Safety of the intradermal Copenhagen 1331 BCG vaccine in neonates in Durban, South Africa.

    PubMed Central

    Jeena, P. M.; Chhagan, M. K.; Topley, J.; Coovadia, H. M.

    2001-01-01

    OBJECTIVE: To evaluate the safety of the intradermal Copenhagen BCG vaccine in neonates at different levels of delivery and neonatal units of the Durban Functional Region and surrounding regions. METHODS: A prospective study was carried out over a two-year period between July 1997 and June 1999. All neonates who had been vaccinated with the intradermal vaccine were evaluated at immunization clinics six weeks after immunization, or earlier if adverse effects occurred. FINDINGS: In total, 9763 neonates were examined: in 95.4% the vaccination scar had healed and 1.5% had no visible scar. Adverse events occurred in 3.1%. The proportion of neonates with no visible vaccination scars decreased over the study period, as did the number with adverse events. The lowest rate of adverse events and the highest rates of healed vaccination scars were seen in the tertiary hospital and regional and district hospitals that were in close proximity to the academic centre involved in this study. CONCLUSIONS: In the study sites, the transition from the percutaneous to intradermal route of administration of BCG vaccine was successful and took place without incurring unacceptably high rates of adverse events. To minimize adverse events, however, it is essential to continue training health personnel involved in implementing intradermal BCG vaccination programmes. PMID:11357213

  19. Ag coated microneedle based surface enhanced Raman scattering probe for intradermal measurements

    NASA Astrophysics Data System (ADS)

    Yuen, Clement; Liu, Quan

    2013-06-01

    We propose a silver coated microneedle to detect test molecules, including R6G and glucose, positioned at a depth of more than 700 μm below a skin phantom surface for mimicking intradermal surface-enhanced Raman scattering measurements.

  20. Comparison of absorbable and nonabsorbable sutures for intradermal skin closure in cats

    PubMed Central

    Papazoglou, Lysimachos G.; Tsioli, Vassiliki; Papaioannou, Nikolaos; Georgiadis, Marios; Savvas, Ioannis; Prassinos, Nikitas; Kouti, Vasileia; Bikiaris, Dimitrios; Hadzigiannakis, Christos; Zavros, Nikolaos

    2010-01-01

    Paired skin incisions were made in 6 cats and closed intradermally with the copolymer of glycolide, ɛ-caprolacton, and trimethylene-carbonate, or polypropylene suture. The macroscopic and histologic appearance of the incisions was compared. Polypropylene suture compared favorably to glycolide, ɛ-caprolacton, and trimethylene-carbonate suture for closure of skin incisions in cats. PMID:20885834

  1. Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal immunization

    PubMed Central

    Andrianov, Alexander K.; DeCollibus, Daniel P.; Gillis, Helice A.; Kha, Henry H.; Marin, Alexander; Prausnitz, Mark R.; Babiuk, Lorne A.; Townsend, Hugh; Mutwiri, George

    2009-01-01

    Intradermal immunization using microfabricated needles represents a potentially powerful technology, which can enhance immune responses and provide antigen sparing. Solid vaccine formulations, which can be coated onto microneedle patches suitable for simple administration, can also potentially offer improved shelf-life. However the approach is not fully compatible with many vaccine adjuvants including alum, the most common adjuvant used in the vaccine market globally. Here, we introduce a polyphosphazene immuno adjuvant as a biologically potent and synergistic constituent of microneedle-based intradermal immunization technology. Poly[di(carboxylatophenoxy)phosphazene], PCPP, functions both as a vaccine adjuvant and as a key microfabrication material. When used as part of an intradermal delivery system for hepatitis B surface antigen, PCPP demonstrates superior activity in pigs compared to intramascular administration and significant antigen sparing potential. It also accelerates the microneedle fabrication process and reduces its dependence on the use of surfactants. In this way, PCPP-coated microneedles may enable effective intradermal vaccination from an adjuvanted patch delivery system. PMID:19864632

  2. Skin closure in vascular neurosurgery: A prospective study on absorbable intradermal suture versus nonabsorbable suture.

    PubMed

    Pereira, Julio Leonardo Barbosa; Vieira, Gerival; de Albuquerque, Lucas Alverne Freitas; Mendes, George de Albuquerque Cavalcanti; Salles, Ludmila Rezende; de Souza, André Felipe Ferreira; Dellaretti, Marcos; de Sousa, Atos Alves

    2012-01-01

    The craniotomy performed with minimal hair removal and closure with intradermal suture alone is an option in neurosurgical procedures, which can help faster psychological recovery of the patient, as it allows a better cosmetic result. This study is aimed at evaluating if such method is safe and effective, compared with continuous skin sutures with 2-0 nylon. We analyzed the sutures in 117 patients undergoing craniotomies for cerebral aneurysm clipping. In the case group (n = 49), closure of the scalp was performed only with intradermal absorbable sutures using wire Monocryl(®) 2-0. In the control group (n = 68), closure was performed with continuous suture using 2-0 nylon. The case group was composed of 49 patients in whom just intradermal suture was performed. One (2.2%) patient developed wound infection and was given proper medical treatment. No cases of dehiscence or cerebrospinal fluid leaks were observed. The control group was composed of 68 patients in whom the skin was closed with 2-0 nylon continuous suture. Three (5.3%) patients developed wound infection and were given proper medical treatment. There were no cases of wound dehiscence. The overall infection rate in the control group was 4%. There was no statistically significant difference in the number of wound infections between the two groups (P = 0.73). The closure with intradermal suture alone in craniotomies is as safe as the traditional skin closure with nylon sutures, besides eliminating the need for suture removal and providing a cosmetic advantage.

  3. Phase I Randomized Clinical Trial of VRC DNA and rAd5 HIV-1 Vaccine Delivery by Intramuscular (IM), Subcutaneous (SC) and Intradermal (ID) Administration (VRC 011)

    PubMed Central

    Enama, Mary E.; Ledgerwood, Julie E.; Novik, Laura; Nason, Martha C.; Gordon, Ingelise J.; Holman, LaSonji; Bailer, Robert T.; Roederer, Mario; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.

    2014-01-01

    Background Phase 1 evaluation of the VRC HIV DNA and rAd5 vaccines delivered intramuscularly (IM) supported proceeding to a Phase 2 b efficacy study. Here we report comparison of the IM, subcutaneous (SC) and intradermal (ID) routes of administration. Methods Sixty subjects were randomized to 6 schedules to evaluate the IM, SC or ID route for prime injections. Three schedules included DNA primes (Wks 0,4,8) and 3 schedules included rAd5 prime (Wk0); all included rAd5 IM boost (Wk24). DNA vaccine dosage was 4 mg IM or SC, but 0.4 mg ID, while all rAd5 vaccinations were 1010 PU. All injections were administered by needle and syringe. Results Overall, 27/30 subjects completed 3 DNA primes; 30/30 subjects completed rAd5 primes. Mild local pruritus (itchiness), superficial skin lesions and injection site nodules were associated with ID and SC, but not IM injections. All routes induced T-cell and antibody immune responses after rAd5 boosting. Overall, >95% had Env antibody and >80% had Env T-cell responses. Conclusions The pattern of local reactogenicity following ID and SC injections differed from IM injections but all routes were well-tolerated. There was no evidence of an immunogenicity advantage following SC or ID delivery, supporting IM delivery as the preferred route of administration. Trial Registration Clinicaltrials.gov NCT00321061 PMID:24621858

  4. Concurrent MEK targeted therapy prevents MAPK pathway reactivation during BRAFV600E targeted inhibition in a novel syngeneic murine glioma model

    PubMed Central

    Murphy, Nicole E.; Meyers, Ian D.; Daynac, Mathieu; Truffaux, Nathalene; Truong, Albert Y.; Nicolaides, Theodore P.; McMahon, Martin; Berger, Mitchel S.; Phillips, Joanna J.; James, David C.; Petritsch, Claudia K.

    2016-01-01

    Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback activation of mitogen-activated protein kinase (MAPK) signaling in melanoma, we developed a luciferase-modified cell line (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma, and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted inhibition. Immunocompetent, syngeneic FVB/N mice with intracranial grafts of 2341luc were tested for effects of BRAFV600E and MEK inhibitor treatments, with bioluminescence imaging up to 14-days after start of treatment and survival analysis as primary indicators of inhibitor activity. Intracranial injected tumor cells consistently generated high-grade glioma-like tumors in syngeneic mice. Intraperitoneal daily delivery of BRAFV600E inhibitor dabrafenib only transiently suppressed MAPK signaling, and rather increased Akt signaling and failed to extend survival for mice with intracranial 2341luc tumor. MEK inhibitor trametinib delivered by oral gavage daily suppressed MAPK pathway more effectively and had a more durable anti-growth effect than dabrafenib as well as a significant survival benefit. Compared with either agent alone, combined BRAFV600E and MEK inhibitor treatment was more effective in reducing tumor growth and extending animal subject survival, as corresponding to sustained MAPK pathway inhibition. Results derived from the 2341luc engraftment model application have clinical implications for the management of BRAFV600E glioma. PMID:27713119

  5. CXCL10 alters the tumour immune microenvironment and disease progression in a syngeneic murine model of high-grade serous ovarian cancer.

    PubMed

    K Au, Katrina; Peterson, Nichole; Truesdell, Peter; Reid-Schachter, Gillian; Khalaj, Kasra; Ren, Runhan; Francis, Julie-Ann; Graham, Charles H; Craig, Andrew W; Koti, Madhuri

    2017-06-01

    We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC. ID8 ovarian cancer cells were engineered for stable knockdown (KD) and overexpression (OX) of CXCL10. The OX and KD cell line derivatives, along with their respective vector controls, were implanted in immunocompetent C57BL/6 mice via intra-peritoneal injections. At end point, immune transcriptomic profiling of tumour tissues and multiplex cytokine profiling of ascites, was performed. Effect of CXCL10 expression on the tumour vasculature and tumour cell proliferation was evaluated by CD31 and Ki67 immunostaining, respectively. Increased CXCL10 expression led to decreased tumour burden and malignant ascites accumulation in the ID8 syngeneic murine model of HGSC. The ascites levels of IL-6 and VEGF were significantly reduced in OX mice compared to the vector controls. The OX tumours also showed reduced vasculature (CD31) and proliferative index (Ki67) compared to the control tumours. Significantly higher expression of genes associated with antigen processing, apoptosis and T cell function was observed in OX tumours compared to the controls. Reduced CXCL10 expression in tumours from KD mice led to increased ascites accumulation and disease progression compared to the controls. CXCL10 is a positive determinant of anti-tumour immune responses in HGSC TME and disease progression. These findings are foundational for future translational studies aimed at improving treatment response and survival in HGSC

  6. Ly phenotype of T cells cytotoxic for syngeneic mouse mammary tumors: evidence for T cell interactions.

    PubMed Central

    Stutman, O; Shen, F W; Boyse, E A

    1977-01-01

    Specific cell-mediated cytotoxicity (CMC) of lymph node cells from immunized C3Hf mice, against syngeneic C3H/Umc mammary tumor cells, assayed in vitro, is effected by T lymphocytes. This CMC response is biphasic, with an early peak attained within 6 hr and a second major peak beginning at about 18 hr. Effector cells of both the early minor and late major phases of the response belong to the Ly23 set. Other T cell sets evidently play no part in the early effector response. But specifically activated Ly1 cells help or amplify the major late-phase response. Nevertheless, the mixture of specifically activated Ly1 and Ly23 sets still does not completely reconstitute the late response, which implies that the Ly123 set is also needed for maximal expression of CMC in this system. These Ly123 cells must come from specifically immunized donors. It appears, therefore, that maximal CMC is achieved by the participation of specific Ly123 cells which in the late phase directly or indirectly give rise to Ly23 killer cells. Thus, although killing of syngeneic mammary tumor cells in the CMC assay is invariably effected by cells of the Ly23 set, specifically activated cells of the Ly1 set, and probably of the Ly123 set also, are participants in the interactions needed to produce a maximal CMC response. PMID:304579

  7. Neuropathological Sequelae of Long-Term Allogeneic and Syngeneic Neural Transplantation into the Hippocampus

    PubMed Central

    Patel, Sanjay N.; Kershaw, Tim R.; Williams, John; Gray, Jeffrey A.; Lantos, Peter L.; Sinden, John D.

    1994-01-01

    The long-term fate of multiple intrahippocampal allogeneic transplants of fetal basal forebrain tissue was studied in neonatally tolerised and immunised groups of rats with lesions of the fimbria-fornix. Despite the good survival of the allografts in all groups, unexpected transplant-associated host hippo-campal neuropathology was discovered 12 months after transplantation, which consisted of (i) CA1 cell degeneration and (ii) abnormal accumulations of phosphorylated neurofilaments in neuronal perikarya and axonal swellings only within the host hippocampal neuropil and not of the transplanted tissue. This neurofilament abnormality, identified by RT97 immunohistochemistry, was significantly greater in the transplanted rats compared to the non-grafted lesion-only and sham-lesioned rats (p<0.01). The same type of neurofilament abnormality was again observed in a second, separate experiment using unilateral and bilateral syngeneic and allogeneic transplants. The neuropathology was significantly (p<0.05) greater in the transplanted side of the unilateral transplanted rats compared to the non-transplanted lesion-only control side of the same animals, showing that transplantation per se was a major factor involved in the pathogenesis of this neuropathology, irrespective of the type of transplant (syngeneic or allogeneic). In addition, a small degree of neurofilament abnormality was also found within the transplants in the second experiment, but not in the first. The results show that, under certain conditions, specific local neuropathological damage to the surrounding host neural tissue can develop in long-surviving allografted and syngrafted animals. PMID:7578437

  8. Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow

    SciTech Connect

    Hartnett, L.C.

    1983-01-01

    Generally, organ grafts from one individual animal to another are rejected in one-two weeks. However, if the recipients are given Total Body Irradiation (TBI) just prior to grafting, followed by reconstitution of hemopoietic function with syngeneic (recipient-type) bone marrow cells, then vascularized organ grafts are permanently accepted. Initially after irradiation, it is possible to induce tolerance to many strain combinations in rats. This thesis examines the system of TBI as applied to the induction of tolerance in LEW recipients of WF cardiac allografts. These two rat strains are mismatched across the entire major histocompatibility complex. When the LEW recipient are given 860 rads, a WF cardiac allograft and LEW bone marrow on the same day, 60% of the grafts are accepted. Methods employed to improve the rate of graft acceptance include: treating either donor or recipient with small amounts of methotrexate, or waiting until two days after irradiation to repopulate with bone marrow. It seems from these investigations of some of the early events in the induction of tolerance to allografts following TBI and syngeneic marrow reconstitution that an immature cell population in the bone marrow interacts with a radioresistant cell population in the spleen to produce tolerance to completely MHC-mismatched allografts.

  9. The Evolutionary Relationships between Endosymbiotic Green Algae of Paramecium bursaria Syngens Originating from Different Geographical Locations.

    PubMed

    Zagata, Patrycja; Greczek-Stachura, Magdalena; Tarcz, Sebastian; Rautian, Maria

    2016-01-01

    Paramecium bursaria (Ehrenberg 1831), a freshwater ciliate, typically harbors hundreds of green algal symbionts inside the cell. The aim of present study was the molecular identification of newly analyzed P. bursaria symbionts. The second aspect of the present survey was testing a hypothesis whether endosymbionts prefer the specified syngen of the host, and the specified geographical distribution. Ten strains of endosymbionts isolated from strains of P. bursaria originating from different geographical locations were studied. We analyzed for the first time, both the fragment of plastid genome containing 3'rpl36-5' infA genes and a fragment of a nuclear gene encoding large subunit ribosomal RNA (LSU rDNA). The analysis of the LSU rDNA sequences showed the existence of 3 haplotypes and the haplotype diversity of 0.733, and 8 haplotypes for the 3'rpl36-5' infA gene fragment and haplotype diversity of 0.956. The endosymbionts isolated from P. bursaria strains were identified as Chlorella vulgaris, Ch. variabilis and Micractinium conductrix. There was no correlation between the syngen of P. bursaria and the species of endosymbiont.

  10. Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine.

    PubMed

    Seo, Yu Bin; Lee, Jacob; Song, Joon Young; Choi, Hee Jung; Cheong, Hee Jin; Kim, Woo Joo

    2016-01-01

    Several studies have reported poor immune responses to conventional influenza vaccines in HIV-infected individuals. This study sought to elicit more potent immunogenicity in HIV-infected adults using an intradermal vaccine compared with a conventional intramuscular vaccine. This multicenter, randomized, controlled, open-label study was conducted at 3 university hospitals during the 2011/2012 pre-influenza season. Three vaccines were used in HIV-infected adults aged 18 - 60 years: an inactivated intramuscular vaccine (Agrippal), a reduced-content intradermal vaccine (IDflu9μg) and a standard-content intradermal vaccine (IDflu15μg). Serum hemagglutination-inhibiting (HI) antibodies and INF-γ ELISpot assay were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded for 7 d. A total of 28 Agrippal, 30 IDflu9μg, and 28 IDflu15μg volunteers were included in this analysis. One month after vaccination, the GMTs and differences in INF-γ ELISpot assay results were similar among the 3 groups. Seroprotection rates, seroconversion rates and mean fold increases (MFI) among the 3 groups were also similar, at approximately 80%, 50-60% and 2.5 - 10.0, respectively. All three vaccines satisfied the CHMP criteria for the A/H1N1 and A/H3N2 strains, but not those for the B strain. In univariate analysis, no demographic or clinical factors, including age, CD4+ T-cell counts, HIV viral load, ART status and vaccine type, were related to failure to achieve seroprotection. The three vaccines were all well-tolerated and all reported reactions were mild to moderate. However, there was a tendency toward a higher incidence of local and systemic reactions in the intradermal vaccine groups. The intradermal vaccine did not result in higher immunogenicity compared to the conventional intramuscular vaccine, even with increased antigen dose.

  11. Intradermal cytosine-phosphate-guanosine treatment reduces lung inflammation but induces IFN-γ-mediated airway hyperreactivity in a murine model of natural rubber latex allergy.

    PubMed

    Haapakoski, Rita; Karisola, Piia; Fyhrquist, Nanna; Savinko, Terhi; Wolff, Henrik; Turjanmaa, Kristiina; Palosuo, Timo; Reunala, Timo; Lauerma, Antti; Alenius, Harri

    2011-05-01

    Asthma and other allergic diseases are continuously increasing, causing considerable economic and sociologic burden to society. The hygiene hypothesis proposes that lack of microbial T helper (Th) 1-like stimulation during early childhood leads to increased Th2-driven allergic disorders later in life. Immunostimulatory cytosine-phosphate-guanosine (CpG)-oligodeoxynucleotide motifs are candidate molecules for immunotherapeutic studies, as they have been shown to shift the Th2 response toward the Th1 direction and reduce allergic symptoms. Using natural rubber latex (NRL)-induced murine model of asthma, we demonstrated that intradermal CpG administration with allergen reduced pulmonary eosinophilia, mucus production, and Th2-type cytokines, but unexpectedly induced airway hyperreactivity (AHR) to inhaled methacholine, one of the hallmarks of asthma. We found that induction in AHR was dependent on STAT4, but independent of STAT6 signaling. CpG treatment increased production of IFN-γ in the airways and shifted the ratio of CD4(+):CD8(+) T cells toward CD8(+) dominance. By blocking soluble IFN-γ with neutralizing antibody, AHR diminished and the CD4(+):CD8(+) ratio returned to CD4(+) dominance. These results indicate that increased production of IFN-γ in the lungs may lead to severe side effects, such as enhancement of bronchial hyperreactivity to inhaled allergen. This finding should be taken into consideration when planning prophylaxis treatment of asthma with intradermal CpG injections.

  12. Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac children.

    PubMed

    Leonardi, Salvatore; Praticò, Andrea Domenico; Lionetti, Elena; Spina, Massimo; Vitaliti, Giovanna; La Rosa, Mario

    2012-10-28

    To compare intradermal (ID) and intramuscular (IM) booster doses, which have been used in healthy and high risk subjects, such as healthcare workers, haemodialysis patients, human immunodeficiency virus patients, and renal transplant recipients unresponsive to initial hepatitis B vaccination, in celiac individuals. We conducted our study on 58 celiac patients, vaccinated in the first year of life, whose blood analysis had showed the absence of protective hepatitis B virus (HBV) antibodies. All patients had received the last vaccine injection at least one year before study enrolment and they had been on a gluten free diet for at least 1 year. In all patients we randomly performed an HBV vaccine booster dose by ID or IM route. Thirty celiac patients were revaccinated with recombinant hepatitis B vaccine (Engerix B) 2 μg by the ID route, while 28 celiac patients were revaccinated with Engerix B 10 μg by the IM route. Four weeks after every booster dose, the anti-hepatitis B surface (HBs) antibody titer was measured by an enzyme-linked immune-adsorbent assay. We performed a maximum of three booster doses in patients with no anti-HBs antibodies after the first or the second vaccine dose. The cut off value for a negative anti-HBs antibody titer was 10 IU/L. Patients with values between 10 and 100 IU/L were considered "low responders" while patients with an antibody titer higher than 1000 IU/L were considered "high responders". No significant difference in age, gender, duration of illness, and years of gluten intake was found between the two groups. We found a high percentage of "responders" after the first booster dose (ID = 76.7%, IM = 78.6%) and a greater increase after the third dose (ID = 90%, IM = 96.4%) of vaccine in both groups. Moreover we found a significantly higher number of high responders (with an anti-HBs antibody titer > 1000 IU/L) in the ID (40%) than in the IM (7.1%) group, and this difference was evident after the first booster dose of vaccination (P

  13. Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac children

    PubMed Central

    Leonardi, Salvatore; Praticò, Andrea Domenico; Lionetti, Elena; Spina, Massimo; Vitaliti, Giovanna; Rosa, Mario La

    2012-01-01

    AIM: To compare intradermal (ID) and intramuscular (IM) booster doses, which have been used in healthy and high risk subjects, such as healthcare workers, haemodialysis patients, human immunodeficiency virus patients, and renal transplant recipients unresponsive to initial hepatitis B vaccination, in celiac individuals. METHODS: We conducted our study on 58 celiac patients, vaccinated in the first year of life, whose blood analysis had showed the absence of protective hepatitis B virus (HBV) antibodies. All patients had received the last vaccine injection at least one year before study enrolment and they had been on a gluten free diet for at least 1 year. In all patients we randomly performed an HBV vaccine booster dose by ID or IM route. Thirty celiac patients were revaccinated with recombinant hepatitis B vaccine (Engerix B) 2 μg by the ID route, while 28 celiac patients were revaccinated with Engerix B 10 μg by the IM route. Four weeks after every booster dose, the anti-hepatitis B surface (HBs) antibody titer was measured by an enzyme-linked immune-adsorbent assay. We performed a maximum of three booster doses in patients with no anti-HBs antibodies after the first or the second vaccine dose. The cut off value for a negative anti-HBs antibody titer was 10 IU/L. Patients with values between 10 and 100 IU/L were considered "low responders" while patients with an antibody titer higher than 1000 IU/L were considered "high responders". RESULTS: No significant difference in age, gender, duration of illness, and years of gluten intake was found between the two groups. We found a high percentage of "responders" after the first booster dose (ID = 76.7%, IM = 78.6%) and a greater increase after the third dose (ID = 90%, IM = 96.4%) of vaccine in both groups. Moreover we found a significantly higher number of high responders (with an anti-HBs antibody titer > 1000 IU/L) in the ID (40%) than in the IM (7.1%) group, and this difference was evident after the first booster

  14. Molecular Identification of Paramecium bursaria Syngens and Studies on Geographic Distribution using Mitochondrial Cytochrome C Oxidase Subunit I (COI).

    PubMed

    Zagata, Patrycja; Greczek-Stachura, Magdalena; Tarcz, Sebastian; Rautian, Maria

    2015-01-01

    Paramecium bursaria is composed of five syngens that are morphologically indistinguishable but sexually isolated. The aim of the present study was to confirm by molecular methods (analyses of mitochondrial COI) the identification of P. bursaria syngens originating from different geographical locations. Phylograms constructed using both the neighbor-joining and maximum-likelihood methods based on a comparison of 34 sequences of P. bursaria strains and P. multimicronucleatum, P. caudatum and P.calkinsi strains used as outgroups revealed five clusters which correspond to results obtained previously by mating reaction. Our analysis shows the existence of 24 haplotypes for the COI gene sequence in the studied strains. The interspecies haplotype diversity was Hd = 0.967. We confirmed genetic differentiation between strains of P. bursaria and the occurrence of a correlation between geographical distribution and the correspondent syngen.

  15. Comparison of the toxicity profiles of ISIS 1082 and ISIS 2105, phosphorothioate oligonucleotides, following subacute intradermal administration in Sprague-Dawley rats.

    PubMed

    Henry, S P; Grillone, L R; Orr, J L; Bruner, R H; Kornbrust, D J

    1997-01-15

    The systemic toxicity of two phosphorothioate oligonucleotides specific for herpes simplex viruses (ISIS 1082) and human papiloma virus (ISIS 2105) were evaluated following repeated intradermal injections of vehicle control, 0.33, 2.17, or 21.7 mg/kg daily to Sprague-Dawley rats (10/sex/group) for 14 days. Animals were sacrificed 1 day after the last dose, except for a portion of the ISIS 1082-treated animals (5/sex/group) which were maintained for an additional 14-day recovery period. The profile of alterations noted for both compounds was very similar. Other than local signs of irritation at the site of injection, there were no clinical signs of toxicity or treatment-related mortality, but there was a slight decrease in body weight gain for the 21.7 mg/kg dose groups. Alterations in hematology parameters included dose-dependent thrombocytopenia and anemia. Alterations in serum chemistry parameters were suggestive of mild alterations in hepatic metabolism, with increases in liver transaminases and bilirubin, along with decreases in albumin and cholesterol. Both spleen and liver weights were significantly elevated in a dose-dependent fashion. Histopathological alterations noted in liver, kidney, lung, injection site skin, and spleen were characterized as perivascular and interstitial infiltrates of macrophages and monocytes. Additional microscopic alterations in the spleen included mild lymphoid hyperplasia (seen in lymph nodes as well), and extramedullary hematopoiesis. Treatment-related cytopenias were likely related to mild, focal hypocellularity in the bone marrow. Alterations in ISIS 1082-treated animals were only partially reversed following the 14-day treatment-free period. In conclusion, repeated intradermal administration of ISIS 1082 and ISIS 2105 produced a similar spectrum of toxicities, with liver, kidney, spleen, and bone marrow being identified as target tissues.

  16. Intradermal lymphoscintigraphy at rest and after exercise: a new technique for the functional assessment of the lymphatic system in patients with lymphoedema.

    PubMed

    Tartaglione, Girolamo; Pagan, Marco; Morese, Roberto; Cappellini, Giancarlo Antonini; Zappalà, Albina Rita; Sebastiani, Claudia; Paone, Giuseppe; Bernabucci, Valerio; Bartoletti, Roberto; Marchetti, Paolo; Marzola, Maria Cristina; Naji, Meeran; Rubello, Domenico

    2010-06-01

    The aim of this study was to evaluate the effect of implementing a new technique, intradermal injection lymphoscintigraphy, at rest and after muscular exercise on the functional assessment of the lymphatic system in a group of patients with delayed or absent lymph drainage. We selected 44 patients (32 women and 12 men; 15 of 44 with upper limb and 29 of 44 with lower limb lymphoedema). Thirty of 44 patients had bilateral limb lymphoedema and 14 of 44 had unilateral disease; 14 contralateral normal limbs were used as controls. Twenty-three patients had secondary lymphoedema after lymphadenectomy and the remaining 21 had idiopathic lymphoedema. Each of the 44 patients was injected with 50 MBq (0.3-0.4 ml) of (99m)Tc-albumin-nanocolloid, which was administered intradermally at the first interdigital space of the affected limb. Two planar static scans were performed using a low-energy general-purpose collimator (acquisition matrix 128 x 128, anterior and posterior views for 5 min), and in which drainage was slow or absent, patients were asked to walk or exercise for 2 min. A postexercise scan was then performed to monitor and record the tracer pathway and the tracer appearance time (TAT) in the inguinal or axillary lymph nodes. The postexercise scans showed that (i) 21 limbs (15 lower and six upper limbs) had accelerated tracer drainage and tracer uptake in the inguinal and/or axillary lymph nodes. Two-thirds of these showed lymph stagnation points; (ii) 27 limbs had collateral lymph drainage pathways; (iii) in 11 limbs, there was lymph drainage into the deeper lymphatic channels, with unusual uptake in the popliteal or antecubital lymph nodes; (iv) six limbs had dermal backflow; (v) three limbs did not show lymph drainage (TAT=not applicable). TAT=15 + or - 3 min, ranging from 12 to 32 min in limbs with lymphoedema versus 5 + or - 2 min, ranging from 1 to 12 min in the contralateral normal limbs (P<0.001). Intradermal injection lymphoscintigraphy gives a better

  17. Intradermal fractional booster dose of inactivated poliomyelitis vaccine with a jet injector in healthy adults.

    PubMed

    Soonawala, Darius; Verdijk, Pauline; Wijmenga-Monsuur, Alienke J; Boog, Claire J; Koedam, Patrick; Visser, Leo G; Rots, Nynke Y

    2013-08-12

    For global eradication of poliomyelitis, inactivated poliovirus vaccine (IPV) needs to become available in all countries. Using fractional-doses (reduced-doses) may impact affordability and optimize the utilization of the production capacity. Intradermal administration has the potential to lower the dose without reducing immunogenicity. A needle-free jet injector may be a reliable way to administer vaccines intradermally. The primary objective of this randomized controlled trial was to compare the immunogenicity and tolerability of fractional-dose intradermal IPV (Netherlands Vaccine Institute, NVI) booster vaccination administered with a jet injector (PharmaJet) to full-dose and fractional-dose intramuscular vaccination with a needle and syringe. Immunogenicity was assessed by comparing the differences in the post-vaccination log2 geometric mean concentrations of neutralizing antibodies (GMC) between the study groups. A total of 125 Dutch adult volunteers with a well-documented vaccination history were randomized to one of four groups: full-dose intramuscular needle (IM-NS-0.5), full-dose intramuscular jet injector (IM-JI-0.5), 1/5th dose intramuscular needle (IM-NS-0.1), 1/5th dose intradermal jet injector (ID-JI-0.1). Vaccination with the JI was less painful (87% no pain) than vaccination with a NS (60% no pain), but caused more transient erythema (JI 85%, NS 24%) and swelling (JI 50%, NS 5%). Intradermal vaccination caused less vaccination site soreness (ID 16%, IM 52%). At baseline all subjects had seroprotective antibody concentrations. After 28 days, GMC were slightly lower in the ID-JI-0.1 group than in the reference group (IM-NS-0.5). The differences were not statistically significant, but the stringent non-inferiority criterion (i.e. a difference of 1 serum dilution in the microneutralization assay) was not met. After one year, differences in GMC were no longer apparent. In contrast, intramuscular vaccination with a fractional dose administered with a

  18. Generation of a syngeneic orthotopic transplant model of prostate cancer metastasis

    PubMed Central

    Ellis, Leigh; Lehet, Kristin; Ku, ShengYu; Azabdaftari, Gissou; Pili, Roberto

    2014-01-01

    Progression to metastatic disease is the primary cause of mortality in men with prostate cancer (PCa). Mouse models which progress with spontaneous metastasis are limited. Such models would allow for extensive studies of molecular mechanisms of metastasis, and more definite pre- clinical therapy trials. Orthotopic murine models have been described; however a limiting biology of these models is their lack of an intact immune system. Within, we describe the development of an androgen sensitive and castrate resistant tractable orthotopic murine syngeneic (immune competent) model of prostate cancer. Both models develop primary tumors which spontaneously progress to metastatic disease in lymph tissue. These models will allow for more complete mechanistic and therapeutic studies in a short time period. PMID:25485289

  19. Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer.

    PubMed

    Pollard, Harvey B; Levine, Mark A; Eidelman, Ofer; Pollard, Morris

    2010-01-01

    The aim of this study was to test for the influence of ascorbic acid on tumorigenicity and metastases of implanted PAIII prostate cancer adenocarcinoma cells in syngeneic LW rats. Hormone-refractory prostate cancer PAIII cells were implanted subcutaneously into immunologically intact, Lobund-Wistar (LW) rats. Intraperitoneal pharmacological doses of ascorbic acid were administered each day for the ensuing 30 days. On the 40th day, animals were sacrificed. Local tumor weights were measured, and metastases were counted. At the end of the 40 day experimental period, the primary tumors were found to be significantly reduced in weight (p=0.026). In addition, sub-pleural lung metastases were even more profoundly reduced in number and size (p=0.009). Grossly enlarged ipsilateral lymph node metastases declined from 7 of 15 rats to 1 of 15 rats. Pharmacological doses of ascorbic acid suppress tumor growth and metastases in hormone-refractory prostate cancer.

  20. In vitro activation of murine Kupffer cells by lymphokines or endotoxins to lyse syngeneic tumor cells.

    PubMed Central

    Xu, Z. L.; Bucana, C. D.; Fidler, I. J.

    1984-01-01

    Murine Kupffer cells (RC) were isolated in sufficient number and purity to allow in vitro investigations of their tumoricidal capabilities. The identity of the adherent cells as KCs was established by morphologic, histochemical, and functional criteria. The yield of KCs varied from young (high) to old (low) mice but was not affected by the mouse strain. KCs activated in vitro by either endotoxins (lipopolysaccharide) or lymphokines were rendered highly cytotoxic against syngeneic melanoma or fibrosarcoma target cells. These studies indicate that KCs may indeed play a role in destruction of tumor cells in vivo and thus be important in host defense against developing hepatic cancer metastases. Images Figure 1 Figure 2 Figure 3 PMID:6391188

  1. Donor preconditioning with a calcineurin inhibitor improves outcome in rat syngeneic kidney transplantation.

    PubMed

    Shihab, Fuad S; Bennett, William M; Andoh, Takeshi F

    2009-02-15

    Ischemia-reperfusion injury (IRI) in the early posttransplant period affects immediate graft function and late allograft dysfunction. This study determines the influence of pharmacologic preconditioning with a calcineurin inhibitor on IRI in a syngeneic F344 rat kidney transplant model. Donor rats were pretreated with one dose of cyclosporine (10 mg/kg) or tacrolimus (1 mg/kg) administered at 24 hr or 7 days before being subjected to 2 hr of cold ischemia and then transplanted. Pharmacologic preconditioning significantly improved renal function, as assessed by serum creatinine and inulin clearance, and histologic score versus vehicle-treated rats. There were no differences between cyclosporine and tacrolimus in the measured outcomes. This renoprotective effect, although not complete, was seen with only one dose of calcineurin inhibitor, and the effect was sustained for at least 7 days before IRI. This approach may represent a viable pharmacologic intervention to decrease IRI at the time of organ transplantation.

  2. Periodontal Tissue Regeneration Using Syngeneic Adipose-Derived Stromal Cells in a Mouse Model.

    PubMed

    Lemaitre, Mathieu; Monsarrat, Paul; Blasco-Baque, Vincent; Loubières, Pascale; Burcelin, Rémy; Casteilla, Louis; Planat-Bénard, Valérie; Kémoun, Philippe

    2017-02-01

    Current treatment of periodontitis is still associated with a high degree of variability in clinical outcomes. Recent advances in regenerative medicine by mesenchymal cells, including adipose stromal cells (ASC) have paved the way to improved periodontal regeneration (PD) but little is known about the biological processes involved. Here, we aimed to use syngeneic ASCs for periodontal regeneration in a new, relevant, bacteria-induced periodontitis model in mice. Periodontal defects were induced in female C57BL6/J mice by oral gavage with periodontal pathogens. We grafted 2 × 10(5) syngeneic mouse ASCs expressing green fluorescent protein (GFP) (GFP+/ASC) within a collagen vehicle in the lingual part of the first lower molar periodontium (experimental) while carrier alone was implanted in the contralateral side (control). Animals were sacrificed 0, 1, 6, and 12 weeks after treatment by GFP+/ASC or vehicle graft, and microscopic examination, immunofluorescence, and innovative bio-informatics histomorphometry methods were used to reveal deep periodontium changes. From 1 to 6 weeks after surgery, GFP+ cells were identified in the periodontal ligament (PDL), in experimental sites only. After 12 weeks, cementum regeneration, the organization of PDL fibers, the number of PD vessels, and bone morphogenetic protein-2 and osteopontin expression were greater in experimental sites than in controls. Specific stromal cell subsets were recruited in the newly formed tissue in ASC-implanted periodontium only. These data suggest that ASC grafting in diseased deep periodontium, relevant to human pathology, induces a significant improvement of the PDL microenvironment, leading to a recovery of tooth-supporting tissue homeostasis. Stem Cells Translational Medicine 2017;6:656-665.

  3. Periodontal Tissue Regeneration Using Syngeneic Adipose-Derived Stromal Cells in a Mouse Model.

    PubMed

    Lemaitre, Mathieu; Monsarrat, Paul; Blasco-Baque, Vincent; Loubières, Pascale; Burcelin, Rémy; Casteilla, Louis; Planat-Bénard, Valérie; Kémoun, Philippe

    2016-09-16

    : Current treatment of periodontitis is still associated with a high degree of variability in clinical outcomes. Recent advances in regenerative medicine by mesenchymal cells, including adipose stromal cells (ASC) have paved the way to improved periodontal regeneration (PD) but little is known about the biological processes involved. Here, we aimed to use syngeneic ASCs for periodontal regeneration in a new, relevant, bacteria-induced periodontitis model in mice. Periodontal defects were induced in female C57BL6/J mice by oral gavage with periodontal pathogens. We grafted 2 × 10(5) syngeneic mouse ASCs expressing green fluorescent protein (GFP) (GFP+/ASC) within a collagen vehicle in the lingual part of the first lower molar periodontium (experimental) while carrier alone was implanted in the contralateral side (control). Animals were sacrificed 0, 1, 6, and 12 weeks after treatment by GFP+/ASC or vehicle graft, and microscopic examination, immunofluorescence, and innovative bio-informatics histomorphometry methods were used to reveal deep periodontium changes. From 1 to 6 weeks after surgery, GFP+ cells were identified in the periodontal ligament (PDL), in experimental sites only. After 12 weeks, cementum regeneration, the organization of PDL fibers, the number of PD vessels, and bone morphogenetic protein-2 and osteopontin expression were greater in experimental sites than in controls. Specific stromal cell subsets were recruited in the newly formed tissue in ASC-implanted periodontium only. These data suggest that ASC grafting in diseased deep periodontium, relevant to human pathology, induces a significant improvement of the PDL microenvironment, leading to a recovery of tooth-supporting tissue homeostasis.

  4. Expression of two H-2K genes, syngeneic and allogeneic, as a strategy for potentiating immune recognition of tumor cells.

    PubMed

    Mandelboim, O; Vadai, E; Feldman, M; Eisenbach, L

    1995-12-01

    Metastatic clones of some tumors manifest an impaired expression of class I major histocompatibility complex (MHC) antigens. High metastatic, low immunogenic Lewis lung carcinoma clones (C57BL-H-2b origin) express low levels of the H-2Kb MHC antigen. These cells metastasize spontaneously in C57BL/6J mice. Transfection of syngeneic or allogeneic H-2K genes converted such cells to the nonmetastatic state, but did not prevent the growth of the local tumors. Transfection of two H-2K genes, syngeneic and allogeneic, into the highly metastatic clone D122, resulted in reduction of the growth rates of the transfectants and protected the mice from D122 metastases. In contrast, cells transfected with a single class I gene (syngeneic or allogeneic) gave partial protection, or did not protect the mice at all from D122 metastases. The combination of syngeneic and allogeneic genes in the same tumor cell elevated the immunogenic properties of the expressing cells and potentiated the immune response as was demonstrated by in vitro cytotoxicity analysis and by limiting dilution cytotoxicity analysis. Increased immunogenicity by double transfection may constitute an effective therapeutic modality.

  5. Resistance to Oncolytic Myxoma Virus Therapy in Nf1−/−/Trp53−/− Syngeneic Mouse Glioma Models Is Independent of Anti-Viral Type-I Interferon

    PubMed Central

    Zemp, Franz J.; McKenzie, Brienne A.; Lun, Xueqing; Maxwell, Lori; Reilly, Karlyne M.; McFadden, Grant; Yong, V. Wee; Forsyth, Peter A.

    2013-01-01

    Despite promising preclinical studies, oncolytic viral therapy for malignant gliomas has resulted in variable, but underwhelming results in clinical evaluations. Of concern are the low levels of tumour infection and viral replication within the tumour. This discrepancy between the laboratory and the clinic could result from the disparity of xenograft versus syngeneic models in determining in vivo viral infection, replication and treatment efficacy. Here we describe a panel of primary mouse glioma lines derived from Nf1+/−Trp53+/− mice in the C57Bl/6J background for use in the preclinical testing of the oncolytic virus Myxoma (MYXV). These lines show a range of susceptibility to MYXV replication in vitro, but all succumb to viral-mediated cell death. Two of these lines orthotopically grafted produced aggressive gliomas. Intracranial injection of MYXV failed to result in sustained viral replication or treatment efficacy, with minimal tumour infection that was completely resolved by 7 days post-infection. We hypothesized that the stromal production of Type-I interferons (IFNα/β) could explain the resistance seen in these models; however, we found that neither the cell lines in vitro nor the tumours in vivo produce any IFNα/β in response to MYXV infection. To confirm IFNα/β did not play a role in this resistance, we ablated the ability of tumours to respond to IFNα/β via IRF9 knockdown, and generated identical results. Our studies demonstrate that these syngeneic cell lines are relevant preclinical models for testing experimental glioma treatments, and show that IFNα/β is not responsible for the MYXV treatment resistance seen in syngeneic glioma models. PMID:23762429

  6. Kinetics of Leptospira interrogans Infection in Hamsters after Intradermal and Subcutaneous Challenge

    PubMed Central

    Coutinho, Mariana L.; Matsunaga, James; Wang, Long-Chieh; de la Peña Moctezuma, Alejandro; Lewis, Michael S.; Babbitt, Jane T.; Aleixo, Jose Antonio G.; Haake, David A.

    2014-01-01

    Background Leptospirosis is a zoonosis caused by highly motile, helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions, and rapidly disseminate throughout the body. Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters, this challenge route does not represent a natural route of infection. Methodology/Principal Findings Here we describe the kinetics of disease and infection in hamster model of leptospirosis after subcutaneous and intradermal inoculation of Leptospira interrogans serovar Copenhageni, strain Fiocruz L1-130. Histopathologic changes in and around the kidney, including glomerular and tubular damage and interstitial inflammatory changes, began on day 5, and preceded deterioration in renal function as measured by serum creatinine. Weight loss, hemoconcentration, increased absolute neutrophil counts (ANC) in the blood and hepatic dysfunction were first noted on day 6. Vascular endothelial growth factor, a serum marker of sepsis severity, became elevated during the later stages of infection. The burden of infection, as measured by quantitative PCR, was highest in the kidney and peaked on day 5 after intradermal challenge and on day 6 after subcutaneous challenge. Compared to subcutaneous challenge, intradermal challenge resulted in a lower burden of infection in both the kidney and liver on day 6, lower ANC and less weight loss on day 7. Conclusions/Significance The intradermal and subcutaneous challenge routes result in significant differences in the kinetics of dissemination and disease after challenge with L. interrogans serovar Copenhageni strain Fiocruz L1-130 at an experimental dose of 2×106 leptospires. These results provide new information regarding infection kinetics in the hamster model of leptospirosis. PMID:25411782

  7. Cross-Linked Fluorescent Supramolecular Nanoparticles as Finite Tattoo Pigments with Controllable Intradermal Retention Times.

    PubMed

    Choi, Jin-Sil; Zhu, Yazhen; Li, Hongsheng; Peyda, Parham; Nguyen, Thuy Tien; Shen, Mo Yuan; Yang, Yang Michael; Zhu, Jingyi; Liu, Mei; Lee, Mandy M; Sun, Shih-Sheng; Yang, Yang; Yu, Hsiao-Hua; Chen, Kai; Chuang, Gary S; Tseng, Hsian-Rong

    2017-01-24

    Tattooing has been utilized by the medical community for precisely demarcating anatomic landmarks. This practice is especially important for identifying biopsy sites of nonmelanoma skin cancer (NMSC) due to the long interval (i.e., up to 3 months) between the initial diagnostic biopsy and surgical treatment. Commercially available tattoo pigments possess several issues, which include causing poor cosmesis, being mistaken for a melanocytic lesion, requiring additional removal procedures when no longer desired, and potentially inducing inflammatory responses. The ideal tattoo pigment for labeling of skin biopsy sites for NMSC requires (i) invisibility under ambient light, (ii) fluorescence under a selective light source, (iii) a finite intradermal retention time (ca. 3 months), and (iv) biocompatibility. Herein, we introduce cross-linked fluorescent supramolecular nanoparticles (c-FSNPs) as a "finite tattoo" pigment, with optimized photophysical properties and intradermal retention time to achieve successful in vivo finite tattooing. Fluorescent supramolecular nanoparticles encapsulate a fluorescent conjugated polymer, poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene] (MPS-PPV), into a core via a supramolecular synthetic approach. FSNPs which possess fluorescent properties superior to those of the free MPS-PPV are obtained through a combinatorial screening process. Covalent cross-linking of FSNPs results in micrometer-sized c-FSNPs, which exhibit a size-dependent intradermal retention. The 1456 nm sized c-FSNPs display an ideal intradermal retention time (ca. 3 months) for NMSC lesion labeling, as observed in an in vivo tattoo study. In addition, the c-FSNPs induce undetectable inflammatory responses after tattooing. We believe that the c-FSNPs can serve as a "finite tattoo" pigment to label potential malignant NMSC lesions.

  8. Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis

    PubMed Central

    Price, Dominique N.; Kusewitt, Donna F.; Lino, Christopher A.; McBride, Amber A.; Muttil, Pavan

    2016-01-01

    Bacille Calmette–Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0–80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical. PMID:27153120

  9. PO-34 - Optimal doses of tinzaparin to reduce both cancer-associated thrombosis and tumor growth in a mouse model of ectopic pancreatic syngeneic tumor.

    PubMed

    Panicot-Dubois, L; Mezouar, S; Plantureux, L; Crescence, L; Frère, C; Dubois, C

    2016-04-01

    In clinical studies, thromboprophylaxis with low-molecular-weight heparins (LMWHs) has been demonstrated to reduce the risk of venous thromboembolism and to improve outcomes in cancer patients. Moreover, preclinical models have previously suggested that LMWHs may also offer additional benefits through direct antitumor properties. However, the optimal doses of LMWHs that may prevent both cancer-related thrombosis and tumor development are yet unknown. The goal of this study was to determine the optimal doses of tinzaparin that may prevent both cancer-related thrombosis and tumor development in a syngeneic ectopic model of pancreatic cancer. The optimal doses of tinzaparin to generate a plasma anti-Xa activity >0.2IU/mL were determined in vivo following injection into wild type mice.The syngeneic ectopic model of cancer was induced in wild-type mice using the mouse pancreatic cancer cell line Panc02. Mice were injected daily with 200, 300IU/kg or 400IU/kg, or placebo from day 8 to 25 following tumor induction. Kinetics of thrombus formation and fibrin generation were determined in real time by digital real time intravital microscopy in mice bearing a tumor treated with tinzaparin or placebo. The growth of the tumor and the bleeding times were measured and compared in the different groups of mice. Plasma anti-Xa levels <0.2IU/mL were observed with tinzaparin doses ranging from 0 to 150IU/kg, whereas plasma anti-Xa activities >0.2IU/mL were obtained with >200IU/kg tinzaparin doses. At day 25 following tumor induction, the kinetics of thrombosis were not affected in mice treated with daily 200IU/kg tinzaparin compared to controls whereas it was strongly affected in mice treated with daily 300 and 400IU/kg tinzaparin. Interestingly, a significant decrease in tumor growth was observed in mice treated with 200, 300 and 400IU/kg tinzaparin in comparison to controls, with no significant difference between these groups. Bleeding times were similar to control mice in mice

  10. Sequential treatment with intradermal incision (intracision) and 2,940-nm Er:YAG laser for chicken pox scars.

    PubMed

    Lee, Sang Ju; Kim, Young Koo; Choi, Sun Young; Park, Kui Young; Seo, Seong Jun

    2014-01-01

    Boxcar scars, such as chicken pox scars, are round to oval depressions with sharply defined vertical edges. Subcision is a simple and safe procedure for treatment of atrophic and depressed scars, but boxcar scars are generally not eliminated by subcision. Intradermal incision technique (intracision) can treat chicken pox scars by untethering fibrotic strands, raising collagen synthesis, and having additional intradermal blood pocket formation. We have found that chicken pox scars further improve when intracision is followed by laser skin resurfacing.

  11. The effect of intradermal administration of inactive platelet-rich plasma on flap viability in rats.

    PubMed

    Orhan, Erkan; Uysal, Ahmet Çağrı; Başer, Engin; Keskin, Dürdane; Demiroğlu-Yakut, Çiğdem

    2017-04-01

    To evaluate the effect of inactive form of platelet rich plasma (PRP) on the flap viability. Thirty six rats were used. Rats were divided into six groups then 9x3 cm random pattern skin flaps were elevated from dorsum of all rats. For precluding vascularization from the base, a silicone layer was placed under the flap in groups 2(only flap+silicone), 4(saline+silicone) and 6(PRP+silicone). In groups 1(only flap), 2(only flap+silicone) nothing was done except flap surgery. In groups 3(saline) and 4(saline+silicone), saline was applied intradermally , in groups 5(PRP) and 6(PRP+silicone), inactive form of PRP which obtained from different 16 rats was applied intradermally, into certain points of flaps immediately after surgery. After 7 days flap necrosis ratio was measured in all groups. Mean necrosis rate in group 5(PRP) (16.05%) was statistically significantly lower than group 1(only flap) (31,93%) and group 3(saline) (30,43%) (p<0.001). Mean necrosis rate in group 6(PRP+silicone) (36.37%) was statistically significantly lower than group 2(only flap+silicone) (47.93%) and group 4(saline+silicone) (45.65%) (p<0.001). Intradermal inactive platelet rich plasma administration decreases flap necrosis so for skin application.

  12. Interstitial Fluid Pressure and Vascularity of Intradermal and Intramuscular Human Tumor Xenografts

    SciTech Connect

    Gulliksrud, Kristine; Galappathi, Kanthi; Rofstad, Einar K.

    2011-05-01

    Purpose: High interstitial fluid pressure (IFP) in tumors has been shown to be associated with poor prognosis. Mechanisms underlying the intertumor heterogeneity in IFP were investigated in this study. Methods and Materials: A-07 melanoma xenografts were transplanted intradermally or intramuscularly in BALB/c nu/nu mice. IFP was measured in the center of the tumors with a Millar catheter. Tumor blood perfusion and extracellular volume fraction were assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The necrotic fraction, vascular density, and vessel diameters of the tumors were determined by image analysis of histological preparations. Results: Significant intertumor heterogeneity in IFP, blood perfusion, and microvascular morphology was observed whether the tumors were transplanted intradermally or intramuscularly. High IFP was mainly a consequence of high resistance to blood flow caused by low vessel diameters in either transplantation site. IFP decreased with increasing blood perfusion in intradermal tumors and increased with increasing blood perfusion in intramuscular tumors, mainly because the morphology of the tumor microvasculature differed systematically between the two tumor models. Conclusion: The potential of DCE-MRI as a noninvasive method for assessing the IFP of tumors may be limited because any relationship between IFP and blood perfusion may differ with the tumor growth site.

  13. Intradermal Delivery of Antigens Enhances Specific IgG and Diminishes IgE Production: Potential Use for Vaccination and Allergy Immunotherapy

    PubMed Central

    Yasuda, Takuwa; Ura, Takehiro; Taniguchi, Masaru; Yoshida, Hisahiro

    2016-01-01

    Skin is protected by a tough but flexible multilayered barrier and is a front line for immune responses against invading particles. For many years now, skin has been a tissue where certain vaccines are injected for the prevention of infectious disease, however, the detailed mechanisms of the skin immune response are not yet well understood. Using thin and small injection needles, we carefully injected OVA into a restricted region of mouse skin, i.e., intradermal (ID), and examined the antibody response in comparison with subcutaneous (SC) injection or epicutaneous patch administration of OVA. Epicutaneous patches induced a high IgE response against OVA, but IgG production was low. High IgG production was induced by both ID and SC injection, moreover, ID injection induced higher IgG production without any adjutants. Furthermore, OVA-specific IgE production was diminished by ID injection. We found that ID injection could efficiently stimulate skin resident DCs, drive Th1-biased conditions and diminish IgE production. The ID injection response was regulated by Langerin+ dermal DCs, because OVA was taken up mainly by these cells and, after transiently deleting them, the IgE response was no longer diminished and IgG1 production was enhanced. We also tested whether ID injection might be an effective allergy treatment by attempting to inhibit ongoing IgE production in mice with experimentally induced high serum IgE levels. Multiple ID injections of OVA were shown to prevent elevation of serum OVA-specific IgE after repeated allergen challenge. In contrast, SC OVA injection could only transiently inhibit the OVA-specific IgE production. These findings indicated that ID injection results in higher induction of antigen-specific IgG, and thus may be useful for vaccine delivery with little or no adjuvant components. Moreover, the observed diminishment of IgE and induction of Th1-biased immune responses suggest that ID may be a useful injection route for allergy immunotherapy

  14. Bioluminescent Imaging of Genetically Selected Induced Pluripotent Stem Cell-Derived Cardiomyocytes after Transplantation into Infarcted Heart of Syngeneic Recipients

    PubMed Central

    Lepperhof, Vera; Polchynski, Olga; Kruttwig, Klaus; Brüggemann, Chantal; Neef, Klaus; Drey, Florian; Zheng, Yunjie; Ackermann, Justus P.; Choi, Yeong-Hoon; Wunderlich, Thomas F.; Hoehn, Mathias; Hescheler, Jürgen; Šarić, Tomo

    2014-01-01

    Cell loss after transplantation is a major limitation for cell replacement approaches in regenerative medicine. To assess the survival kinetics of induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) we generated transgenic murine iPSC lines which, in addition to CM-specific expression of puromycin N-acetyl-transferase and enhanced green fluorescent protein (EGFP), also constitutively express firefly luciferase (FLuc) for bioluminescence (BL) in vivo imaging. While undifferentiated iPSC lines generated by random integration of the transgene into the genome retained stable FLuc activity over many passages, the BL signal intensity was strongly decreased in purified iPS-CM compared to undifferentiated iPSC. Targeted integration of FLuc-expression cassette into the ROSA26 genomic locus using zinc finger nuclease (ZFN) technology strongly reduced transgene silencing in iPS-CM, leading to a several-fold higher BL compared to iPS-CM expressing FLuc from random genomic loci. To investigate the survival kinetics of iPS-CM in vivo, purified CM obtained from iPSC lines expressing FLuc from a random or the ROSA26 locus were transplanted into cryoinfarcted hearts of syngeneic mice. Engraftment of viable cells was monitored by BL imaging over 4 weeks. Transplanted iPS-CM were poorly retained in the myocardium independently of the cell line used. However, up to 8% of cells survived for 28 days at the site of injection, which was confirmed by immunohistological detection of EGFP-positive iPS-CM in the host tissue. Transplantation of iPS-CM did not affect the scar formation or capillary density in the periinfarct region of host myocardium. This report is the first to determine the survival kinetics of drug-selected iPS-CM in the infarcted heart using BL imaging and demonstrates that transgene silencing in the course of iPSC differentiation can be greatly reduced by employing genome editing technology. FLuc-expressing iPS-CM generated in this study will enable further

  15. The Effects of Pregabalin and the Glial Attenuator Minocycline on the Response to Intradermal Capsaicin in Patients with Unilateral Sciatica

    PubMed Central

    Sumracki, Nicole M.; Hutchinson, Mark R.; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond B.; Rolan, Paul

    2012-01-01

    Background Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. Aim This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. Methods/Results Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (−38% in affected leg, 95% CI for difference −19% to −52%). Both hand dominance and sex were significant covariates of response to capsaicin. Conclusions It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may

  16. Effect of Modified Alkaline Supplementation on Syngenic Melanoma Growth in CB57/BL Mice

    PubMed Central

    Spugnini, Enrico Pierluigi; Canese, Rossella; Gugliotta, Alessio; Fidanza, Stefano; Fais, Stefano

    2016-01-01

    Tumor extracellular acidity is a hallmark of malignant cancers. Thus, in this study we evaluated the effects of the oral administration of a commercially available water alkalizer (Basenpulver®) (BP) on tumor growth in a syngenic melanoma mouse model. The alkalizer was administered daily by oral gavage starting one week after tumor implantation in CB57/BL mice. Tumors were calipered and their acidity measured by in vivo MRI guided 31P MRS. Furthermore, urine pH was monitored for potential metabolic alkalosis. BP administration significantly reduced melanoma growth in mice; the optimal dose in terms of tolerability and efficacy was 8 g/l (p< 0.05). The in vivo results were supported by in vitro experiments, wherein BP-treated human and murine melanoma cell cultures exhibited a dose-dependent inhibition of tumor cell growth. This investigation provides the first proof of concept that systemic buffering can improve tumor control by itself and that this approach may represent a new strategy in prevention and/or treatment of cancers. PMID:27447181

  17. Fatal Meningitis in Swine after Intrathecal Administration of Adeno-associated Virus Expressing Syngeneic Interleukin-10.

    PubMed

    Unger, Mark D; Pleticha, Josef; Collins, James E; Armien, Anibal G; Brazzell, Jennifer L; Newman, Laura K; Heilmann, Lukas F; Scholz, Jodi A; Maus, Timothy P; Beutler, Andreas S

    2017-08-01

    Interleukin-10 (IL-10) delivered by intrathecal (i.t.) gene vectors is a candidate investigational new drug (IND) for several chronic neurological disorders such as neuropathic pain. We performed a preclinical safety study of IL-10. A syngeneic large animal model was used delivering porcine IL-10 (pIL-10) to the i.t. space in swine by adeno-associated virus serotype 8 (AAV8), a gene vector that was previously found to be nontoxic in the i.t. space. Unexpectedly, animals became ill, developing ataxia, seizures, and an inability to feed and drink, and required euthanasia. Necropsy demonstrated lymphocytic meningitis without evidence of infection in the presence of normal laboratory findings for body fluids and normal histopathology of peripheral organs. Results were replicated in a second animal cohort by a team of independent experimenters. An extensive infectious disease and neuropathology workup consisting of comprehensive testing of tissues and body fluids in a specialized research veterinary pathology environment did not identify a pathogen. These observations raise the concern that i.t. IL-10 therapy may not be benign, that previously used xenogeneic models testing the human homolog of IL-10 may not have been sensitive enough to detect toxicity, and that additional preclinical studies may be needed before clinical testing of IL-10 can be considered. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  18. Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

    PubMed

    Fan, Z; Enjoji, K; Tigges, J C; Toxavidis, V; Tchipashivili, V; Gong, W; Strom, T B; Koulmanda, M

    2014-12-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation.

    PubMed

    Wen, Yanting; Ouyang, Jian; Yang, Rong; Chen, Junhao; Liu, Yong; Zhou, Xiaojun; Burt, Richard K

    2008-09-19

    Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n=20) and recipients (n=20). Compared to streptozocin-treated mice not receiving transplantation, syngeneic bone marrow transplantation (syn-BMT) from a streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10 after diabetes onset), can reverse hyperglycemia without relapse (P<0.001), maintain normal blood insulin levels (P<0.001), and preserve islet cell mass. Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of Tregs in spleens (P<0.01), increased Foxp3 mRNA expression (P<0.01) and increased Foxp3 protein expression (P<0.05). This diabetic-remission-inducing effect occurred in mice receiving bone marrow from either streptozocin-treated diabetic or non-diabetic normal donors. We conclude that autologous HSCT remission of diabetes is more than transient immune suppression, and is capable of prolonged remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs.

  20. Bone Marrow Derived Hematopoietic Stem and Progenitor Cells Infiltrate Allogeneic and Syngeneic Transplants

    PubMed Central

    Fan, Z.; Enjoji, K.; Tigges, J. C.; Toxavidis, V.; Tchipashivili, V.; Gong, W.; Strom, T. B.; Koulmanda, M.

    2015-01-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineagenegative Sca-1+cKit+ (“LSK”) cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic “LSK” HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, “LSK” HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intra-medullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs. PMID:25387427

  1. Extrahepatic islet transplantation with microporous polymer scaffolds in syngeneic mouse and allogeneic porcine models.

    PubMed

    Gibly, Romie F; Zhang, Xiaomin; Graham, Melanie L; Hering, Bernhard J; Kaufman, Dixon B; Lowe, William L; Shea, Lonnie D

    2011-12-01

    Intraportal transplantation of islets has successfully treated select patients with type 1 diabetes. However, intravascular infusion and the intrahepatic site contribute to significant early and late islet loss, yet a clinical alternative has remained elusive. We investigated non-encapsulating, porous, biodegradable polymer scaffolds as a vehicle for islet transplantation into extrahepatic sites, using syngeneic mouse and allogeneic porcine models. Scaffold architecture was modified to enhance cell infiltration leading to revascularization of the islets with minimal inflammatory response. In the diabetic mouse model, 125 islets seeded on scaffolds implanted into the epididymal fat pad restored normoglycemia within an average of 1.95 days and transplantation of only 75 islets required 12.1 days. Increasing the pore size to increase islet-islet interactions did not significantly impact islet function. The porcine model was used to investigate early islet engraftment. Increasing the islet seeding density led to a greater mass of engrafted islets, though the efficiency of islet survival decreased. Transplantation into the porcine omentum provided greater islet engraftment than the gastric submucosa. These results demonstrate scaffolds support murine islet transplantation with high efficiency, and feasibility studies in large animals support continued pre-clinical studies with scaffolds as a platform to control the transplant microenvironment.

  2. Multiple functions of CXCL12 in a syngeneic model of breast cancer

    PubMed Central

    2010-01-01

    Background A growing body of work implicates chemokines, in particular CXCL12 and its receptors, in the progression and site-specific metastasis of various cancers, including breast cancer. Various agents have been used to block the CXCL12-CXCR4 interaction as a means of inhibiting cancer metastasis. However, as a potent chemotactic factor for leukocytes, CXCL12 also has the potential to enhance anti-cancer immunity. To further elucidate its role in breast cancer progression, CXCL12 and its antagonist CXCL12(P2G) were overexpressed in the syngeneic 4T1.2 mouse model of breast carcinoma. Results While expression of CXCL12(P2G) significantly inhibited metastasis, expression of wild-type CXCL12 potently inhibited both metastasis and primary tumor growth. The effects of wild-type CXCL12 were attributed to an immune response characterized by the induction of CD8+ T cell activity, enhanced cell-mediated cytotoxicity, increased numbers of CD11c+ cells in the tumor-draining lymph nodes and reduced accumulation of myeloid-derived suppressor cells in the spleen. Conclusions This study highlights the need to consider carefully therapeutic strategies that block CXCL12 signaling. Therapies that boost CXCL12 levels at the primary tumor site may prove more effective in the treatment of metastatic breast cancer. PMID:20849618

  3. Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans.

    PubMed

    Borggren, Marie; Nielsen, Jens; Bragstad, Karoline; Karlsson, Ingrid; Krog, Jesper S; Williams, James A; Fomsgaard, Anders

    2015-01-01

    The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine expressed by next-generation vectors. These new vectors can improve gene expression, but they are also efficiently produced on large scales and comply with regulatory guidelines by avoiding antibiotic resistance genes. In addition, a new needle-free delivery of the vaccine, convenient for mass vaccinations, was compared with intradermal needle injection followed by electroporation. We report that when our DNA vaccine is expressed by the new vectors and delivered to the skin with the needle-free device in the rabbit model, it can elicit an antibody response with the same titers as a conventional vector with intradermal electroporation. The needle-free delivery is already in use for traditional protein vaccines in pigs but should be considered as a practical alternative for the mass administration of broadly protective influenza DNA vaccines.

  4. Investigation on the effects of ciclosporin (Atopica) on intradermal test reactivity and allergen-specific immunoglobulin (IgE) serology in atopic dogs.

    PubMed

    Goldman, Candice; Rosser, Edmund; Petersen, Annette; Hauptman, Joe

    2010-08-01

    The ability to use ciclosporin (Atopica®: Novartis Animal Health, Greensboro, NC, USA) prior to intradermal testing (IDT) would help avoid exacerbation of clinical disease that can be associated with drug withdrawal. This study evaluated the effects of 30 days of administration of ciclosporin at a dose of 5 mg/kg once daily on IDT reactivity (immediate phase reactions) in a group of dogs with atopic dermatitis (AD) with initial positive IDT reactions. 16 dogs diagnosed with AD were included in the study. Eight dogs (group A) were treated with ciclosporin orally at 5 mg/kg once daily for 30 days. Eight dogs (group P) were treated with a placebo orally once daily for 30 days. IDT was performed at day 0 and day 30 on all dogs enrolled using a standardized panel of 45 aqueous allergens (Greer Laboratories, Lenoir, NC, USA) appropriate to our geographical region. IDT reactivity was assessed by both subjective and objective methods at 15 min post-intradermal injection. Serum for allergen-specific immunoglobulin (IgE) serology was obtained at day 0 and day 30. The study was designed as a double-blinded, placebo-controlled, cross-over study. Data were analysed using a split-plot analysis of variance with the grouping factor of treatment and the repeat factor of time (SAS System for Windows). At week 4, ciclosporin did not have a statistically significant effect on IDT reactivity or serology results. It therefore appears that, no withdrawal is recommended to evaluate immediate phase reactions.

  5. Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance

    PubMed Central

    Berteau, Cecile; Filipe-Santos, Orchidée; Wang, Tao; Rojas, Humberto E; Granger, Corinne; Schwarzenbach, Florence

    2015-01-01

    Aim The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC) injection pain tolerance. Methods The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8–10, and 15–20 cP) combined with two different injection flow rates (0.02 and 0.3 mL/s). All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS) (0 mm/no pain, 100 mm/extreme pain). The location and depth of the injected fluid was assessed through 2D ultrasound echography images. Results Viscosity levels had significant impact on perceived injection pain (P=0.0003). Specifically, less pain was associated with high viscosity (VAS =12.6 mm) than medium (VAS =16.6 mm) or low (VAS =22.1 mm) viscosities, with a significant difference between high and low viscosities (P=0.0002). Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89). Slow (0.02 mL/s) or fast (0.30 mL/s) injection rates also showed no significant impact on perceived pain during SC injection (P=0.79). In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers. Conclusion The results of this study suggest that solutions of up to 3 mL and up to 15–20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High viscosity injections were shown to be the most tolerated, whereas injection volume and flow rates did not impact perceived pain. PMID:26635489

  6. Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance.

    PubMed

    Berteau, Cecile; Filipe-Santos, Orchidée; Wang, Tao; Rojas, Humberto E; Granger, Corinne; Schwarzenbach, Florence

    2015-01-01

    The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC) injection pain tolerance. The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8-10, and 15-20 cP) combined with two different injection flow rates (0.02 and 0.3 mL/s). All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS) (0 mm/no pain, 100 mm/extreme pain). The location and depth of the injected fluid was assessed through 2D ultrasound echography images. Viscosity levels had significant impact on perceived injection pain (P=0.0003). Specifically, less pain was associated with high viscosity (VAS =12.6 mm) than medium (VAS =16.6 mm) or low (VAS =22.1 mm) viscosities, with a significant difference between high and low viscosities (P=0.0002). Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89). Slow (0.02 mL/s) or fast (0.30 mL/s) injection rates also showed no significant impact on perceived pain during SC injection (P=0.79). In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers. The results of this study suggest that solutions of up to 3 mL and up to 15-20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High viscosity injections were shown to be the most tolerated, whereas injection volume and flow rates did not impact perceived pain.

  7. ZnO Nano-Rod Devices for Intradermal Delivery and Immunization.

    PubMed

    Nayak, Tapas R; Wang, Hao; Pant, Aakansha; Zheng, Minrui; Junginger, Hans; Goh, Wei Jiang; Lee, Choon Keong; Zou, Shui; Alonso, Sylvie; Czarny, Bertrand; Storm, Gert; Sow, Chorng Haur; Lee, Chengkuo; Pastorin, Giorgia

    2017-06-15

    Intradermal delivery of antigens for vaccination is a very attractive approach since the skin provides a rich network of antigen presenting cells, which aid in stimulating an immune response. Numerous intradermal techniques have been developed to enhance penetration across the skin. However, these methods are invasive and/or affect the skin integrity. Hence, our group has devised zinc oxide (ZnO) nano-rods for non-destructive drug delivery. Chemical vapour deposition was used to fabricate aligned nano-rods on ZnO pre-coated silicon chips. The nano-rods' length and diameter were found to depend on the temperature, time, quality of sputtered silicon chips, etc. Vertically aligned ZnO nano-rods with lengths of 30-35 µm and diameters of 200-300 nm were selected for in vitro human skin permeation studies using Franz cells with Albumin-fluorescein isothiocyanate (FITC) absorbed on the nano-rods. Fluorescence and confocal studies on the skin samples showed FITC penetration through the skin along the channels formed by the nano-rods. Bradford protein assay on the collected fluid samples indicated a significant quantity of Albumin-FITC in the first 12 h. Low antibody titres were observed with immunisation on Balb/c mice with ovalbumin (OVA) antigen coated on the nano-rod chips. Nonetheless, due to the reduced dimensions of the nano-rods, our device offers the additional advantage of excluding the simultaneous entrance of microbial pathogens. Taken together, these results showed that ZnO nano-rods hold the potential for a safe, non-invasive, and painless intradermal drug delivery.

  8. Strategic use of serology for the diagnosis of bovine tuberculosis after intradermal skin testing.

    PubMed

    Casal, Carmen; Díez-Guerrier, Alberto; Álvarez, Julio; Rodriguez-Campos, Sabrina; Mateos, Ana; Linscott, Richard; Martel, Edmond; Lawrence, John C; Whelan, Clare; Clarke, John; O'Brien, Amanda; Domínguez, Lucas; Aranaz, Alicia

    2014-06-04

    Diagnostic tests based on cell-mediated immunity are used in programmes for eradication of bovine tuberculosis (Mycobacterium bovis). Serological assays could be applied as ancillary methods to detect infected animals. Our objective was to evaluate two serological techniques: M. bovis Ab Test (IDEXX, USA) and Enferplex™ TB assay (Enfer, Ireland) in animals tested simultaneously with the single and comparative intradermal tests and the interferon-gamma assay. This work was performed at two stages. First, a preliminary panel of samples collected prior to intradermal tests from tuberculosis-free (n=60) and M. bovis-infected herds (n=78) was assayed, obtaining high specificity: 100% (M. bovis Ab Test) and 98.3% (Enferplex TB assay) but low sensitivity (detection of M. bovis infected animals): 23.9% (M. bovis Ab Test) and 32.6% (Enferplex TB assay). Subsequently, the use of serological techniques was further studied in two herds with M. bovis infection (n=77) using samples collected prior to, and 72 h and 15 days after PPD inoculation. The highest level of detection of infected animals for serology was achieved at 15 days post-intradermal tests taking advantage of the anamnestic effect: 70.4% and 85.2% in herd A, and 66.7% and 83.3% in herd B, using M. bovis Ab Test and Enferplex TB assay, respectively. Quantitative results (average values obtained with M. bovis Ab Test ELISA and degree of positivity obtained with Enferplex TB assay) were higher in animals showing lesions compatible with tuberculosis. No significant differences were observed in the number of confirmed infected animals detected with either serological technique. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. ZnO Nano-Rod Devices for Intradermal Delivery and Immunization

    PubMed Central

    Nayak, Tapas R.; Wang, Hao; Pant, Aakansha; Zheng, Minrui; Junginger, Hans; Goh, Wei Jiang; Lee, Choon Keong; Zou, Shui; Alonso, Sylvie; Czarny, Bertrand; Storm, Gert; Sow, Chorng Haur; Lee, Chengkuo; Pastorin, Giorgia

    2017-01-01

    Intradermal delivery of antigens for vaccination is a very attractive approach since the skin provides a rich network of antigen presenting cells, which aid in stimulating an immune response. Numerous intradermal techniques have been developed to enhance penetration across the skin. However, these methods are invasive and/or affect the skin integrity. Hence, our group has devised zinc oxide (ZnO) nano-rods for non-destructive drug delivery. Chemical vapour deposition was used to fabricate aligned nano-rods on ZnO pre-coated silicon chips. The nano-rods’ length and diameter were found to depend on the temperature, time, quality of sputtered silicon chips, etc. Vertically aligned ZnO nano-rods with lengths of 30–35 µm and diameters of 200–300 nm were selected for in vitro human skin permeation studies using Franz cells with Albumin-fluorescein isothiocyanate (FITC) absorbed on the nano-rods. Fluorescence and confocal studies on the skin samples showed FITC penetration through the skin along the channels formed by the nano-rods. Bradford protein assay on the collected fluid samples indicated a significant quantity of Albumin-FITC in the first 12 h. Low antibody titres were observed with immunisation on Balb/c mice with ovalbumin (OVA) antigen coated on the nano-rod chips. Nonetheless, due to the reduced dimensions of the nano-rods, our device offers the additional advantage of excluding the simultaneous entrance of microbial pathogens. Taken together, these results showed that ZnO nano-rods hold the potential for a safe, non-invasive, and painless intradermal drug delivery. PMID:28617335

  10. Induced pluripotent stem cell-derived gamete-associated proteins incite rejection of induced pluripotent stem cells in syngeneic mice.

    PubMed

    Kim, Eun-Mi; Manzar, Gohar; Zavazava, Nicholas

    2017-02-10

    The safety of induced pluripotent stem cells (iPSCs) in autologous recipients has been questioned after iPSCs, but not embryonic stem cells (ESCs), were reported to be rejected in syngeneic mice. This important topic has remained controversial because there has not been a mechanistic explanation for this phenomenon. Here, we hypothesize that iPSCs, but not ESCs, readily differentiate into gamete-forming cells that express meiotic antigens normally found in immune-privileged gonads. Because peripheral blood T cells are not tolerized to these antigens in the thymus, gamete-associated-proteins (GAPs) sensitize T cells leading to rejection. Here, we provide evidence that GAPs expressed in iPSC teratomas, but not in ESC teratomas, are responsible for the immunological rejection of iPSCs. Furthermore, silencing the expression of Stra8, 'the master regulator of meiosis', in iPSCs, using short hairpin RNA led to significant abrogation of the rejection of iPSCs, supporting our central hypothesis that GAPs expressed after initiation of meiosis in iPSCs were responsible for rejection. In contrast to iPSCs, iPSC-derivatives, such as haematopoietic progenitor cells, are able to engraft long-term into syngeneic recipients because they no longer express GAPs. Our findings, for the first time, provide a unifying explanation of why iPSCs, but not ESCs, are rejected in syngeneic recipients, ending the current controversy on the safety of iPSCs and their derivatives.

  11. Limited Functional Effects of Subacute Syngeneic Bone Marrow Stromal Cell Transplantation After Rat Spinal Cord Contusion Injury.

    PubMed

    Sandner, Beatrice; Ciatipis, Mareva; Motsch, Melanie; Soljanik, Irina; Weidner, Norbert; Blesch, Armin

    2016-01-01

    Cell transplantation might be one means to improve motor, sensory, or autonomic recovery after traumatic spinal cord injury (SCI). Among the different cell types evaluated to date, bone marrow stromal cells (BMSCs) have received considerable interest due to their potential neuroprotective properties. However, uncertainty exists whether the efficacy of BMSCs after intraspinal transplantation justifies an invasive procedure. In the present study, we analyzed the effect of syngeneic BMSC transplantation following a moderate to severe rat spinal cord injury. Adult Fischer 344 rats underwent a T9 contusion injury (200 kDy) followed by grafting of GFP-expressing BMSCs 3 days postinjury. Animals receiving a contusion injury without cellular grafts or an injury followed by grafts of syngeneic GFP-expressing fibroblasts served as control. Eight weeks posttransplantation, BMSC-grafted animals showed only a minor effect in one measure of sensorimotor recovery, no significant differences in tissue sparing, and no changes in the recovery of bladder function compared to both control groups in urodynamic measurements. Both cell types survived in the lesion site with fibroblasts displaying a larger graft volume. Thus, contrary to some reports using allogeneic or xenogeneic transplants, subacute intraparenchymal grafting of syngeneic BMSCs has only a minor effect on functional recovery.

  12. Serological, intradermal and live flea challenge tests in the assessment of hypersensitivity to flea antigens in cats (Felis domesticus).

    PubMed

    Bond, Ross; Hutchinson, Melanie J; Loeffler, Anette

    2006-09-01

    The results of intradermal testing with three commercial flea antigens and a serological test for IgE antibodies to flea antigens were compared with live flea challenge in cats. Eight control cats with no prior flea exposure had negative serological test and flea challenge results. By contrast, 17 out of 27 cats with previous flea exposure showed immediate reactivity to flea challenge; reactivity at 6, 24 and 48 h after flea exposure was noted in 12, 16 and 21 cats, respectively. Seventeen of these cats had positive serological test results. Seven cats showed immediate intradermal test reactions to the ARTU allergen, six reacted to the Biophady allergen, and six reacted to the Greer allergen. Intradermal test reactivity was less frequent at the other time points. Using the results of the flea challenge as the 'gold standard' for the presence or absence of sensitisation to fleas, the sensitivity and specificity of the serological test was 0.88 and 0.77, respectively. Sensitivities of the intradermal tests at the four time points ranged from 0 to 0.33, whereas the specificities ranged from 0.78 to 1.0. Live flea challenge is better able to detect cats with hypersensitivity to fleas than either intradermal or serological testing.

  13. Intradermal alpha1-antitrypsin therapy avoids fatal anaphylaxis, prevents type 1 diabetes and reverses hyperglycaemia in the NOD mouse model of the disease.

    PubMed

    Ma, H; Lu, Y; Li, H; Campbell-Thompson, M; Parker, M; Wasserfall, C; Haller, M; Brantly, M; Schatz, D; Atkinson, M; Song, S

    2010-10-01

    Human alpha1-antitrypsin (hAAT) gene therapy prevents type 1 diabetes in a NOD mouse model of diabetes. However, repeated i.p. injections of hAAT into NOD mice leads to fatal anaphylaxis. The aim of the study was to determine if an alternative route of administration avoids anaphylaxis and allows evaluation of hAAT's potential for diabetes prevention and reversal. We also sought to determine if the addition of granulocyte colony-stimulating factor (G-CSF), augments hAAT's capacity to prevent or reverse disease in the NOD mice. To evaluate hAAT pharmacokinetics, serum hAAT levels were monitored in NOD mice receiving a single dose (2 mg) of hAAT by i.p., s.c. or i.d. injection. For studies of type 1 diabetes prevention and reversal, mice received i.d. hAAT (2 mg/mouse/3 days) for 8 or 10 weeks or hAAT and G-CSF (i.p., 6 microg/day) for 6 weeks. Blood glucose determinations, glucose tolerance testing and insulin tolerance tests were performed. Both i.p. and s.c. injections resulted in fatal anaphylaxis. The i.d. injection avoided anaphylaxis and i.d. injection of hAAT into 11-week-old NOD mice prevented disease (p = 0.005, AAT vs PBS at 40 weeks of age). Treatment of diabetic NOD mice with hAAT or hAAT plus G-CSF provided long-term (at least 100 days) reversal of diabetes in 50% of treated animals. G-CSF did not enhance the reversal rates of hAAT. Glucose tolerance and insulin levels were normalised in mice with hAAT prevention and reversal. Intradermal hAAT prevents and reverses disease in a NOD mouse model of type 1 diabetes without inducing anaphylaxis.

  14. Modulation of Human Allogeneic and Syngeneic Pluripotent Stem Cells and Immunological Implications for Transplantation

    PubMed Central

    Sackett, S.D.; Brown, M.E.; Tremmel, D.M.; Ellis, T.; Burlingham, W.J.; Odorico, J.S.

    2016-01-01

    Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. PMID:26970668

  15. Novel syngeneic pseudo-orthotopic prostate cancer model: vascular, mitotic and apoptotic responses to castration.

    PubMed

    Frost, Gregory I; Lustgarten, Joseph; Dudouet, Brigitte; Nyberg, Linda; Hartley-Asp, Beryl; Borgström, Per

    2005-01-01

    We describe a novel syngeneic "pseudo-orthotopic" in vivo model of prostate cancer progression. Our model uses the dorsal skinfold chamber technique with fluorescence video microscopy and TRAMP-C2 tumor cells. The cells were transfected with a histone H2B-GFP fusion protein, permitting real-time measurement of tumor size, as well as mitotic and apoptotic indices. To generate a "pseudo-orthotopic" milieu, pieces of prostate tissue (10-15 mm2) from donor mice were implanted into the chambers of C57BL/6 mice. The prostate tissue grafted into the chambers retained its native vasculature, as determined by transplantation of prostate tissue from GFP transgenic mice. TRAMP-C2 prostate cancer tumor spheroids (25,000 cells) were implanted in the chamber. Without prostate tissue, TRAMP-C2 prostate tumors were poorly angiogenic, displayed low mitotic and apoptotic indices (0.7 x 10(-4)), and no significant tumor growth could be detected. TRAMP-C2 tumors growing on transplanted prostate tissue in the chamber on the other hand had mitotic indices in the order of 1.6 x 10(-4) and apoptotic indices in the order of 0.8 x 10(-4). Furthermore, tumors with stroma were highly angiogenic, and were fully vascularized within 7-10 days. During a 4-week observation period, the number of tumor cells increased by nearly 300%. We used the model to study the effects of surgical castration. The most profound response was a rapid vascular regression of the tumor vasculature. Castration also increased apoptotic indices within the tumor without significant changes in mitosis. This model may be utilized for the rapid analysis of new therapeutic candidates against prostate cancer.

  16. Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines when administered by intradermal route

    PubMed Central

    Bilagumba, Gangaboraiah; Ravish, Haradanahalli Shankarappa; Narayana, Hanumanthappa Ashwath Doddabele

    2010-01-01

    The metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986–2009) was used for metaanalysis. The vaccines studied were purified chick embryo cell vaccine (Rabipur, India and Germany), purified vero cell rabies vaccine (Verorab, France; Indirab, India) and human diploid cell vaccine (MIRV, France). The potency of these vaccines varied from 0.55 IU to 2.32 IU per intradermal dose of 0.1 ml per site. The vaccines were administered to 1,011 subjects comprising of 19 cohorts and using five different ID regimens. The immunogenicity was measured by assays of rabies virus neutralizing antibody (RVNA) titres using rapid fluorescent focus inhibition test (RFFIT) [15 cohorts] and mouse neutralization test (MNT) [4 cohorts]. The statistical analysis of the data was done by Karl Pearson's correlation coefficient to measure the relationship between antigenicity and immunogenicity. It was revealed that, there was no significant linear relationship between antigenicity and immunogenicity of rabies vaccines when administered by intradermal route (p > 0.230 and p > 0.568). PMID:20523131

  17. Hepatitis B vaccine by intradermal route in non responder patients: An update

    PubMed Central

    Filippelli, Martina; Lionetti, Elena; Gennaro, Alessia; Lanzafame, Angela; Arrigo, Teresa; Salpietro, Carmelo; La Rosa, Mario; Leonardi, Salvatore

    2014-01-01

    Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined “no responders”. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type I diabetes mellitus, down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013. PMID:25132754

  18. The results of intradermal skin tests (IDST) in dogs with atopic dermatitis from the Lublin voivodeship.

    PubMed

    Taszkun, I

    2011-01-01

    The purpose of this study was to assess the positive immediate reactions received from intradermal skin tests (IDST) which confirmed the presence of IgE-dependent hypersensitivity in dogs with atopic dermatitis, which were patients of the Dermatology Consulting Section at the University of Life Sciences in Lublin between 2007 and 2009. Intradermal skin tests were performed on 142 dogs (72 females and 70 males) from the Lublin voivodeship of different breeds ranging in age from 1 to 6 years (average 2.8 years). The allergen set used in this study was the Artuvetrin Test (ARTU Biologicals Europe B.V, Holland). The owners of 84 dogs observed the presence of skin lesions all year round regardless of season, while 58 dog owners noted them only in spring and summer. Most immediate positive reactions were ascertained from mite allergens (70.61%), fewer from pollen allergens (19.55%), and the fewest from animal (4.15%) and mould allergens (1.66%). Immediate positive reactions for a flea allergen (4.03% of all positive reactions) were also ascertained. In 98.6% of dogs polysensitization was found.

  19. A comparison of a new skin closure device and intradermal sutures in the closure of full-thickness surgical incisions.

    PubMed

    Richter, Dirk; Stoff, Alexander; Ramakrishnan, Venkat; Exner, Klaus; Jernbeck, Jan; Blondeel, Phillip N

    2012-10-01

    A novel topical skin adhesive system was developed to close the outermost layer of skin in an expeditious manner. To determine its clinical utility, a clinical investigation was undertaken to demonstrate equivalence of a new adhesive skin closure system (Prineo Skin Closure System) to intradermal sutures in wound closure. The investigation included 83 patients who underwent elective abdominoplasty, circumferential body lift procedures, and breast reconstruction with deep inferior epigastric perforator flaps. Incisions were divided in half, and each half was randomized to wound closure with the new skin closure system, including a pressure-sensitive adhesive mesh tape for wound edge approximation and next-generation cyanoacrylate or intradermal sutures. Postoperative evaluations took place at 24 hours, 7 days, 12 to 25 days, 90 days, 6 months, and 12 months. The new skin closure system was found to be equivalent to intradermal sutures for the continuous approximation of wounds. The upper limit of the two-sided 90 percent confidence interval for difference in proportions was 10.9 percent. The mean time to closure for the new skin closure system was 1.46 minutes, approximately 5 minutes faster than that for intradermal sutures (p < 0.0001). Both treatments had similar incision healing and cosmetic outcomes. No quantitative or qualitative differences of clinical significance were evident between the treatment groups. The Prineo Skin Closure System can be considered equivalent to intradermal sutures for full-thickness surgical incisions with regard to safety and effectiveness. The ease and speed of application contribute to shortened operative times (4.5 times faster than intradermal sutures).

  20. The intratumoral distribution of radiolabeled 177Lu-BR96 monoclonal antibodies changes in relation to tumor histology over time in a syngeneic rat colon carcinoma model.

    PubMed

    Örbom, Anders; Eriksson, Sophie E; Elgström, Erika; Ohlsson, Tomas; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik

    2013-08-01

    The therapeutic effect of radioimmunotherapy depends on the distribution of the absorbed dose in relation to viable cancer cells within the tumor, which in turn is a function of the activity distribution. The aim of this study was to investigate the distribution of (177)Lu-DOTA-BR96 monoclonal antibodies targeting the Lewis Y antigen over 7 d using a syngeneic rat model of colon carcinoma. Thirty-eight tumor-bearing rats were intravenously given 25 or 50 MBq of (177)Lu-DOTA-BR96 per kilogram of body weight and were sacrificed 2, 8, 24, 48, 72, 96, 120, or 168 h after injection, with activity measured in blood and tumor samples. Adjacent cryosections of each tumor were analyzed in 3 ways: imaging using a silicon-strip detector for digital autoradiography, staining for histologic characterization, or staining to determine the distribution of the antigen, vasculature, and proliferating cells using immunohistochemistry. Absorbed-dose rate distribution images at the moment of sacrifice were calculated using the activity distribution and a point-dose kernel. The correlations between antigen expression and both activity uptake and absorbed-dose rate were calculated for several regions of interest in each tumor. Nine additional animals with tumors were given unlabeled antibody to evaluate possible immunologic effects. At 2-8 h after injection, activity was found in the tumor margins; at 24 h, in viable antigen-expressing areas within the tumor; and at 48 h and later, increasingly in antigen-negative areas of granulation tissue. The correlation between antigen expression and both the mean activity and the absorbed-dose rate in regions of interest changed from positive to negative after 24 h after injection. Antigen-negative areas also increased over time in animals injected with unlabeled BR96, compared with untreated tumors. The results indicate that viable Lewis Y-expressing tumor cells are most efficiently treated during the initial uptake period. The activity then seems

  1. Sensitization of Primary Afferent Nociceptors Induced by Intradermal Capsaicin Involves the Peripheral Release of Calcitonin Gene-Related Peptide Driven by Dorsal Root Reflexes

    PubMed Central

    Li, Dingge; Ren, Yong; Xu, Xijin; Zou, Xiaoju; Fang, Li; Lin, Qing

    2008-01-01

    Neuropeptides released from axons of primary afferent nociceptive neurons are the key elements for the incidence of neurogenic inflammation and their release is associated with dorsal root reflexes (DRRs). However, whether the release is due to the triggering of DRRs and plays a role in inflammation-induced pain still remain to be determined. The present study assessed the role of calcitonin gene-related peptide (CGRP) in sensitization of primary afferent nociceptors induced by activation of transient receptor potential vanilloid-1 (TRPV1) following intradermal injection of capsaicin and determined if this release is due to activation of primary afferent neurons antidromically by triggering of DRRs. Under dorsal root intact conditions, primary afferent nociceptive fibers recorded in anesthetized rats could be sensitized by capsaicin injection, as shown by an increase in afferent responses and lowering of the response threshold to mechanical stimuli. After DRRs were removed by dorsal rhizotomy, the capsaicin-evoked sensitization was significantly reduced. In dorsal root intact rats, peripheral pretreatment with a CGRP receptor antagonist could dose-dependently reduce the capsaicin-induced sensitization. Peripheral post-treatment with CGRP could dose-dependently restore the capsaicin-induced sensitization under dorsal rhizotomized conditions. Capsaicin injection evoked increases in numbers of single and double labeled TRPV1 and CGRP neurons in ipsilateral dorsal root ganglia (DRG). After dorsal rhizotomy, these evoked expressions were significantly inhibited. Perspective These data indicate that the DRR-mediated neurogenic inflammation enhances sensitization of primary afferent nociceptors induced by capsaicin injection. The underlying mechanism involves antidromic activation of DRG neurons via up-regulation of TRPV1 receptors whereby CGRP is released peripherally. PMID:18701354

  2. Etanercept Injection

    MedlinePlus

    ... injection comes as a solution (liquid) in a prefilled syringe and an automatic injection device, and as a ... etanercept injection.If your medication comes in a prefilled syringe or automatic injection device, use each syringe or ...

  3. Broad and potent immune responses to a low dose intradermal HIV-1 DNA boosted with HIV-1 recombinant MVA among healthy adults in Tanzania☆,☆☆

    PubMed Central

    Bakari, Muhammad; Aboud, Said; Nilsson, Charlotta; Francis, Joel; Buma, Deus; Moshiro, Candida; Aris, Eric A.; Lyamuya, Eligius F.; Janabi, Mohamed; Godoy-Ramirez, Karina; Joachim, Agricola; Polonis, Victoria R.; Bråve, Andreas; Earl, Patricia; Robb, Merlin; Marovich, Mary; Wahren, Britta; Pallangyo, Kisali; Biberfeld, Gunnel; Mhalu, Fred; Sandström, Eric

    2016-01-01

    Background We conducted a phase I/II randomized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade, multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam, Tanzania. Methods Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1 mg intradermally (id), n = 20, or 3.8 mg intramuscularly (im), n = 20, or placebo, n = 20, using a needle-free injection device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B, C; rev B; p17/p24 gag A, B and Rtmut B were given at weeks 0, 4 and 12. Recombinant MVA (108 pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered im at month 9 and 21. Results The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-γ ELISpot responses to Gag. Two weeks after the first HIV-MVA boost all 35 (100%) vaccinees responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA boost, 28/29 (97%) vaccinees had IFN-γ ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env. The id-primed recipients had significantly higher responses to Env than im recipients. Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8+ and CD4+ T cell responses. All vaccinees had HIV-specific lymphoproliferative responses. All vaccinees reacted in diagnostic HIV serological tests and 26/29 (90%) had antibodies against gp160 after the second HIV-MVA boost. Furthermore, while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B, C and CRF01 AE pseudoviruses in the TZM-bl neutralization assay, in a PBMC assay, the response rate ranged from 31% to 83% positives, depending upon the clade B or CRF01_AE virus tested. This vaccine approach is safe and highly immunogenic. Low dose, id HIV-DNA priming elicited higher

  4. Susceptibility and resistance to Leishmania amazonensis in H-2q syngeneic high and low antibody responder mice (Biozzi mice).

    PubMed

    Lima, G M; Puel, A; Decreusefond, C; Bouthillier, Y; Mevel, J C; Abrahamsohn, I A; Mouton, D

    1998-08-01

    H-2 syngeneic H and L (Biozzi) mice provide a model to study Leishmania infections in which polar resistant and susceptible phenotypes are independent from H-2 differences. High-Ab-responder (H) and low-Ab-responder (L) mice syngeneic at the H-2 locus (H-2q) were, respectively, susceptible and highly resistant to Leishmania amazonensis infection. L-mice resistance was associated with high IFN-gamma and transient IL-4 production by lymph node (LN) cells, in contrast with sustained IL-4 and decreasing IFN-gamma production by susceptible H mice. IL-12 production could be detected only in LN from resistant mice. The cytokine production pattern was consistent with preferential progression to a Th1-type response in resistant L-mice, and to a Th2-type response in susceptible H-mice. We also investigated whether this shift towards Th1- or Th2-type cytokine responses was dependent upon H or L antigen presenting cells' (APC) intrinsic ability to preferentially stimulate either T-cell subset. To this end, LN-derived T-cell lines were grown from 12-day infected mice, when both strains produced IFN-gamma and IL-4. L-derived T-cell lines developed a Th2 cytokine pattern whereas H-derived T-cell lines produced IFN-gamma, IL-4 and IL-10 whatever the APC origin (H or L) used for their derivation. This work constitutes the first characterization of cellular immune responses to the intracellular parasite, L. amazonensis in H-2 syngeneic mice, an infection model in which polar resistant and susceptible phenotypes are determined by non-MHC genes.

  5. Intradermal DNA Electroporation Induces Cellular and Humoral Immune Response and Confers Protection against HER2/neu Tumor

    PubMed Central

    Lamolinara, Alessia; Stramucci, Lorenzo; Hysi, Albana; Iezzi, Manuela; Marchini, Cristina; Mariotti, Marianna; Amici, Augusto; Curcio, Claudia

    2015-01-01

    Skin represents an attractive target for DNA vaccine delivery because of its natural richness in APCs, whose targeting may potentiate the effect of vaccination. Nevertheless, intramuscular electroporation is the most common delivery method for ECTM vaccination. In this study we assessed whether intradermal administration could deliver the vaccine into different cell types and we analyzed the evolution of tissue infiltrate elicited by the vaccination protocol. Intradermal electroporation (EP) vaccination resulted in transfection of different skin layers, as well as mononuclear cells. Additionally, we observed a marked recruitment of reactive infiltrates mainly 6–24 hours after treatment and inflammatory cells included CD11c+. Moreover, we tested the efficacy of intradermal vaccination against Her2/neu antigen in cellular and humoral response induction and consequent protection from a Her2/neu tumor challenge in Her2/neu nontolerant and tolerant mice. A significant delay in transplantable tumor onset was observed in both BALB/c (p ≤ 0,0003) and BALB-neuT mice (p = 0,003). Moreover, BALB-neuT mice displayed slow tumor growth as compared to control group (p < 0,0016). In addition, while in vivo cytotoxic response was observed only in BALB/c mice, a significant antibody response was achieved in both mouse models. Our results identify intradermal EP vaccination as a promising method for delivering Her2/neu DNA vaccine. PMID:26247038

  6. Gua Sha, a press-stroke treatment of the skin, boosts the immune response to intradermal vaccination

    PubMed Central

    Liu, Jinxuan; Zhang, Xiaoying; Huang, Zhen; Zang, Yuhui; Chen, Jiangning; Dong, Lei

    2016-01-01

    Objective The skin is an important immunological barrier of the body as well as an optimal route for vaccine administration. Gua Sha, which involves press-stroke treatment of the skin, is an effective folk therapy, widely accepted in East Asia, for various symptoms; however, the mechanisms underlying its therapeutic effects have not been clarified. We investigated the influence of Gua Sha on the immunological features of the skin. Methods Gua Sha was performed on BALB/c mice and the effects were evaluated using anatomical, histological, and cytometric methods as well as cytokine determination locally and systemically. The effect on intradermal vaccination was assessed with antigen-specific subtype antibody responses. Results Blood vessel expansion, erythrocyte extravasation, and increased ratios of immune active cells were observed in the skin tissue following the treatment. Pro-inflammatory cytokines were up-regulated, and immunosuppressive cytokines, down-regulated, in the treated and untreated skin and systemic circulation; no obvious variations were detected in case of anti-inflammatory cytokines. Interestingly, intradermal delivery of a model vaccine following Gua Sha induced about three-fold higher IgG titers with a more Th1-biased antibody subtype profile. Conclusion Gua Sha treatment can up-regulate the innate and adaptive immune functions of the skin and boost the response against intradermal antigens. Thus, Gua Sha may serve as a safe, inexpensive, and independent physical adjuvant for intradermal vaccination. PMID:27672506

  7. Thermal hyperalgesia and light touch allodynia after intradermal Mycobacterium butyricum administration in rat.

    PubMed

    Arévalo, Maria Isabel; Escribano, Elvira; Calpena, Ana; Domenech, Josep; Queralt, Josep

    2003-10-01

    We examined the time course (7 weeks) of thermal hyperalgesia and light touch allodynia in rats after intradermal administration of Mycobacterium butyricum. Nociceptive thresholds to heat and light touch were assessed. Paw edema and temperature, motor function, body weight, and propioception were also tested. Some rats developed arthritis (named AA rats) but others did not (named non-AA rats). Both groups were compared with healthy animals. Persistent hyperalgesia was found in both groups; in AA rats it appeared before clinical evidence of arthritis. Transient allodynia ocurred only after edema development and fell when edema decreased. Motor function was impaired only in AA rats. The results of this study demonstrate that hyperalgesia, but not allodynia, appeared after Mycobacterium butyricum in both groups, suggesting that changes in sensitivity were not merely the result of local hypersensitivity of the inflamed tissue, but may also be due to alterations in nociception in the central nervous system.

  8. Intraoperative anaphylaxis to sugammadex and a protocol for intradermal skin testing.

    PubMed

    Sadleir, P H M; Russell, T; Clarke, R C; Maycock, E; Platt, P R

    2014-01-01

    Sugammadex is a selective binding agent for aminosteroid neuromuscular blockers whose use is increasing in anaesthetic practice. We present three cases of severe anaphylaxis coincident with sugammadex administration. Subsequent intradermal testing confirmed sugammadex as the triggering agent, with all patients having positive skin responses to a 1:100 dilution of the standard 100 mg/ml solution and two out of three having a positive response to a 1:1000 dilution. As all patients were administered sugammadex to reverse neuromuscular blockade with rocuronium, we considered that sugammadex-rocuronium complexes were a potential unique allergen. In the two patients who were additionally tested with a rocuronium-sugammadex (3.6:1 molecular ratio) mixture, the wheal-and-flare response was significantly attenuated.

  9. Intradermal immunization improves protective efficacy of a novel TB vaccine candidate.

    PubMed

    Baldwin, Susan L; Bertholet, Sylvie; Kahn, Maria; Zharkikh, Irina; Ireton, Gregory C; Vedvick, Thomas S; Reed, Steven G; Coler, Rhea N

    2009-05-18

    We have developed the Mycobacterium tuberculosis (Mtb) fusion protein (ID83), which contains the three Mtb proteins Rv1813, Rv3620 and Rv2608. We evaluated the immunogenicity and protective efficacy of ID83 in combination with several emulsion-formulated toll-like receptor agonists. The ID83 subunit vaccines containing synthetic TLR4 or TLR9 agonists generated a T helper-1 immune response and protected mice against challenge with Mtb regardless of route. The ID83 vaccine formulated with gardiquimod (a TLR7 agonist) also resulted in a protective response when administered intradermally, whereas the same vaccine given subcutaneously failed to provide protection. This highlights the need to explore different routes of immunization based on the adjuvant formulations used.

  10. Color-coded Imaging Enables Fluorescence-guided Surgery to Resect the Tumor Along with the Tumor Microenvironment in a Syngeneic Mouse Model of EL-4 Lymphoma.

    PubMed

    Hasegawa, Kosuke; Suetsugu, Atsushi; Nakamura, Miki; Matsumoto, Takuro; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Bouvet, Michael; Hoffman, Robert M

    2016-09-01

    Fluorescence-guided surgery (FGS) of cancer is an emerging technology. We have previously shown the importance of resecting both the tumor and the tumor microenvironment (TME) for curative FGS. We also previously developed a syngeneic model using the mouse lymphoma cell line EL-4, expressing red fluorescent protein (EL-4-RFP), growing in green fluorescent protein (GFP) transgenic mice, which we have used in the present report to develop FGS of the tumor microenvironment. EL-4-RFP lymphoma cells were injected subcutaneously in C57/BL6 GFP transgenic mice. EL-4-RFP cells subsequently formed tumors by 35 days after cell transplantation. Using the portable hand-held Dino-Lite digital imaging system, subcutaneous tumors were resected by FGS. Resected tumor tissues were visualized with the Olympus FV1000 confocal microscope. Using the Dino-Lite, subcutaneous tumors and the tumor microenvironment were clearly visualized and resected. In the resected tumor, host stromal cells, including adipocyte-like cells and blood vessels with lymphocytes, were observed by confocal microscopy in addition to cancer cells by color-coded confocal imaging. The cancer cells and stromal cells in the TME were deeply intermingled in a highly-complex pattern. Color-coded FGS is an effective method to completely resect cancer cells along with the stromal cells in the TME which interact in a highly-complex pattern. Microscopically, cancer cells invade the TME and vice versa. To prevent tumor recurrence, it is necessary to resect the TME along with the tumor. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Evaluation of locomotor function and microscopic structure of the spinal cord in a mouse model of experimental autoimmune encephalomyelitis following treatment with syngeneic mesenchymal stem cells

    PubMed Central

    Mitra, Nilesh Kumar; Bindal, Umesh; Eng Hwa, Wong; Chua, Caroline LL; Tan, Chek Ying

    2015-01-01

    Out of the minor myelin proteins, most significant one is myelin oligodendrocyte glycoprotein (MOG). Mesenchymal stem cells (MSCs) have proven immunoregulatory capacity. The objective of this study was to investigate the effects of syngeneic MSCs on mouse model of experimental autoimmune encephalomyelitis (EAE) through observation of locomotion by footprint analysis, histological analysis of spinal cord and estimation IL-17. C57BL/6 mice (10 weeks, n = 16) were immunized with 300 µg of MOG35-55 and 200 µL of complete Freund’s adjuvant (CFA) to produce EAE model. Sham-treated control (n = 8) were injected with CFA. Half of immunized mice were given 100 µL of PBS (n = 8) and next half (n = 8) received 1 × 105 MSCs on day 11 through the tail veins. Clinical scoring showed development of EAE (loss of tonicity of tail and weakness of hind limb) on day 10. Following MSC treatment, clinical scores and hindlimb stride length showed significant improvement on day 15 onwards, compared to day 10 (P < 0.05). Under LFB staining, while PBS-treated group of EAE mice showed pale and degenerated axons in anterolateral white column of lumbar spinal cord, MSC-treated group showed numerous normal-looking axons. H&E staining showed normal axons in anterolateral white column and reduction of macrophages in MSC-treated EAE mice group. A lower level of IL-17 was observed in MSC treated EAE mice, compared to PBS-treated EAE mice. Our results suggest that Intravenous MSC has the potential to improve the locomotion and regeneration of axons in spinal cord in MOG-induced EAE model. PMID:26722389

  12. The role of intradermal proliferation of T-cells in the pathogenesis of psoriasis*

    PubMed Central

    Khairutdinov, Vladislav R.; Mikhailichenko, Anastasiya F.; Belousova, Irena E.; Kuligina, Ekatherina Sh.; Samtsov, Alexey V.; Imyanitov, Evgeny N.

    2017-01-01

    BACKGROUND Psoriasis is a common immune-mediated chronic inflammatory disease of the skin and joints, affecting 1-3% of the population. It is generally accepted that the pathogenesis of psoriasis involves accumulation of effector T-cells within lymph nodes and their subsequent migration into the skin through the blood system. Here we provide evidence that psoriatic plaque itself may serve as a source of inflammatory T-cells. OBJECTIVE We examined the intradermal proliferation of T-cells and the number of effector/memory (CD45RO+) T-cells in the skin of psoriatic patients at different periods of the disease. METHODS Skin samples were obtained from 41 patients with progressive psoriatic lesions; 18 of these patients also donated skin specimens during the remission of the disease. The control group consisted of 16 healthy subjects. Ki-67 immunohistochemical staining was applied to detect proliferating cells, CD3ε served as a T-cell marker, and CD45RA and CD45RO antibodies were utilized to discriminate between naive and effector/memory T-cells, respectively. RESULTS Progressive psoriatic lesions demonstrated Ki67 staining both in keratinocytes and in the CD3ε+ cells of dermal infiltrate. Median count of CD45RO+ cells per microscopic field was 15 in healthy controls, 59 in patients in remission and 208 in progressive psoriatic plaques. The observed differences demonstrated high level of statistical significance. STUDY LIMITATIONS Limited number of analyzed patients. CONCLUSION Progressive phase of psoriasis is characterized by intradermal proliferation of T-cells. Spots of regressed psoriatic lesions contain high number of CD45RO+ cells, which are likely to render an immunological memory. PMID:28225955

  13. Control of postoperative pain after awake craniotomy with local intradermal analgesia and metamizol.

    PubMed

    Grossman, Rachel; Ram, Zvi; Perel, Azriel; Yusim, Yakov; Zaslansky, Ruth; Berkenstadt, Haim

    2007-05-01

    Pain following brain surgery is a significant problem. Infiltration of the scalp with local intradermal anesthetics was suggested for postoperative pain control but was assessed only in the first hour postoperatively. To evaluate wound infiltration with a single dose of metamizol (dipyrone) for postoperative pain control in patients undergoing awake craniotomy. This open, prospective, non-randomized observational study, conducted in anesthesiology and neurosurgical departments of a teaching hospital, included 40 patients undergoing awake craniotomy for the removal of brain tumor. Intraoperative anesthesia included wound infiltration with lidocaine and bupivacaine, conscious sedation using remifentanil and propofol, and a single dose of metamizol (dipyrone) for postoperative pain control. Outcome was assessed by the Numerical Pain Scale on arrival at the postoperative care unit, and 2, 4 and 12 hours after the end of surgery. On arrival at the postoperative care unit, patients reported NPS scores of 1.2 +/- 1.1 in a scale of 0-10 (mean +/- SD) (median = 1, range 0-4). The scores were 0.8 +/-0.9, 0.9 +/- 0.9 and 1 +/- 0.9 at 2 hours, 4 hours and 12 hours after the end of surgery, respectively. Based on patients' complaints and NPS lower than 3, 27 patients did not require any supplementary analgesia during the first 12 postoperative hours, 11 patients required a single dose of oral metamizol or intramuscular diclofenac, one patient was given 2 mg of intravenous morphine, and one patient required two separate doses of metamizol. Although the clinical setup prevents the use of placebo local analgesia as a control group, the results suggest the possible role of local intradermal infiltration of the scalp combined with a single dose of metamizol to control postoperative pain in patients undergoing craniotomy.

  14. Evaluation of cross-reactivity of allergens by use of intradermal testing in atopic dogs.

    PubMed

    Mueller, Ralf S; Chapman, Phillip L; Rosychuk, Rodney E W; Bettenay, Sonya V; Fieseler, Kathryn V

    2002-06-01

    To examine cross-reactivity of aeroallergens in Colorado and surrounding states by evaluating concurrent positive reactions of related and nonrelated allergens of intradermal tests in dogs. Intradermal test results of 268 atopic dogs. A retrospective evaluation of skin test results for 268 dogs was performed. Pairs of closely related and nonrelated allergens were evaluated. Group 1 consisted of closely related allergens with demonstrated antibody cross-reactivity in humans. In group 2, allergens of the same plant group (ie, trees, grasses, or weeds) that were not closely related were paired. In group 3, allergen pairs were of different plant groups. Plant allergens were paired with dust mite allergens, animal dander, or mold spores in group 4. In the last group, allergens not derived from plants were paired. Data were evaluated twice by use of a different definition of a positive reaction. Significance of the difference between group means of log odds ratios was estimated by use of a boot-strap percentile confidence interval. Significant differences in the number of concurrent positive reactions were not found between related versus nonrelated grass, weed, or tree allergens. Significant differences in the number of concurrent positive reactions were found between plant allergens of different groups (ie, grasses, weeds, and trees) and plant allergens of the same groups, related or nonrelated, as well as between plant-derived and nonplant-derived allergens. Many dogs reacting to a specific allergen did not react to a closely related allergen at the same time. These results provide evidence against clinically relevant cross-reactivity and suggest that allergen-specific immunotherapy should be formulated on the basis of single allergen test results.

  15. [Permanent tattoos following injections with Dermo-Jet: anatomoclinical study. Apropos of 5 cases].

    PubMed

    Lachapelle, J M; Tennstedt, D; Burtonboy, G

    1982-01-01

    Blue or black tattoos were observed in five patients who had received several intradermal injections (of a lidocaine solution or of a triamcinolone acetonide suspension) with the Dermo-Jet. A histological examination revealed the presence of black masses, rounded or elongated, different in size, distributed throughout dermal tissue. Additionally, conglomerates of black grains in the cytoplasm of histiocytes and of pericytes are precisely observed in semi-thin sections. It has been proved by several investigations that these foreign particles are not of metallic nature. It can be concluded from electron microscopic studies that the particles are fragments of black rubber, from the upper joint of the reservoir. Indeed, some rubber fragments are leached into the reservoir. Some of these are passing through the wire-mesh filter of the nozzle (with the solution or the suspension) when injections are made. Therefore, they are injected intradermally and are permanently tattooing the skin.

  16. MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice.

    PubMed

    Hirata, Yuichi; Li, Hao-Wei; Takahashi, Kazuko; Ishii, Hiroshi; Sykes, Megan; Fujisaki, Joji

    2015-01-01

    NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives. However, using high-resolution in vivo imaging, we demonstrated here that syngeneic MHC class I knockout (KO) donor HSPCs persist with the same survival frequencies as wild-type donor HSPCs. In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion. In vivo time-lapse imaging demonstrated that mice receiving allogeneic MHC class I KO HSPCs showed a significant increase in NK cell motility and proliferation as well as frequencies of NK cell contact with and killing of HSPCs as compared to mice receiving wild-type HSPCs. The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs.

  17. MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice

    PubMed Central

    Hirata, Yuichi; Li, Hao-Wei; Takahashi, Kazuko; Ishii, Hiroshi; Sykes, Megan; Fujisaki, Joji

    2015-01-01

    NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives. However, using high-resolution in vivo imaging, we demonstrated here that syngeneic MHC class I knockout (KO) donor HSPCs persist with the same survival frequencies as wild-type donor HSPCs. In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion. In vivo time-lapse imaging demonstrated that mice receiving allogeneic MHC class I KO HSPCs showed a significant increase in NK cell motility and proliferation as well as frequencies of NK cell contact with and killing of HSPCs as compared to mice receiving wild-type HSPCs. The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs. PMID:26544200

  18. Intradermal vaccination with un-adjuvanted sub-unit vaccines triggers skin innate immunity and confers protective respiratory immunity in domestic swine.

    PubMed

    Le Luduec, Jean-Benoît; Debeer, Sabine; Piras, Fabienne; Andréoni, Christine; Boudet, Florence; Laurent, Philippe; Kaiserlian, Dominique; Dubois, Bertrand

    2016-02-10

    Intradermal (ID) vaccination constitutes a promising approach to induce anti-infectious immunity. This route of immunization has mostly been studied with influenza split-virion vaccines. However, the efficacy of ID vaccination for sub-unit vaccines in relation to underlying skin innate immunity remains to be explored for wider application in humans. Relevant animal models that more closely mimic human skin immunity than the widely used mouse models are therefore necessary. Here, we show in domestic swine, which shares striking anatomic and functional properties with human skin, that a single ID delivery of pseudorabies virus (PRV) glycoproteins without added adjuvant is sufficient to trigger adaptive cellular and humoral immune responses, and to confer protection from a lethal respiratory infection with PRV. Analysis of early events at the skin injection site revealed up-regulation of pro-inflammatory cytokine and chemokine genes, recruitment of neutrophils and monocytes and accumulation of inflammatory DC. We further show that the sustained induction of pro-inflammatory cytokine genes results from the combined effects of skin puncture, liquid injection in the dermis and viral antigens. These data highlight that immune protection against respiratory infection can be induced by ID vaccination with a subunit vaccine and reveal that adjuvant requirements are circumvented by the mechanical and antigenic stress caused by ID injection, which triggers innate immunity and mobilization of inflammatory DC at the immunization site. ID vaccination with sub-unit vaccines may thus represent a safe and efficient solution for protection against respiratory infections in swine and possibly also in humans, given the similarity of skin structure and function in both species.

  19. Mixed lymphocyte reactivity against normal cells by splenic lymphocytes from tumor-bearing mice : ii. Studies of autoimmune-like activity in completely syngeneic and semisyngeneic systems.

    PubMed

    Devlin, R G; McCurdy, J D; Baronowsky, P E

    1974-01-01

    A possible consequence of an antilymphocytic autoimmune process would be serious impairment of an animal's ability to destroy tumor cells. One measure of autoimmune reactivity of this type would be the demonstration of cellular immune responsiveness by cells from tumor-bearing mice against syngeneic normal cells. These experiments demonstrate that spleen cells from mice bearing a lymphocytic leukemia of identical histocompatability type as the host mounted a vigorous immune response against normal syngeneic cells in a mixed lymphocyte reaction (MLR). Moreover, ascitic cells from leukemic mice responded significantly to normal syngeneic spleen cells in MLR's. The former reactions are usually much more vigorous than the responses of normal to malignant cells. These results are discussed in terms of the relationship between autoimmunity and neoplasia. Alternative explanations necessitated by the dangers involved in the interpretation of the immunology of transplantable tumors are considered.

  20. Pegfilgrastim Injection

    MedlinePlus

    Pegfilgrastim comes as a solution (liquid) in prefilled injection syringes and in a pre-filled automatic injection device (On-body Injector) to inject subcutaneously (under the skin). If you are using pegfilgrastim to ...

  1. Cabazitaxel Injection

    MedlinePlus

    ... injection is used along with prednisone to treat prostate cancer (cancer of a male reproductive organ) that has ... cabazitaxel injection is usually used in men with prostate cancer. If used by pregnant women, cabazitaxel injection can ...

  2. Ondansetron Injection

    MedlinePlus

    Zofran® Injection ... Ondansetron injection is used to prevent nausea and vomiting caused by cancer chemotherapy and surgery. Ondansetron is in a ... medications: or any of the ingredients in ondansetron injection. Ask your pharmacist for a list of the ...

  3. Usefulness of confocal microscopy in distinguishing between basal cell carcinoma and intradermal melanocytic nevus on the face.

    PubMed

    Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L

    2015-10-01

    The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma.

  4. Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients.

    PubMed

    Rittig, Susanne M; Haentschel, Maik; Weimer, Katrin J; Heine, Annkristin; Muller, Martin R; Brugger, Wolfram; Horger, Marius S; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans-Georg; Holderried, Tobias A W; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

    2011-05-01

    The aim of this phase I/II nonrandomized trial was to assess feasibility, safety as well as immunological and clinical responses of a mRNA-based vaccination in patients with stage IV renal cell cancer using granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvant. Intradermal injections of in vitro transcribed naked mRNA, which was generated using plasmids coding for the tumor-associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated antigen 1 (MAGE-A1) were performed in 30 enrolled patients. In the first 14 patients (cohort A) vaccinations were administered on days 0, 14, 28, and 42 (20 µg/antigen) while in the consecutive 16 patients (cohort B) an intensified protocol consisting of injections at days 0-3, 7-10, 28, and 42 (50 µg/antigen) was used. In both cohorts, after this induction period, vaccinations were repeated monthly until tumor progression analyzed by Response Evaluation Criteria In Solid Tumors criteria (RECIST). Vaccinations were well tolerated with no severe side effects and induced clinical responses [six stable diseases (SD) and one partial response in cohort A and nine SD in cohort B]. In cohort A, 35.7% survived 4 years (median survival 24 months) compared to 31.25% in cohort B (median survival 29 months). Induction of CD4(+) and CD8(+) T cell responses was shown for several tumor-associated antigens (TAA) using interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.

  5. Ibandronate Injection

    MedlinePlus

    Boniva® Injection ... Ibandronate injection is used to treat osteoporosis (a condition in which the bones become thin and weak and break ... Ibandronate injection comes as a solution (liquid) to be injected into a vein by a doctor or nurse in ...

  6. Leuprolide Injection

    MedlinePlus

    Leuprolide injection comes as a long-acting suspension (Lupron) that is injected intramuscularly (into a muscle) by a doctor or nurse in a medical ... Depot-4 month, Lupron Depot-6 Month). Leuprolide injection also comes as a long-acting suspension (Eligard) that is injected subcutaneously (just under ...

  7. [Reactogenicity and immunogenicity of intradermal flu vaccine among the medical students of the University of Rome Tor Vergata].

    PubMed

    Morciano, Laura; Zaratti, Laura; Carlino, Cristiana; Visconti, Giuseppe; Magrini, Andrea; Franco, Elisabetta

    2012-01-01

    Healthcare workers and medical students are a preferencial category for the administration of the seasonal influenza vaccination both for the protection of the patient and the continuity of care. Despite this the coverage remains low throughout the world. The purpose of this study was to evaluate the acceptability of the influenza vaccination among the students of the school of Medicine and Health Professions. The reactogenicity and the perception of protection offered by the administration of the intradermal influenza vaccine were specifically evaluated.

  8. [Proliferation of beta cells after syngeneic transplantation of isolated Langerhans cells into the spleens of diabetic rats].

    PubMed

    Wohlrab, F; Schmidt, S; Kloeting, I; Wilke, B; Cossel, L

    1990-01-01

    Syngeneic transplantation of cultured and functionally characterized neonatal islet into the spleen of streptozotocin diabetic Lewis rats resulted in long time survival up to 200 days and in plasma glucose levels lower than 9 mmol/l. The daily plasma glucose profile of transplanted rats had shown significantly above that of non diabetic control rats. 200 days after transplantation morphologically intact, insulin containing beta-cells were demonstrable in the spleen, thus demonstrating the long-term survival of functioning islet cells. Proliferation of beta-cells was shown in the transplanted islets. In addition, beta-cell clusters were found which derived from pancreatic ductules transplanted together with the isolated islets into the spleen. Mitose were visible within ductular epithelial cells. The proliferative response of islets after intrasplenic transplantation is probably the result of a long-term stimulation by slightly enhanced plasma glucose values of the transplanted acceptors compared to control animals.

  9. Leukemia in AKR mice. I. Effects of leukemic cells on antibody-forming potential of syngeneic and allogeneic normal cells

    PubMed Central

    1976-01-01

    Cells from the spleen, thymus, lymph node, and liver of leukemic AKR mice suppress in vitro antibody responses of normal syngeneic and semiallogeneic cells. This suppression can be mediated by irradiated leukemic cells, requires cell contact between leukemic and normal cells, and may occur at any time during the in vitro culture period. Leukemic AKR cells do not suppress antibody responses of allogeneic cells, even when allogeneic cells have H-2 or background genes homologous with AKR. Leukemic cells do, however, suppress cells that are unable to respond allogeneically to leukemic AKR cells, such as cells of the F1s of AKR. Suppression of normal AKR antibody responses by leukemic AKR cells may be overcome by addition of irradiated allogeneic cells. The fact that leukemic AKR cells are able to suppress normal lymphocyte responses may be of significance in pathogenesis of leukemia in these mice. PMID:942993

  10. Rabies intradermal post-exposure vaccination of humans using reconstituted and stored vaccine.

    PubMed

    Kamoltham, Thavachai; Khawplod, Pakamatz; Wilde, Henry

    2002-09-10

    Thailand's northern Petchabun province is endemic for canine rabies. There were 27 reported human rabies deaths between 1989 and 1998. A rabies control plan was formulated in 1997 between medical and veterinary public health officials. It started an intense education program and an ongoing dog vaccination campaign. Economic constraints and the high cost of biological were the main reasons for inadequate human post-exposure management (PET). It was therefore decided to use the economical Thai Red Cross Intradermal Vaccine Regimen (TRC-ID) throughout the province. The original TRC-ID method is only suitable for clinics that see more than one PET patient daily. TRC-ID was therefore modified by storing the reconstituted vaccine in a refrigerator for the same patient's next two visits. Data on a total of 8157 PET patients were collected. An additional modification of TRC-ID also eliminated the 90 day booster. There were no treatment failures and no human rabies deaths in 1999, 2000 and 2001. The modified TRC-ID method induces adequate levels of neutralizing antibodies, protects humans bitten by rabid dogs and results in significant savings in vaccine and travel costs.

  11. Evaluation of Erysipelothrix rhusiopathiae vaccines in pigs by intradermal challenge and immune responses.

    PubMed

    Eamens, G J; Chin, J C; Turner, B; Barchia, I

    2006-08-25

    In a vaccine trial, pigs were challenged intradermally with eight E. rhusiopathiae strains of serovars 1a, 1b or 2 given concurrently. The strains were derived from six herds affected with vaccine breakdowns in 1997-1999, one herd without vaccine breakdown and a serovar 2 reference strain. Responses to two commercial bacterins (one implicated in the vaccine breakdowns), and two experimental bacterins (based on field isolates from affected herds) showed distinct differences in protection, particularly in clinical responses measured at 72 h. Less protection was afforded against serovar 1 challenge by the vaccine implicated in the vaccine breakdowns. Antibody and cell-mediated immune (CMI) responses were significantly different between treatments, and highlighted a similar post-vaccinal antibody response was produced against serovar 2 lysate by all vaccines, but only those providing significant protection against serovar 1 [corrected] produced significantly elevated antiserovar I lysate [corrected] antibodies. Vaccination in general significantly reduced CMI responses to the mitogens concanavalin A and phytohaemagglutinin. This experimental pig challenge system was readily able to confirm suboptimal performance of a commercial bacterin that had passed potency tests in mice but was associated with vaccine failure in commercial herds. This vaccine was also the most immunosuppressive to CMI responses associated with E. rhusiopathiae-specific and non-specific stimulation. The best vaccine response was associated with the highest mean serovar 1 antibody response and the highest CMI response (by lymphoproliferation assay) to serovar 2.

  12. Hollow agarose microneedle with silver coating for intradermal surface-enhanced Raman measurements: a skin-mimicking phantom study

    NASA Astrophysics Data System (ADS)

    Yuen, Clement; Liu, Quan

    2015-06-01

    Human intradermal components contain important clinical information beneficial to the field of immunology and disease diagnosis. Although microneedles have shown great potential to act as probes to break the human skin barrier for the minimally invasive measurement of intradermal components, metal microneedles that include stainless steel could cause the following problems: (1) sharp waste production, and (2) contamination due to reuse of microneedles especially in developing regions. In this study, we fabricate agarose microneedles coated with a layer of silver (Ag) and demonstrate their use as a probe for the realization of intradermal surface-enhanced Raman scattering measurements in a set of skin-mimicking phantoms. The Ag-coated agarose microneedle quantifies a range of glucose concentrations from 5 to 150 mM inside the skin phantoms with a root-mean-square error of 5.1 mM within 10 s. The needle is found enlarged by 53.9% after another 6 min inside the phantom. The shape-changing capability of this agarose microneedle ensures that the reuse of these microneedles is impossible, thus avoiding sharp waste production and preventing needle contamination, which shows the great potential for safe and effective needle-based measurements.

  13. Insight into the immunobiology of human skin and functional specialization of skin dendritic cell subsets to innovate intradermal vaccination design.

    PubMed

    Teunissen, M B M; Haniffa, M; Collin, M P

    2012-01-01

    Dendritic cells (DC) are the key initiators and regulators of any immune response which determine the outcome of CD4(+) and CD8(+) T-cell responses. Multiple distinct DC subsets can be distinguished by location, phenotype, and function in the homeostatic and inflamed human skin. The function of steady-state cutaneous DCs or recruited inflammatory DCs is influenced by the surrounding cellular and extracellular skin microenvironment. The skin is an attractive site for vaccination given the extended local network of DCs and the easy access to the skin-draining lymph nodes to generate effector T cells and immunoglobulin-producing B cells for long-term protective immunity. In the context of intradermal vaccination we describe in this review the skin-associated immune system, the characteristics of the different skin DC subsets, the mechanism of antigen uptake and presentation, and how the properties of DCs can be manipulated. This knowledge is critical for the development of intradermal vaccine strategies and supports the concept of intradermal vaccination as a superior route to the conventional intramuscular or subcutaneous methods.

  14. Hollow agarose microneedle with silver coating for intradermal surface-enhanced Raman measurements: a skin-mimicking phantom study.

    PubMed

    Yuen, Clement; Liu, Quan

    2015-06-01

    Human intradermal components contain important clinical information beneficial to the field of immunology and disease diagnosis. Although microneedles have shown great potential to act as probes to break the human skin barrier for the minimally invasive measurement of intradermal components, metal microneedles that include stainless steel could cause the following problems: (1) sharp waste production, and (2) contamination due to reuse of microneedles especially in developing regions. In this study, we fabricate agarose microneedles coated with a layer of silver (Ag) and demonstrate their use as a probe for the realization of intradermal surface enhanced Raman scattering measurements in a set of skin-mimicking phantoms. The Ag-coated agarose microneedle quantifies a range of glucose concentrations from 5 to 150 mM inside the skin phantoms with a root-mean-square error of 5.1 mM within 10 s. The needle is found enlarged by 53.9% after another 6 min inside the phantom. The shape-changing capability of this agarose microneedle ensures that there use of these microneedles is impossible, thus avoiding sharp waste production and preventing needle contamination,which shows the great potential for safe and effective needle-based measurements.

  15. Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease

    PubMed Central

    Brandon, J. Anthony; Perez, Jacqueline; Jennings, C. Darrell; Cohen, Donald A.; Sindhava, V. J.; Bondada, S.; Kaplan, Alan M.

    2010-01-01

    The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4+ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals that developed colitis also develop chronic liver inflammation. Liver samples from control and SGVHD animals were monitored for tissue pathology, RNA for inflammatory mediators, and phenotypic analysis and in vitro reactivity of the inflammatory infiltrate. Diseased animals developed lesions of intrahepatic and extrahepatic bile ducts. Elevated levels of mRNA for molecules associated with chronic liver inflammation, including mucosal cellular adhesion molecule −1, the chemokines CCL25, CCL28, CCR9, and TH1- and TH17-associated cytokines were observed in livers of SGVHD mice. CD4+ T cells were localized to the peribiliary region of the livers of diseased animals, and an enhanced proliferative response of liver-associated mononuclear cells against colonic bacterial antigens was observed. The murine model of SGVHD colitis may be a valuable tool to study the entero-hepatic linkage between chronic colon inflammation and inflammatory liver disease. PMID:20634434

  16. Y chromosome detection of three-dimensional tissue-engineered skeletal muscle constructs in a syngeneic rat animal model.

    PubMed

    Beier, J P; Kneser, U; Stern-Sträter, J; Stark, G B; Bach, A D

    2004-01-01

    Surgical reconstruction of muscle tissue lost by trauma or tumor ablation is limited by the lack of availability of functional native tissue substitution. Moreover, so far most inherited or acquired muscle diseases are lacking sufficient treatment, because only few alternatives exist to provide functional restoration of lost muscle tissues. Engineering those tissues and transplantation into sites of dysfunction may be an alternative approach and may allow replacement of such damaged or failing skeletal muscle tissues. Techniques attempting reconstruction of some human tissues and organs (tissue engineering) have been introduced into clinical practice recently. One major problem that previous transplantation studies were facing is the ability of detection of transplanted cells after integration. Using the Y chromosome in situ hybridization technique in a syngeneic rat model allows transplantation of cell constructs orthotopically, without manipulation of the cells, with no rejection or immunosuppression being implied, but providing a nondilutable genetic marker to identify transplanted cells. The purpose of our study was to create functional skeletal muscle tissue in vivo using the transplantation of primary myoblasts precultivated within a three-dimensional (3D) fibrin matrix and to determine the fate of the transplanted cells using the Y chromosome detection technique. 3D myoblast cultures were established derived from male donor rats and after 7 days of cultivation we performed an orthotopic transplantation of 3D cell constructs into a created muscle defect within the gracilis muscle of syngeneic female rats. Anti-desmin immunostaining and Y chromosome in situ hybridization indicated the survival and integration of transplanted male myoblasts into the female recipient animal, thus demonstrating the feasibility of this approach in tissue engineering and the research of cell transplantation in general.

  17. Color-Coded Imaging of Syngeneic Orthotopic Malignant Lymphoma Interacting with Host Stromal Cells During Metastasis.

    PubMed

    Matsumoto, Takuro; Suetsugu, Atsushi; Hasegawa, Kosuke; Nakamura, Miki; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

    2016-04-01

    The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. In a previous study, EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were established and injected into the tail vein of C57/BL6 green fluorescent protein (GFP) transgenic mice. Metastasis was observed at multiple sites which were also enriched with host GFP-expressing stromal cells. In the present study, our aim was to establish an orthotopic model of EL4-RFP. In the present study, EL4-RFP lymphoma cells were injected in the spleen of C57/BL6 GFP transgenic mice as an orthotopic model of lymphoma. Resultant primary tumor and metastases were imaged with the Olympus FV1000 scanning laser confocal microscope. EL4-RFP metastasis was observed 21 days later. EL4-RFP tumors in the spleen (primary injection site), liver, supra-mediastinum lymph nodes, abdominal lymph nodes, bone marrow, and lung were visualized by color-coded imaging. EL4-RFP metastases in the liver, lymph nodes, and bone marrow in C57/BL6 GFP mice were rich in GFP stromal cells such as macrophages, fibroblasts, dendritic cells, and normal lymphocytes derived from the host animal. Small tumors were observed in the spleen, which were rich in host stromal cells. In the lung, no mass formation of lymphoma cells occurred, but lymphoma cells circulated in lung peripheral blood vessels. Phagocytosis of EL4-RFP lymphoma cells by macrophages, as well as dendritic cells and fibroblasts, were observed in culture. Color-coded imaging of the lymphoma microenvironment suggests an important role of stromal cells in lymphoma progression and metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-10-01

    Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI.

  19. Golimumab Injection

    MedlinePlus

    ... body and causes pain, swelling, and damage) including: rheumatoid arthritis (condition in which the body attacks its own ... doctor.If golimumab injection is used to treat rheumatoid arthritis, it may also be injected intravenously (into a ...

  20. Adalimumab Injection

    MedlinePlus

    ... causes pain, swelling, and damage) including the following: rheumatoid arthritis (a condition in which the body attacks its ... If you are using adalimumab injection to treat rheumatoid arthritis, your doctor may tell you to inject the ...

  1. Ipilimumab Injection

    MedlinePlus

    ... are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while receiving ipilimumab injection, call your doctor. Ipilimumab injection may cause your baby to be born too early or to die before birth.

  2. Teniposide Injection

    MedlinePlus

    ... in men. You should not become pregnant or breast-feed while you are receiving teniposide injection. If you or your partner become pregnant while receiving teniposide injection, call your doctor. Teniposide may harm the fetus.

  3. Dexrazoxane Injection

    MedlinePlus

    ... Dexrazoxane injection (Zinecard) is used to prevent or decrease heart damage caused by doxorubicin in women who ... with doxorubicin. Dexrazoxane injection (Totect) is used to decrease damage to the skin and tissues that may ...

  4. Colistimethate Injection

    MedlinePlus

    ... is used to treat certain infections caused by bacteria. Colistimethate injection is in a class of medications called antibiotics. It works by killing bacteria.Antibiotics such as colistimethate injection will not work ...

  5. Chloramphenicol Injection

    MedlinePlus

    ... treat certain types of serious infections caused by bacteria when other antibiotics cannot be used. Chloramphenicol injection ... antibiotics. It works by stopping the growth of bacteria..Antibiotics such as chloramphenicol injection will not work ...

  6. Natalizumab Injection

    MedlinePlus

    ... your condition. Keep all appointments to receive natalizumab injection even if you feel well. ... tests to check your body's response to natalizumab injection.It is important ... you are taking, as well as any products such as vitamins, minerals, or ...

  7. Methylnaltrexone Injection

    MedlinePlus

    ... taking opioid medications, you should stop using methylnaltrexone injection as well.You should stop taking other laxative medications when you start using methylnaltrexone injection. However, be sure to let your doctor know ...

  8. Triptorelin Injection

    MedlinePlus

    ... used to treat the symptoms associated with advanced prostate cancer. Triptorelin injection (Triptodur) is used to treat central ... a medical office or clinic. When used for prostate cancer, an injection of 3.75 mg of triptorelin ( ...

  9. Degarelix Injection

    MedlinePlus

    Degarelix injection is used to treat advanced prostate cancer (cancer that begins in the prostate [a male reproductive gland]). Degarelix injection is in a class of medications called gonadotropin-releasing hormone (GnRH) ...

  10. Medroxyprogesterone Injection

    MedlinePlus

    ... Medroxyprogesterone injection is a very effective method of birth control but does not prevent the spread of human ... you have been using a different method of birth control and are switching to medroxyprogesterone injection, your doctor ...

  11. Dolasetron Injection

    MedlinePlus

    ... treat nausea and vomiting that may occur after surgery. Dolasetron injection should not be used to prevent ... a single injection just before the end of surgery or as soon as nausea or vomiting occurs. ...

  12. Levoleucovorin Injection

    MedlinePlus

    Levoleucovorin injection is used to prevent harmful effects of methotrexate (Rheumatrex, Trexall) when methotrexate is used to to treat certain types of cancer. Levoleucovorin injection is also used to treat people ...

  13. Etelcalcetide Injection

    MedlinePlus

    Etelcalcetide injection is used to treat secondary hyperparathyroidism (condition in which the body produces too much parathyroid ... blood when the kidneys are not working properly.) Etelcalcetide injection is in a class of medications called ...

  14. Dupilumab Injection

    MedlinePlus

    ... injection is used to treat the symptoms of eczema (atopic dermatitis; a skin disease that causes the ... use other medications for their condition or whose eczema has not responded to other medications. Dupilumab injection ...

  15. Methylprednisolone Injection

    MedlinePlus

    ... allergic reactions. Methylprednisolone injection is used in the management of multiple sclerosis (a disease in which the ... laboratory test, tell your doctor and the laboratory personnel that you are using methylprednisolone injection.If you ...

  16. Clindamycin Injection

    MedlinePlus

    ... your treatment with clindamycin injection or during the first several months after your treatment is finished: watery or bloody stools, diarrhea, stomach cramps, or fever.Talk to your doctor about the risks of receiving clindamycin injection.

  17. Obinutuzumab Injection

    MedlinePlus

    Obinutuzumab injection is used with chlorambucil (Leukeran) to treat chronic lymphocytic leukemia (CLL; a type of cancer of the white blood cells). Obinutuzumab injection is in a class of medications called ...

  18. Ferumoxytol Injection

    MedlinePlus

    Ferumoxytol injection is used to treat iron-deficiency anemia (a lower than normal number of red blood ... and may cause the kidneys to stop working). Ferumoxytol injection is in a class of medications called ...

  19. Pralatrexate Injection

    MedlinePlus

    Pralatrexate injection is used to treat peripheral T-cell lymphoma (PTCL; a form of cancer that begins in a ... come back after treatment with other medications. Pralatrexate injection has not been shown to help people who ...

  20. Cyanocobalamin Injection

    MedlinePlus

    Cyanocobalamin injection is used to treat and prevent a lack of vitamin B12 that may be caused by any ... organs) and permanent damage to the nerves. Cyanocobalamin injection also may be given as a test to ...

  1. Paclitaxel Injection

    MedlinePlus

    Paclitaxel injection manufactured with human albumin is used to treat breast cancer that has not improved or that has come back after treatment with other medications. Paclitaxel injection manufactured with polyoxyethylated castor oil is used to ...

  2. Peramivir Injection

    MedlinePlus

    Peramivir injection is used to treat some types of influenza infection ('flu') in people who have had symptoms of ... flu for no longer than 2 days. Peramivir injection is in a class of medications called neuraminidase ...

  3. Cefotetan Injection

    MedlinePlus

    Cefotetan injection is used to treat infections of the lungs, skin, bones, joints, stomach area, blood, female reproductive organs, and urinary tract. Cefotetan injection is also used before surgery to prevent infections. ...

  4. Mipomersen Injection

    MedlinePlus

    Mipomersen injection is used to decrease levels of cholesterol and other fatty substances in the blood in people who ... that removes LDL from the blood), but mipomersen injection should not be used along with this treatment. ...

  5. Romiplostim Injection

    MedlinePlus

    Romiplostim injection is used to increase the number of platelets (cells that help the blood to clot) in order ... low number of platelets in the blood). Romiplostim injection should only be used in people who cannot ...

  6. Hydrocortisone Injection

    MedlinePlus

    Hydrocortisone injection is used to treat symptoms of low corticosteroid levels (lack of certain substances that are usually produced ... also used to treat severe allergic reactions. Hydrocortisone injection is used in the management of multiple sclerosis ( ...

  7. Palivizumab Injection

    MedlinePlus

    Palivizumab injection is used to help prevent respiratory syncytial virus (RSV; common virus that can cause serious lung infections) ... or have certain heart or lung diseases. Palivizumab injection is not used to treat the symptoms of ...

  8. Naltrexone Injection

    MedlinePlus

    Naltrexone injection is used along with counseling and social support to help people who have stopped drinking large amounts of alcohol to avoid drinking again. Naltrexone injection is also used along with counseling and social ...

  9. Tesamorelin Injection

    MedlinePlus

    Tesamorelin injection is used to decrease the amount of extra fat in the stomach area in adults with human ... fat in certain areas of the body). Tesamorelin injection is not used to help with weight loss. ...

  10. Tigecycline Injection

    MedlinePlus

    Tigecycline injection used to treat certain serious infections including community acquired pneumonia (a lung infection that developed in a ... area between the chest and the waist). Tigecycline injection should not be used to treat pneumonia that ...

  11. Eculizumab Injection

    MedlinePlus

    Eculizumab injection is used to treat paroxysmal nocturnal hemoglobinuria (PNH: a type of anemia in which too many red ... oxygen to all parts of the body). Eculizumab injection is also used to treat atypical hemolytic uremic ...

  12. Pembrolizumab Injection

    MedlinePlus

    Pembrolizumab injection is used to treat melanoma (a type of skin cancer) that cannot be treated with surgery or ... spread to other parts of the body. Pembrolizumab injection is also used to treat a certain type ...

  13. Oxacillin Injection

    MedlinePlus

    ... is used to treat infections caused by certain bacteria. Oxacillin injection is in a class of medications called penicillins. It works by killing bacteria.Antibiotics such as oxacillin injection will not work ...

  14. Cefoxitin Injection

    MedlinePlus

    ... injection is used to treat infections caused by bacteria including pneumonia and other lower respiratory tract (lung) ... medications called cephamycin antibiotics. It works by killing bacteria.Antibiotics such as cefoxitin injection will not work ...

  15. Nafcillin Injection

    MedlinePlus

    ... to treat infections caused by certain types of bacteria. Nafcillin injection is in a class of medications called penicillins. It works by killing bacteria.Antibiotics such as nafcillin injection will not work ...

  16. Doripenem Injection

    MedlinePlus

    ... tract, kidney, and abdomen that are caused by bacteria. Doripenem injection is not approved by the Food ... medications called carbapenem antibiotics. It works by killing bacteria.Antibiotics such as doripenem injection will not work ...

  17. Intradermal tuberculin testing of wild African lions (Panthera leo) naturally exposed to infection with Mycobacterium bovis.

    PubMed

    Keet, D F; Michel, A L; Bengis, R G; Becker, P; van Dyk, D S; van Vuuren, M; Rutten, V P M G; Penzhorn, B L

    2010-08-26

    African lions in the southern half of Kruger National Park (KNP) are infected with Mycobacterium bovis. Historically, reliable detection of mycobacteriosis in lions was limited to necropsy and microbiological analysis of lesion material collected from emaciated and ailing or repeat-offender lions. We report on a method of cervical intradermal tuberculin testing of lions and its interpretation capable of identifying natural exposure to M. bovis. Infected lions (n=52/95) were identified by detailed necropsy and mycobacterial culture. A large proportion of these confirmed infected lions (45/52) showed distinct responses to bovine tuberculin purified protein derivative (PPD) while responses to avian tuberculin PPD were variable and smaller. Confirmed uninfected lions from non-infected areas (n=11) responded variably to avian tuberculin PPD only. Various non-tuberculous mycobacteria (NTM) were cultured from 45/95 lions examined, of which 21/45 were co-infected with M. bovis. Co-infection with M. bovis and NTM did not influence skin reactions to bovine tuberculin PPD. Avian tuberculin PPD skin reactions were larger in M. bovis-infected lions compared to uninfected ones. Since NTM co-infections are likely to influence the outcome of skin testing, stricter test interpretation criteria were applied. When test data of bovine tuberculin PPD tests were considered on their own, as for a single skin test, sensitivity increased (80.8-86.5%) but false positive rate for true negatives (18.75%) remained unchanged. Finally, the adapted skin test procedure was shown not to be impeded by persistent Feline Immunodeficiency Virus(Ple) co-infection. Copyright 2010 Elsevier B.V. All rights reserved.

  18. Evaluation of Intradermal and Subcutaneous Infusion Set Performance Under 24-Hour Basal and Bolus Conditions

    PubMed Central

    McVey, Elaine; Keith, Steven; Herr, Joshua K.; Sutter, Diane; Pettis, Ronald J.

    2015-01-01

    Background: This study sought to assess the function and delivery reliability of intradermal (ID) infusion sets used with commercial insulin pumps. Method: Healthy subjects (n = 43) were randomized to either ID or subcutaneous (SC) arms, and received basal/bolus placebo delivery for 24 hours. Subjects received 4 of 8 infusion set combinations (ID: microneedle design A or B, with 2 pump brands [Animas or MiniMed]; SC: Teflon Quickset or steel Rapid-D, Animas pump only, with or without overtaping) and were evaluated for pump occlusion alarms, fluid leakage, pain, and tissue tolerability. A novel algorithm was developed to determine flow consistency based on fluid pressure, and the duration and occurrence rate for periods of unalarmed but interrupted flow (“silent occlusions’”) were compared. Results: ID delivery was successfully maintained over the 24-hour infusion period. The number of silent occlusions was lower for ID microneedle cannula design B than A (P < .01) and lower for Rapid-D SC device compared to Quick-set (P = .03). There was no significant difference in the number of occlusion alarms between the ID and SC devices with the Animas pump. However, the pumps tested with ID devices had significantly different alarm rates (MiniMed 29.5%, Animas 0%, P < .001). Leakage and tissue tolerability were comparable across devices. Conclusion: The ID infusion set reliably delivered diluent for an extended 24-hour period in healthy subjects and was well tolerated. Silent occlusion flow interruptions could be detected in both ID and SC infusion sets using a proprietary algorithm. This algorithm is a promising method for quantitatively evaluating infusion set flow performance. PMID:26319228

  19. An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection.

    PubMed

    Soong, Lynn; Mendell, Nicole L; Olano, Juan P; Rockx-Brouwer, Dedeke; Xu, Guang; Goez-Rivillas, Yenny; Drom, Claire; Shelite, Thomas R; Valbuena, Gustavo; Walker, David H; Bouyer, Donald H

    2016-08-01

    Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d.) inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11-12 days post-infection (dpi), followed by marked hypothermia and body weight loss at 14-19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF), as well as modulatory cytokines (IL-9, IL-13). Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions.

  20. Low response to intradermal hepatitis B vaccination in incident hemodialysis patients.

    PubMed

    Medeiros, Regina H; Figueiredo, Ana Elizabeth Pl; Poli-de-Figueiredo, Carlos Eduardo; d'Avila, Domingos Otávio; de los Santos, Carlos Abaeté

    2011-03-01

    Hepatitis B (HB) may progress to cirrhosis and liver carcinoma. Its prevalence is estimated at 3.2 % in hemodialysis (HD) patients. HB vaccine when applied intramuscularly (IM) in end-stage renal disease patients often does not induce appropriate antibody titers. However, there has been suggestion for intradermal (ID) to be a more effective inoculation method. To compare the immune response to IM or ID vaccine administration on HD patients. Thirty one incident HD patients were randomly assigned alternately to IM or ID vaccine inoculation. Vaccine doses were applied at three monthly intervals, with patients being followed-up for six months. Sixteen patients were assigned to IM (40 mg/dose) and 15 to ID (4 mg/dose) vaccine administration. HB-virus surface antibody titer, hematimetric parameters, serum urea level and Kt/V were monthly evaluated. C-reactive protein, parathormone, ferritin, aminotransferases and albumin serum levels were evaluated before and at the sixth month of the initial inoculation. Urea levels were significantly higher in the ID group (P(1) = 0.031); ferritin levels were higher in the IM (P(2) = 0.037) and C-reactive protein levels tended to be higher in the ID group. An interim evaluation by the Safety Monitoring Committee recommended discontinuing the study as IM vaccination had converted 62.5% of the exposed subjects, while ID inoculation converted only 13.3%. As performed, ID applied vaccine was inferior to the IM inoculation. Such result may depend on the inoculated doses or some other factor, such as inflammation.

  1. An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection

    PubMed Central

    Rockx-Brouwer, Dedeke; Xu, Guang; Goez-Rivillas, Yenny; Drom, Claire; Shelite, Thomas R.; Valbuena, Gustavo; Walker, David H.; Bouyer, Donald H.

    2016-01-01

    Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d.) inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11–12 days post-infection (dpi), followed by marked hypothermia and body weight loss at 14–19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF), as well as modulatory cytokines (IL-9, IL-13). Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions. PMID:27479584

  2. Intradermally focused infrared laser pulses: thermal effects at defined tissue depths.

    PubMed

    Khan, Misbah Huzaira; Sink, R Kehl; Manstein, Dieter; Eimerl, David; Anderson, R Rox

    2005-04-01

    To produce controlled, spatially confined thermal effects in dermis. A 1 W, 1,500 nm fiber-coupled diode laser was focused with a high numerical aperture (NA) objective to achieve a tight optical focus within the upper dermis of skin held in contact with a glass window. The delivery optics was moved using a computer-controlled translator to generate an array of individual exposure spots. Fresh human facial skin samples were exposed to a range of pulse energies at specific focal depths, and to a range of focal depths at constant pulse energy. Cellular damage was evaluated in frozen sections using nitro-blue tetrazolium chloride (NBTC), a lactate dehydrogenase (LDH) activity stain. Loss of birefringence due to thermal denaturation of collagen was evaluated using cross-polarized light microscopy. The extent of focal thermal injury was compared with a model for photon migration (Monte Carlo Simulation), heat diffusion, and protein denaturation (Arrhenius model). Arrays of confined, microscopic intradermal foci of thermal injury were created. At high NA, epidermal damage was avoided without active cooling. Foci of thermal injury were typically 50-150 microm in diameter, elliptical, and at controllable depths from 0 to 550 microm. Both LDH inactivation and extracellular matrix denaturation were achieved. Spatially confined foci of thermal effects can be achieved by focusing a low-power infrared laser into skin. Size, depth, and density of microscopic, thermal damage foci may be arbitrarily controlled while sparing surrounding tissue. This may offer a new approach for nonablative laser therapy of dermal disorders. Copyright 2005 Wiley-Liss, Inc.

  3. Cidofovir Injection

    MedlinePlus

    ... in babies whose mothers received cidofovir injection during pregnancy. You should not use cidofovir injection while you are pregnant or plan to become pregnant unless your doctor decides that this is the best treatment for your condition.Cidofovir injection has caused tumors ...

  4. Albiglutide Injection

    MedlinePlus

    ... blood) when other medications did not control levels well enough. Albiglutide injection is not used to treat type 1 diabetes ( ... does not cure it. Continue to use albiglutide injection even if you feel well. Do not stop using albiglutide injection without talking ...

  5. Nalbuphine Injection

    MedlinePlus

    ... Your doctor may adjust your dose of nalbuphine injection during your treatment, depending on how well your pain is controlled and on the side effects that you experience. Talk to your doctor about how you are feeling ... nalbuphine injection.You may receive nalbuphine injection in a hospital, ...

  6. Liraglutide Injection

    MedlinePlus

    ... blood) when other medications did not control levels well enough. Liraglutide injection (Victoza) is not used to treat type 1 ... does not cure it. Continue to use liraglutide injection even if you feel well. Do not stop using liraglutide injection without talking ...

  7. Meperidine Injection

    MedlinePlus

    ... Your doctor may adjust your dose of meperidine injection during your treatment, depending on how well your pain is controlled and on the side effects that you experience. Talk to your doctor about how you are feeling ... meperidine injection.If you have used meperidine injection for longer ...

  8. Dulaglutide Injection

    MedlinePlus

    ... blood) when other medications did not control levels well enough. Dulaglutide injection is not used to treat type 1 diabetes ( ... does not cure it. Continue to use dulaglutide injection even if you feel well. Do not stop using dulaglutide injection without talking ...

  9. Morphine Injection

    MedlinePlus

    ... Your doctor may adjust your dose of morphine injection during your treatment, depending on how well your pain is controlled and on the side effects that you experience. Talk to your doctor about how you are feeling ... with morphine injection.If you have used morphine injection for longer ...

  10. Busulfan Injection

    MedlinePlus

    Busulfex® Injection ... Busulfan injection is used to treat a certain type of chronic myelogenous leukemia (CML; a type of cancer of ... of 16 doses) before bone marrow transplant.Busulfan injection may cause seizures during therapy with the medication. ...

  11. Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults.

    PubMed

    Troy, Stephanie B; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne

    2015-06-15

    Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody titers. We randomly assigned 231 adults with well-controlled human immunodeficiency virus infection at a ratio of 2:2:2:1 to receive 40% of the standard dose of IPV intradermally, 20% of the standard dose intradermally, the full standard dose intramuscularly, or 40% of the standard dose intramuscularly. Intradermal vaccination was done using the NanoPass MicronJet600 microneedle device. Baseline immunity was 87%, 90%, and 66% against poliovirus serotypes 1, 2, and 3, respectively. After vaccination, antibody titers increased a median of 64-fold. Vaccine response to 40% of the standard dose administered intradermally was comparable to that of the standard dose of IPV administered intramuscularly and resulted in higher (although not significantly) antibody titers. Intradermal administration had higher a incidence of local side effects (redness and itching) but a similar incidence of systemic side effects and was preferred by study participants over intramuscular administration. A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Folate Receptor-Targeted Multimodality Imaging of Ovarian Cancer in a Novel Syngeneic Mouse Model

    PubMed Central

    2015-01-01

    A new transplantable ovarian tumor model is presented using a novel folate receptor (FR) positive, murine ovarian cancer cell line that emulates the human disease and induces widespread intraperitoneal (i.p.) tumors in immunocompetent mice within 4–8 weeks of implantation. Tumor development was monitored using a new positron emission tomography (PET) FR-targeting reporter with PET/computerized tomography (PET/CT) and fluorescence molecular tomography (FMT) using a commercial FR-targeting reporter. Conventional structural magnetic resonance imaging (MRI) was also performed. Adult female C57BL/6 mice were injected i.p. with 6 × 106 MKP-L FR+ cells. Imaging was performed weekly beginning 2 weeks after tumor induction. The albumin-binding, FR-targeting ligand cm09 was radiolabeled with the positron emitter 68Ga and used to image the tumors with a small animal PET/CT. The FR-reporter FolateRSense 680 (PerkinElmer) was used for FMT and flow cytometry. Preclinical MRI (7 T) without FR-targeting was compared with the PET and FMT molecular imaging. Tumors were visible by all three imaging modalities. PET/CT had the highest imaging sensitivity at 3–3.5 h postadministration (mean %IA/g mean > 6) and visualized tumors earlier than the other two modalities with lower kidney uptake (mean %IA/g mean < 17) than previously reported FR-targeting agents in late stage disease. FMT showed relatively low FR-targeted agent in the bladder and kidneys, but yielded the lowest anatomical image resolution. MRI produced the highest resolution images, but it was difficult to distinguish tumors from abdominal organs during early progression since a FR-targeting MRI reporter was not used. Nevertheless, there was good correlation of imaging biomarkers between the three modalities. Tumors in the mouse ovarian cancer model could be detected using FR-targeted imaging as early as 2 weeks post i.p. injection of tumor cells. An imaging protocol should combine one or more of the modalities, e

  13. Humanized mice efficiently engrafted with fetal hepatoblasts and syngeneic immune cells develop human monocytes and NK cells

    PubMed Central

    Billerbeck, Eva; Mommersteeg, Michiel C.; Shlomai, Amir; Xiao, Jing W.; Andrus, Linda; Bhatta, Ankit; Vercauteren, Koen; Michailidis, Eleftherios; Dorner, Marcus; Krishnan, Anuradha; Charlton, Michael R.; Chiriboga, Luis; Rice, Charles M.; de Jong, Ype P.

    2016-01-01

    Background & Aims Human liver chimeric mice are useful models of human hepatitis virus infection, including hepatitis B and C virus infections. Independently, immunodeficient mice reconstituted with CD34+ hematopoietic stem cells (HSC) derived from fetal liver reliably develop human T and B lymphocytes. Combining these systems has long been hampered by inefficient liver reconstitution of human fetal hepatoblasts. Our study aimed to enhance hepatoblast engraftment in order to create a mouse model with syngeneic human liver and immune cells. Methods The effects of human oncostatin-M administration on fetal hepatoblast engraftment into immunodeficient fah−/− mice was tested. Mice were then transplanted with syngeneic human hepatoblasts and HSC after which human leukocyte chimerism and functionality were analyzed by flow cytometry, and mice were challenged with HBV. Results Addition of human oncostatin-M enhanced human hepatoblast engraftment in immunodeficient fah−/− mice by 5–100 fold. In contrast to mice singly engrafted with HSC, which predominantly developed human T and B lymphocytes, mice co-transplanted with syngeneic hepatoblasts also contained physiological levels of human monocytes and natural killer cells. Upon infection with HBV, these mice displayed rapid and sustained viremia. Conclusions Our study provides a new mouse model with improved human fetal hepatoblast engraftment and an expanded human immune cell repertoire. With further improvements, this model may become useful for studying human immunity against viral hepatitis. Lay summary Important human pathogens such as hepatitis B virus, hepatitis C virus and human immunodeficiency virus only infect human cells which complicates the development of mouse models for the study of these pathogens. One way to make mice permissive for human pathogens is the transplantation of human cells into immune-compromised mice. For instance, the transplantation of human liver cells will allow the infection of

  14. An improved syngeneic orthotopic murine model of human breast cancer progression.

    PubMed

    Rashid, Omar M; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine; Schaum, Julia; Yamada, Akimitsu; Terracina, Krista P; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2014-10-01

    Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous (OP) injection in the area of the nipple, or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. ODV produced less variable-sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development .

  15. Neuroimmune mechanisms of behavioral alterations in a syngeneic murine model of human papilloma virus-related head and neck cancer.

    PubMed

    Vichaya, Elisabeth G; Vermeer, Daniel W; Christian, Diana L; Molkentine, Jessica M; Mason, Kathy A; Lee, John H; Dantzer, Robert

    2017-05-01

    Patients with cancer often experience a high symptom burden prior to the start of treatment. As disease- and treatment-related neurotoxicities appear to be additive, targeting disease-related symptoms may attenuate overall symptom burden for cancer patients and improve the tolerability of treatment. It has been hypothesized that disease-related symptoms are a consequence of tumor-induced inflammation. We tested this hypothesis using a syngeneic heterotopic murine model of human papilloma virus (HPV)-related head and neck cancer. This model has the advantage of being mildly aggressive and not causing cachexia or weight loss. We previously showed that this tumor leads to increased IL-6, IL-1β, and TNF-α expression in the liver and increased IL-1β expression in the brain. The current study confirmed these features and demonstrated that the tumor itself exhibits high inflammatory cytokine expression (e.g., IL-6, IL-1β, and TNF-α) compared to healthy tissue. While there is a clear relationship between cytokine levels and behavioral deficits in this model, the behavioral changes are surprisingly mild. Therefore, we sought to confirm the relationship between behavior and inflammation by amplifying the effect using a low dose of lipopolysaccharide (LPS, 0.1mg/kg). In tumor-bearing mice LPS induced deficits in nest building, tail suspension, and locomotor activity approximately 24h after LPS. However, these mice did not display an exacerbation of LPS-induced weight loss, anorexia, or anhedonia. Further, while heightened serum IL-6 was observed there was minimal priming of liver or brain cytokine expression. Next we sought to inhibit tumor-induced burrowing deficits by reducing inflammation using minocycline. Minocycline (∼50mg/kg/day in drinking water) was able to attenuate tumor-induced inflammation and burrowing deficits. These data provide evidence in favor of an inflammatory-like mechanism for the behavioral alterations associated with tumor growth in a syngeneic

  16. Intradermal versus intramuscular hepatitis B vaccination in hemodialysis patients: a prospective open-label randomized controlled trial in nonresponders to primary vaccination.

    PubMed

    Barraclough, Katherine A; Wiggins, Kathryn J; Hawley, Carmel M; van Eps, Carolyn L; Mudge, David W; Johnson, David W; Whitby, Michael; Carpenter, Sally; Playford, E Geoffrey

    2009-07-01

    Primary hepatitis B virus (HBV) vaccination through the intramuscular (IM) route is less efficacious in dialysis patients than in the general population. Previous studies suggest improved seroconversion with intradermal (ID) vaccination. Prospective open-label randomized controlled trial. Hemodialysis patients nonresponsive to primary HBV vaccination. Revaccination with either ID (10 microg of vaccine every week for 8 weeks) [DOSAGE ERROR CORRECTED] or IM (40 microg of vaccine at weeks 1 and 8) HBV vaccine . proportion of patients achieving HBV surface antibody (anti-HBs) titer of 10 IU/L or greater within 2 months of vaccination course. time to seroconversion, predictors of seroconversion, peak antibody titer, duration of seroprotection, and safety and tolerability of vaccine. Anti-HBs titer to 24 months. 59 patients were analyzed. Seroconversion rates were 79% ID versus 40% IM (P = 0.002). The unadjusted odds ratio for seroconversion for ID versus IM was 5.5 (95% confidence interval [CI], 1.6 to 18.4) and increased with adjustment for baseline differences. The only factor predictive of seroconversion was the ID vaccination route. The geometric mean peak antibody titer was significantly greater in the ID versus IM group: 239 IU/L (95% CI, 131 to 434) versus 78 IU/L (95% CI, 36 to 168; P < 0.001). There was a trend toward longer duration of seroprotection with ID vaccination. ID vaccine was safe and well tolerated. Inability to distinguish whether the mechanism of the greater efficacy of ID vaccination was the cumulative effect of multiple injections or route of administration; use of anti-HBs as a surrogate marker of protection; lack of evidence of long-term protection. Significantly greater seroconversion rates and peak antibody titers can be achieved with ID compared with IM vaccination in hemodialysis patients nonresponsive to primary vaccination. ID vaccination should become the standard of care in this setting.

  17. Intradermal immunization with ovalbumin-loaded poly-epsilon-caprolactone microparticles conferred protection in ovalbumin-sensitized allergic mice.

    PubMed

    Roman, B S; Espuelas, S; Gómez, S; Gamazo, C; Sanz, M L; Ferrer, M; Irache, J M

    2007-02-01

    Although immunotherapy has been reported as the only treatment able to revert the T-helper type 2 (Th2) response, its administration has some disadvantages such as the requirement of multiple doses, possible side-effects provoked by conventional adjuvants and the risk of suffering an anaphylactic shock. For these reasons, drug-delivery systems appear to be a promising strategy due to its ability to (i) transport the allergens, (ii) protect them from degradation, (iii) decrease the number of administrations and (iv) act as immuno-adjuvants. The aim of this work was to evaluate the properties of poly-epsilon-caprolactone (PCL) microparticles as adjuvants in immunotherapy using ovalbumin (OVA) as an allergen model. For this purpose, the protection capacity of these microparticles (OVA PCL) against OVA allergy was studied in a murine model. The humoral and cellular-induced immune response generated by OVA encapsulated into PCL microparticles was studied by immunizing BALB/c mice intradermically. Also, OVA-sensitized mice were treated with OVA PCL and OVA adsorbed to aluminium hydroxide (OVA-Alum). Fifteen days after therapy, animals were challenged with OVA and different signs of anaphylactic shock were evaluated. One single shot by an intradermal route with OVA PCL resulted in a Th2-type immune response. In OVA-sensitized mice, treatment with OVA PCL elicited high OVA-specific IgG but low levels of IgE. Furthermore, OVA PCL mice group displayed lower levels of serum histamine and higher survival rate in comparison with the positive control group. The anaphylactic shock suffered by OVA PCL-treated mice was weaker than the one induced in the OVA-Alum group. Hence, the intradermal immunization with OVA PCL microparticles induced hyposensitization in OVA-allergic mice.

  18. Regulation of immune responses aginst the syngeneic ADJ-PC-5 plasmacytoma in BALB-c mice. III. Induction of specific T suppressor cells to the BALB/c plasmacytoma ADJ-PC-5 during early stages of tumorigenesis.

    PubMed Central

    Haubeck, H D; Kölsch, E

    1982-01-01

    Initial stages of tumour growth are not easily accessible to investigation. Therefore an experimental procedure was developed to mimic tumorigenesis as closely as possible. BALB/c mice received intraperitoneally exponentially increasing numbers of irradiated syngeneic ADJ-PC-5 plasmacytoma cells. The initial injection began with two cells per mouse and according to the generation time of this tumour, subsequent doses were doubled until mice had received up to 10(5) tumour cells. At various stages of treatment, peritoneal exudate cells (PEC) and spleen cells (SC) were tested for either cytotoxicity or specific suppression of induction of a primary in vitro T-cell cytotoxic response (CTL) of BALB/c spleen cells against ADJ-PC-5 plasmacytoma cells. No cytotoxic PEC were found. Instead, PEC from mice in which the final tumour cells number had reached or exceeded 10(3) irradiated ADJ-PC-5 cells, induced complete suppression of this primary in vitro CTL. Specificity was found both in the induction and effector phase of suppression. Specific suppression was mediated by Thy-1.2+ cells and amplified by non-specific suppression through adherent cells. The data arae discussed in context with previous findings on the in vivo immunogenicity and tolerogenicity of the ADJ-PC-5 plasmacytoma. They suggest that induction of T suppressor (Ts) cells might be an early event in tumorigenesis. PMID:6215340

  19. Pharmacokinetic studies of mouse monoclonal antibodies to a rat colon carcinoma: I. Comparison of biodistribution in normal rats, syngeneic tumor-bearing rats, or tumor-bearing nude mice

    SciTech Connect

    Laborda, J.; Douillard, J.Y.; Burg, C.; Lizzio, E.F.; Ridge, J.; Levenbook, I.; Hoffman, T. )

    1990-06-01

    The pharmacokinetics of two iodine-131-({sup 131}I) labeled murine anti-rat colon carcinoma monoclonal antibodies (D3 and E4) were compared in normal Sprague Dawley rats, syngeneic BDIX rats, or nude mice bearing that tumor. Results of antibody uptake after i.v. administration were analyzed in terms of accumulation and localization indices for normal tissues and tumor. Statistically significant differences between rat and mouse tissue biodistribution were found. D3, which reacts in vitro with the tumor and several normal rat tissues, cleared quickly from the blood of rats and was specifically targeted to several normal tissues, notably the lung. Virtually no targeting to the tumor was observed. Nude mice, however, showed a slower blood clearance and specific antibody targeting only in the tumor. Similar results were seen after injection of another antibody, E4, which is tumor-specific in vitro. Data suggest that studies on the xenogeneic nude mouse model may not necessarily be relevant to the choice of monoclonal antibodies for clinical diagnostic imaging or therapy.

  20. Comparative Study of Efficacy and Safety of Botulinum Toxin a Injections and Subcutaneous Curettage in the Treatment of Axillary Hyperhidrosis

    PubMed Central

    Budamakuntla, Leelavathy; Loganathan, Eswari; George, Anju; Revanth, BN; Sankeerth, V; Sarvjnamurthy, Sacchidananda Aradhya

    2017-01-01

    Background: Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. Aims and Objectives: The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and subcutaneous curettage of sweat glands in the other axilla of the same patient with axillary hyperhidrosis. Materials and Methods: Twenty patients (40 axillae) received intradermal BtxA injections on the right side (20 axillae) and underwent tumescent subcutaneous curettage of sweat glands on the left side (20 axillae). Sweat production rate was measured using gravimetry analyses at baseline and at 3 months after the procedure. Subjective analyses were done using hyperhidrosis disease severity scale (HDSS) score at baseline, at 3rd and 6th month after the procedure. Results: At 3 months post-treatment, the resting sweat rate in the toxin group improved by 80.32% versus 79.79% in the subcutaneous curettage method (P = 0.21). Exercise-induced sweat rate in the toxin group improved by 88.76% versus 88.8% in the subcutaneous curettage group (P = 0.9). There was a significant difference in the HDSS score after treatment with both the modalities. There were no adverse events with BtxA treatment compared to very minor adverse events with the surgical method. Conclusion: Both intradermal BtxA injections and tumescent subcutaneous curettage of sweat glands had a significant decrease in the sweat rates with no significant difference between the two modalities. Hence, in resource poor settings where affordability of BtxA injection is a constraint, subcutaneous curettage of sweat glands can be preferred which has been found equally effective with no or minimal adverse events. PMID

  1. Comparative Study of Efficacy and Safety of Botulinum Toxin a Injections and Subcutaneous Curettage in the Treatment of Axillary Hyperhidrosis.

    PubMed

    Budamakuntla, Leelavathy; Loganathan, Eswari; George, Anju; Revanth, B N; Sankeerth, V; Sarvjnamurthy, Sacchidananda Aradhya

    2017-01-01

    Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and subcutaneous curettage of sweat glands in the other axilla of the same patient with axillary hyperhidrosis. Twenty patients (40 axillae) received intradermal BtxA injections on the right side (20 axillae) and underwent tumescent subcutaneous curettage of sweat glands on the left side (20 axillae). Sweat production rate was measured using gravimetry analyses at baseline and at 3 months after the procedure. Subjective analyses were done using hyperhidrosis disease severity scale (HDSS) score at baseline, at 3(rd) and 6(th) month after the procedure. At 3 months post-treatment, the resting sweat rate in the toxin group improved by 80.32% versus 79.79% in the subcutaneous curettage method (P = 0.21). Exercise-induced sweat rate in the toxin group improved by 88.76% versus 88.8% in the subcutaneous curettage group (P = 0.9). There was a significant difference in the HDSS score after treatment with both the modalities. There were no adverse events with BtxA treatment compared to very minor adverse events with the surgical method. Both intradermal BtxA injections and tumescent subcutaneous curettage of sweat glands had a significant decrease in the sweat rates with no significant difference between the two modalities. Hence, in resource poor settings where affordability of BtxA injection is a constraint, subcutaneous curettage of sweat glands can be preferred which has been found equally effective with no or minimal adverse events.

  2. An Improved Syngeneic Orthotopic Murine Model of Human Breast Cancer Progression

    PubMed Central

    Rashid, Omar M.; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine; Schaum, Julia; Yamada, Akimitsu; Terracina, Krista P.; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2014-01-01

    Purpose Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Methods Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous injection in the area of the nipple (OP), or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. Results ODV produced less variable sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. Conclusions ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development. PMID:25200444

  3. Temozolomide does not impair gene therapy-mediated antitumor immunity in syngeneic brain tumor models

    PubMed Central

    Wibowo, Mia; Ahlzadeh, Gabrielle E; Puntel, Mariana; Ghiasi, Homayon; Kamran, Neha; Paran, Christopher; Lowenstein, Pedro R; Castro, Maria G

    2014-01-01

    Purpose Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults. Chemotherapy with temozolomide (TMZ) significantly prolongs the survival of GBM patients. However, the 3-year survival is still ~5%. Herein we combined intratumoral administration of an adenoviral vector expressing Flt3L (Ad-Flt3L) with systemic TMZ in order to assess its impact on therapeutic efficacy. Experimental Design Wild type or immunodeficient mice bearing intracranial GBM or metastatic melanoma were treated with an intratumoral injection of Ad-Flt3L alone or in combination with the conditionally cytotoxic enzyme thymidine kinase (Ad-TK), followed by systemic administration of ganciclovir and TMZ. We monitored survival and measured the tumor-infiltrating immune cells. Results While treatment with TMZ alone led to a small improvement in median survival, when used in combination with gene therapy-mediated immunotherapy it significantly increased the survival of tumor-bearing mice. The anti-tumor effect was further enhanced by concomitant intratumoral administration of Ad-TK, leading to 50–70% long-term survival in all tumor models. Although TMZ reduced the content of T cells in the tumor, this did not affect the therapeutic efficacy. The anti-tumor effect of Ad-Flt3L+Ad-TK+TMZ required an intact immune system, since the treatment failed when administered to KO mice that lacked lymphocytes or dendritic cells. Conclusions Our results challenge the notion that chemotherapy leads to a state of immune-suppression which impairs the ability of the immune system to mount an effective anti-tumor response. Our work indicates that TMZ does not inhibit antitumor immunity and supports its clinical implementation in combination with immune-mediated therapies. PMID:24501391

  4. [Comparison of intradermal and prick tests based on samples of the most common allergens in the Zadar region].

    PubMed

    Mazzi, A

    1995-01-01

    The practical clinical problem of evaluating the significance of positive dermal tests is present in daily in vivo diagnoses in allergology and clinical immunology. Our research was aimed at a comparison of the two methods of dermal tests, namely, intradermal (i.d.) and prick tests, based on a sample of the most common allergenics in the Zadar region. The intradermal method was applied to a group of 664 patients, the prick test was used in a group of 641 patients, and 60 patients were examined using both methods. In the tests allergens from extracts of Dermatophagoides pteronyssinus, tree, weeds and grass pollens, dust, feathers, eggs, milk, flour, meat and fish from the Zagreb Institute of Immunology were used. A solution of histamine chloride and buffer saline containing 50% glycerol, prepared by the same Institute was used as a control. We considered a positive reaction to the intradermal test to have occurred when an urticaria of 5 or more mm radius with surrounding inflammation developed. A reaction to the prick method was considered to have taken place when an urticaria of 3 or more mm radius, together with surrounding inflammation resulted. A positive reaction was shown in 30% of those to whom the prick test was applied, and in 32% of those to whom intradermal tests were used, which represents 0.11-0.13% of the total adult population of the region of Zadar. A positive reaction to a single allergen was shown in 43% of the patients tested by i.d. test, and in 52% of the patients tested with the prick method. The most common oversensitivity with both methods was shown to Dermatophagoides pteronyssinus (86% i.d., and 56% prick, respectively). Among the pollen allergenics the most common reaction was to grass pollen (47% i.d., 65% prick). With patients who were tested with both methods (60 patients), there were also differences in results. An equal dermal reaction to both tests was shown in 32% of the patients, minor differences were present in 45%, and

  5. In Vivo Safety, Biodistribution and Antitumor Effects of uPAR Retargeted Oncolytic Measles Virus in Syngeneic Cancer Models

    PubMed Central

    Jing, Yuqi; Zaias, Julia; Duncan, Robert; Russell, Stephen J.; Merchan, Jaime R.

    2014-01-01

    The urokinase receptor (uPAR) is a clinically relevant target for novel biological therapies. We have previously rescued oncolytic measles viruses fully retargeted against human (MV-h-uPA) or murine (MV-m-uPA) uPAR. Here, we investigated the in vivo effects of systemic administration of MV-m-uPA in immunocompetent cancer models. MV-m-uPA induced in vitro cytotoxicity and replicated in a receptor dependent manner in murine mammary (4T1), and colon (MC-38 and CT-26) cancer cells. Intravenous administration of MV-m-uPA to 4T1 tumor bearing mice was not associated with significant clinical or laboratory toxicity. Higher MV-N RNA copy numbers were detected in primary tumors, and viable viral particles were recovered from tumor bearing tissues only. Non-tumor bearing organs did not show histological signs of viral induced toxicity. Serum anti-MV antibodies were detected at day 14 of treatment. Immunohistochemistry and immunofluorescence studies confirmed successful tumor targeting and demonstrated enhanced MV-m-uPA induced tumor cell apoptosis in treated, compared to control mice. Significant antitumor effects and prolonged survival were observed after systemic administration of MV-m-uPA in colon (CT-26) and mammary (4T1) cancer models. The above results demonstrate safety and feasibility of uPAR targeting by an oncolytic virus, and confirm significant antitumor effects in highly aggressive syngeneic immunocompetent cancer models. PMID:24430235

  6. Potent activity of soluble B7RP-1-Fc in therapy of murine tumors in syngeneic hosts.

    PubMed

    Ara, Gulshan; Baher, Angelo; Storm, Neal; Horan, Tom; Baikalov, Claudia; Brisan, Emil; Camacho, Reuben; Moore, Alison; Goldman, Hartt; Kohno, Tadahiko; Cattley, Russell C; Van, Gwyneth; Gaida, Kevin; Zhang, Ming; Whoriskey, John S; Fong, David; Yoshinaga, Steven K

    2003-02-10

    We have characterized a receptor:ligand pair, ICOS:B7RP-1, that is structurally and functionally related to CD28:B7.1/2. We reported previously that B7RP-1 costimulates T cell proliferation and immune responses (Yoshinaga et al., Nature 1999;402:827-32; Guo et al., J Immunol 2001;166:5578-84; Yoshinaga et al., Int Immunol 2000;12:1439-47). We report that B7RP-1-Fc causes rejection or growth inhibition of Meth A, SA-1 and EMT6 tumors in syngeneic mice. Established Meth A tumors were rejected effectively with a single dose of B7RP-1-Fc, however, the treatment was less effective on larger tumors. Mice that rejected Meth A tumors previously by Day 30, also rejected a subsequent Meth A challenge on Day 60, without additional B7RP-1-Fc treatment, indicating a long-lived memory response. Tumor cells believed to be less immunogenic, such as P815 and EL-4 cells, were less responsive to this treatment. The EL-4 responsiveness to the B7RP-1-Fc treatment was enhanced, however, by pre-treatment of the mice with cyclophosphamide. As expected, T cells appeared to be targeted by B7RP-1-Fc treatment. Thus, the administration of soluble B7RP-1-Fc may have therapeutic value in generating or enhancing anti-tumor activity in a clinical setting. Copyright 2002 Wiley-Liss, Inc.

  7. Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells.

    PubMed

    Sy, M S; Bach, B A; Brown, A; Nisonoff, A; Benacerraf, B; Greene, M I

    1979-11-01

    Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross-reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA-specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T-cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen-specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.

  8. Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells

    PubMed Central

    1979-01-01

    Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross- reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA- specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T- cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen- specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene. PMID:91657

  9. Enhancement of the pro-apoptotic properties of Newcastle disease virus promotes tumor remission in syngeneic murine cancer models

    PubMed Central

    Cuadrado-Castano, Sara; Ayllon, Juan; Mansour, Mena; de la Iglesia-Vicente, Janis; Jordan, Stefan; Tripathi, Shashank; García-Sastre, Adolfo; Villar, Enrique

    2015-01-01

    Newcastle disease virus (NDV) is considered a promising agent for cancer therapy due to its oncolytic properties. These include preferential replication in transformed cells, induction of innate and adaptive immune responses within tumors and cytopathic effects in infected tumor cells due to the activation of apoptosis. In order to enhance the latter and thus possibly enhance the overall oncolytic activity of NDV, we generated a recombinant NDV encoding the human TNF receptor Fas (rNDV-B1/Fas). rNDV-B1/Fas replicates to similar titers as its wild type (rNDV-B1) counterpart, however overexpression of Fas in infected cells leads to higher levels of cytotoxicity correlated with faster and increased apoptosis responses in which both the intrinsic and extrinsic pathways are activated earlier. Furthermore, in vivo studies in syngeneic murine melanoma model show an enhancement of the oncolytic properties of rNDV-B1/Fas, with major improvements in survival and tumor remission. Altogether, our data suggest that up-regulation of the pro-apoptotic function of NDV is a viable approach to enhance its anti-tumor properties, and adds to the currently known, rationally-based strategies to design optimized therapeutic viral vectors for the treatment of cancer. PMID:25761895

  10. Tumourigenicity and Immunogenicity of Induced Neural Stem Cell Grafts Versus Induced Pluripotent Stem Cell Grafts in Syngeneic Mouse Brain

    PubMed Central

    Gao, Mou; Yao, Hui; Dong, Qin; Zhang, Hongtian; Yang, Zhijun; Yang, Yang; Zhu, Jianwei; Xu, Minhui; Xu, Ruxiang

    2016-01-01

    Along with the development of stem cell-based therapies for central nervous system (CNS) disease, the safety of stem cell grafts in the CNS, such as induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs), should be of primary concern. To provide scientific basis for evaluating the safety of these stem cells, we determined their tumourigenicity and immunogenicity in syngeneic mouse brain. Both iPSCs and embryonic stem cells (ESCs) were able to form tumours in the mouse brain, leading to tissue destruction along with immune cell infiltration. In contrast, no evidence of tumour formation, brain injury or immune rejection was observed with iNSCs, neural stem cells (NSCs) or mesenchymal stem cells (MSCs). With the help of gene ontology (GO) enrichment analysis, we detected significantly elevated levels of chemokines in the brain tissue and serum of mice that developed tumours after ESC or iPSC transplantation. Moreover, we also investigated the interactions between chemokines and NF-κB signalling and found that NF-κB activation was positively correlated with the constantly rising levels of chemokines, and vice versa. In short, iNSC grafts, which lacked any resulting tumourigenicity or immunogenicity, are safer than iPSC grafts. PMID:27417157

  11. Biogenicity and Syngeneity of Organic Matter in Ancient Sedimentary Rocks: Recent Advances in the Search for Evidence of Past Life

    NASA Astrophysics Data System (ADS)

    Oehler, Dorothy Z.; Cady, Sherry L.

    2014-08-01

    The past decade has seen an explosion of new technologies for assessment of biogenicity and syngeneity of carbonaceous material within sedimentary rocks. Advances have been made in techniques for analysis of in situ organic matter as well as for extracted bulk samples of soluble and insoluble (kerogen) organic fractions. The in situ techniques allow analysis of micrometer-to-sub-micrometer-scale organic residues within their host rocks and include Raman and fluorescence spectroscopy/imagery, confocal laser scanning microscopy, and forms of secondary ion/laser-based mass spectrometry, analytical transmission electron microscopy, and X-ray absorption microscopy/spectroscopy. Analyses can be made for chemical, molecular, and isotopic composition coupled with assessment of spatial relationships to surrounding minerals, veins, and fractures. The bulk analyses include improved methods for minimizing contamination and recognizing syngenetic constituents of soluble organic fractions as well as enhanced spectroscopic and pyrolytic techniques for unlocking syngenetic molecular signatures in kerogen. Together, these technologies provide vital tools for the study of some of the oldest and problematic carbonaceous residues and for advancing our understanding of the earliest stages of biological evolution on Earth and the search for evidence of life beyond Earth. We discuss each of these new technologies, emphasizing their advantages and disadvantages, applications, and likely future directions.

  12. Diabetes Is Reversed in a Murine Model by Marginal Mass Syngeneic Islet Transplantation Using a Subcutaneous Cell Pouch Device

    PubMed Central

    Pepper, Andrew R.; Pawlick, Rena; Gala-Lopez, Boris; MacGillivary, Amanda; Mazzuca, Delfina M.; White, David J. G.; Toleikis, Philip M.; Shapiro, A. M. James

    2015-01-01

    Background Islet transplantation is a successful β-cell replacement therapy for selected patients with type 1 diabetes mellitus. Although high rates of early insulin independence are achieved routinely, long-term function wanes over time. Intraportal transplantation is associated with procedural risks, requires multiple donors, and does not afford routine biopsy. Stem cell technologies may require potential for retrievability, and graft removal by hepatectomy is impractical. There is a clear clinical need for an alternative, optimized transplantation site. The subcutaneous space is a potential substitute, but transplantation of islets into this site has routinely failed to reverse diabetes. However, an implanted device, which becomes prevascularized before transplantation, may alter this equation. Methods Syngeneic mouse islets were transplanted subcutaneously within Sernova Corp's Cell Pouch (CP). All recipients were preimplanted with CPs 4 weeks before diabetes induction and transplantation. After transplantation, recipients were monitored for glycemic control and glucose tolerance. Results Mouse islets transplanted into the CP routinely restored glycemic control with modest delay and responded well to glucose challenge, comparable to renal subcapsular islet grafts, despite a marginal islet dose, and normoglycemia was maintained until graft explantation. In contrast, islets transplanted subcutaneously alone failed to engraft. Islets within CPs stained positively for insulin, glucagon, and microvessels. Conclusions The CP is biocompatible, forms an environment suitable for islet engraftment, and offers a potential alternative to the intraportal site for islet and future stem cell therapies. PMID:26308506

  13. Biogenicity and Syngeneity of Organic Matter in Ancient Sedimentary Rocks: Recent Advances in the Search for Evidence of Past Life

    SciTech Connect

    Oehler, Dorothy Z.; Cady, Sherry L.

    2014-12-01

    he past decade has seen an explosion of new technologies for assessment of biogenicity and syngeneity of carbonaceous material within sedimentary rocks. Advances have been made in techniques for analysis of in situ organic matter as well as for extracted bulk samples of soluble and insoluble (kerogen) organic fractions. The in situ techniques allow analysis of micrometer-to-sub-micrometer-scale organic residues within their host rocks and include Raman and fluorescence spectroscopy/imagery, confocal laser scanning microscopy, and forms of secondary ion/laser-based mass spectrometry, analytical transmission electron microscopy, and X-ray absorption microscopy/spectroscopy. Analyses can be made for chemical, molecular, and isotopic composition coupled with assessment of spatial relationships to surrounding minerals, veins, and fractures. The bulk analyses include improved methods for minimizing contamination and recognizing syngenetic constituents of soluble organic fractions as well as enhanced spectroscopic and pyrolytic techniques for unlocking syngenetic molecular signatures in kerogen. Together, these technologies provide vital tools for the study of some of the oldest and problematic carbonaceous residues and for advancing our understanding of the earliest stages of biological evolution on Earth and the search for evidence of life beyond Earth. We discuss each of these new technologies, emphasizing their advantages and disadvantages, applications, and likely future directions.

  14. Comparison of the immunogenicity and safety of a split-virion, inactivated, trivalent influenza vaccine (Fluzone®) administered by intradermal and intramuscular route in healthy adults.

    PubMed

    Frenck, Robert W; Belshe, Robert; Brady, Rebecca C; Winokur, Patricia L; Campbell, James D; Treanor, John; Hay, Christine M; Dekker, Cornelia L; Walter, Emmanuel B; Cate, Thomas R; Edwards, Kathryn M; Hill, Heather; Wolff, Mark; Leduc, Tom; Tornieporth, Nadia

    2011-08-05

    The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18-64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system (BD Soluvia™ Microinjection System), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18-49 years [N=814] and 50-64 years [N=778]. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50-64 years of age, the 6μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard

  15. Hydromorphone Injection

    MedlinePlus

    ... Your doctor may adjust your dose of hydromorphone injection during your treatment, depending on how well your pain is controlled and on the side ... to have pain after you finish the hydromorphone injection, call your doctor.It ... you are taking, as well as any products such as vitamins, minerals, or ...

  16. Ixabepilone Injection

    MedlinePlus

    ... doctor will order laboratory tests to see how well your liver is working before and during your treatment. If the tests show that you have liver problems, your doctor will probably not give you ixabepilone injection and capecitabine (Xeloda). Treatment with both ixabepilone injection ...

  17. Romidepsin Injection

    MedlinePlus

    ... group of cancers of the immune system that first appear as skin rashes) in people who have already been treated with at least one other medication given by mouth or by injection. Romidepsin injection is in a class of medications called histone deacetylase (HDAC) inhibitors. It ...

  18. Nusinersen Injection

    MedlinePlus

    Nusinersen injection is used for the treatment of spinal muscular atrophy (an inherited condition that reduces muscle strength and movement). Nusinersen injection is in a class of medications called antisense ... a certain protein necessary for the muscles and nerves to work normally.

  19. Comparative efficacy of bilastine, desloratadine and rupatadine in the suppression of wheal and flare response induced by intradermal histamine in healthy volunteers.

    PubMed

    Antonijoan, Rosa; Coimbra, Jimena; García-Gea, Consuelo; Puntes, Montserrat; Gich, Ignasi; Campo, Cristina; Valiente, Román; Labeaga, Luis

    2017-01-01

    To compare the peripheral antihistaminic activity of bilastine, rupatadine and desloratadine in inhibiting the histamine-induced wheal and flare (W&F) response. Twenty-four healthy volunteers aged 18-40 years participated in this crossover, randomized, double-blind, placebo-controlled clinical study. Subjects received single doses of bilastine 20 mg, desloratadine 5 mg, rupatadine 10 mg and placebo. W&F responses induced by intradermal injection of histamine 5 μg were evaluated before treatment (basal value) and at 0.5, 1, 2, 4, 6, 9, 12 and 24 hours after treatment. Fifteen minutes after histamine injection, W&F surface areas (cm(2)) were quantified using the Visitrak System. Itching sensation was evaluated using a 100 mm visual analog scale. EudraCT number: 2015-000790-13. The primary outcome measure was the percentage reduction in W&F areas after each active treatment compared with corresponding basal values. Bilastine induced the greatest inhibition in wheal area and was significantly superior to desloratadine and rupatadine from 1 to 12 hours (both p < .001). Rupatadine and desloratadine were better than placebo without differences between them. Maximum wheal inhibition occurred at 6 hours (bilastine 83%, desloratadine 38%, rupatadine 37%). Onset of action was 1 hour for bilastine and 4 hours for desloratadine and rupatadine. Bilastine was significantly superior to desloratadine and rupatadine for flare inhibition from 1-24 hours (both p < .001) with an onset of action at 30 minutes. Bilastine was significantly better than desloratadine (2-12 hours; at least p < .05) and rupatadine (2-9 hours; at least p < .01) for reducing itching sensation. Neither desloratadine nor rupatadine significantly reduced itching compared to placebo. All active treatments were well tolerated. Bilastine 20 mg induced significantly greater inhibition of the W&F response compared with desloratadine 5 mg and rupatadine 10 mg throughout

  20. Musculoskeletal Injection

    PubMed Central

    Wittich, Christopher M.; Ficalora, Robert D.; Mason, Thomas G.; Beckman, Thomas J.

    2009-01-01

    Patients commonly present to primary care physicians with musculoskeletal symptoms. Clinicians certified in internal medicine must be knowledgeable about the diagnosis and management of musculoskeletal diseases, yet they often receive inadequate postgraduate training on this topic. The musculoskeletal problems most frequently encountered in our busy injection practice involve, in decreasing order, the knees, trochanteric bursae, and glenohumeral joints. This article reviews the clinical presentations of these problems. It also discusses musculoskeletal injections for these problems in terms of medications, indications, injection technique, and supporting evidence from the literature. Experience with joint injection and the pharmacological principles described in this article should allow primary care physicians to become comfortable and proficient with musculoskeletal injections. PMID:19720781

  1. Enhanced tumor control with combination mTOR and PD-L1 inhibition in syngeneic oral cavity cancers

    PubMed Central

    Moore, Ellen C.; Cash, Harrison A.; Caruso, Andria M.; Uppaluri, Ravindra; Hodge, James W.; Van Waes, Carter; Allen, Clint T.

    2016-01-01

    Significant subsets of patients with oral cancer fail to respond to single-agent programmed death (PD) blockade. Syngeneic models of oral cancer were used to determine if blocking oncogenic signaling improved in vivo responses to PD-L1 monoclonal antibody (mAb). Anti-PD-L1 enhanced durable primary tumor control and survival when combined with mTOR (rapamycin), but not in combination with MEK inhibition (PD901) in immunogenic MOC1 tumors. Conversely, PD-L1 mAb did not enhance tumor control in poorly immunogenic MOC2 tumors. Rapamycin enhanced expansion of peripheral antigen-specific CD8 T cells and IFNγ production following ex vivo antigen stimulation. More CD8 T cells infiltrated and were activated after PD-L1 mAb treatment in mice with immunogenic MOC1 tumors, which was stable or increased by the addition of rapamycin, but suppressed when PD901 was added. Rapamycin increased IFNγ production capacity in peripheral and tumor-infiltrating CD8 T cells. In vivo antibody depletion revealed a CD8 T cell, and not NK cell, -dependent mechanism of tumor growth inhibition after treatment with rapamycin and PD-L1 mAb, ruling out significant effects from NK cell–mediated antibody-dependent cellular cytotoxicity. Rapamycin also enhanced IFNγ or PD-L1 mAb treatment–associated induction of MHC class I expression on MOC1 tumor cells, an effect abrogated by depleting infiltrating CD8 T cells from the tumor microenvironment. This data conflicts with traditional views of rapamycin as a universal immunosuppressant, and when combined with evidence of enhanced antitumor activity with the combination of rapamycin and PD-L1 mAb, suggests that this treatment combination deserves careful evaluation in the clinical setting. PMID:27076449

  2. Cellular Intrinsic Mechanism Affecting the Outcome of AML Treated with Ara-C in a Syngeneic Mouse Model

    PubMed Central

    Tan, Dongming; Su, Guangsong; Zheng, Yanwen; He, Chao; Mao, Zhengwei J.; Singleton, Timothy P.; Yin, Bin

    2014-01-01

    The mechanisms underlying acute myeloid leukemia (AML) treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. PMID:25314317

  3. Ovarian tumour growth is characterized by mevalonate pathway gene signature in an orthotopic, syngeneic model of epithelial ovarian cancer

    PubMed Central

    Greenaway, James B.; Virtanen, Carl; Osz, Kata; Revay, Tamas; Hardy, Daniel; Shepherd, Trevor; DiMattia, Gabriel; Petrik, Jim

    2016-01-01

    Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer and often is not detected until late stages when cancer cells transcoelomically metastasize to the abdomen and typically become resistant to therapy resulting in very low survival rates. We utilize an orthotopic, syngeneic mouse model to study late stage disease and have discovered that the tumor cells within the abdominal ascites are irreversibly re-programmed, with an increased tumorigenicity and resistance to apoptosis. The goal of this study was to characterize the reprogramming that occurred in the aggressive ascites-derived cells (28-2 cells) compared to the original cell line used for tumor induction (ID8 cells). Microarray experiments showed that the majority of genes upregulated in the 28-2 cells belonged to the mevalonate pathway, which is involved in cholesterol biosynthesis, protein prenylation, and activation of small GTPases. Upregulation of mevalonate appeared to be associated with the acquisition of a p53 mutation in the ascites-derived cells. Treatment with simvastatin to inhibit HMG CoA reductase, the rate limiting enzyme of this pathway, induced apoptosis in the 28-2 cell line. Rescue experiments revealed that mevalonate, but not cholesterol, could inhibit the simvastatin-mediated effects. In vivo, daily intraperitoneal simvastatin treatment significantly regressed advanced stage disease and induced death of metastatic tumor cells. These data suggest that ovarian cancer cells become reprogrammed, with genetic mutations, and upregulation of the mevalonate pathway, which facilitates the development of advanced stage disease. The use of statins to inhibit HMGCR may provide novel therapeutic opportunities for the treatment of advanced stage EOC. PMID:27329838

  4. Effects of cyclooxygenase-2 inhibitor and adenosine triphosphate-sensitive potassium channel opener in syngeneic mouse islet transplantation.

    PubMed

    Juang, J-H; Kuo, C-H

    2010-12-01

    In the initial days after transplantation, islet grafts may be attacked by cytokines via cyclooxygenase-2 (COX-2), producing primary nonfunction. In addition, chronic overstimulation of β-cells may impair insulin secretion. To enhance the function of transplanted islets, the present study investigated the effects of rofecoxib, a COX-2 inhibitor, and NN414 (6-chloro-3-[1-methylcyclopropyl]amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide), an adenosine triphosphate-sensitive potassium channel opener, on islet transplantation. Male inbred C57BL/6 mice were used as donors and recipients. One hundred fifty islets were isolated via collagenase digestion and density gradient, and syngeneically transplanted under the kidney capsule in mice with streptozotocin-induced diabetes. Recipients were treated with or without rofecoxib, 10 mg/kg/d orally, or with or without NN414, 3 mg/kg/d orally, for 4 weeks. After transplantation, recipient body weight, blood glucose concentration, and intraperitoneal glucose tolerance were measured. The grafted kidney was extracted for determination of insulin content at 4 weeks. In the rofecoxib-treated and NN414-treated groups and both control groups, body weight remained stable, and the blood glucose concentration decreased progressively. However, at 4 weeks after transplantation in the groups treated or not treated with rofecoxib or NN414, no significant difference was observed in recipient body weight, blood glucose concentration, and glucose tolerance or in insulin content of the graft. These data indicate that posttransplantation treatment with rofecoxib or NN414 has no beneficial effect on transplantation outcome in diabetic mouse recipients engrafted with a marginal islet mass.

  5. Behavioral evidence of thermal hyperalgesia and mechanical allodynia induced by intradermal cinnamaldehyde in rats

    PubMed Central

    Tsagareli, Merab G.; Tsiklauri, Nana; Zanotto, Karen L.; Carstens, Mirela Iodi; Klein, Amanda H.; Sawyer, Carolyn M.; Gurtskaia, Gulnazi; Abzianidze, Elene; Carstens, E.

    2010-01-01

    TRPA1 agonists cinnamaldehyde (CA) and mustard oil (allyl isothiocyanate= AITC) induce heat hyperalgesia and mechanical allodynia in human skin, and sensitize responses of spinal and trigeminal dorsal horn neurons to noxious skin heating in rats. TRPA1 is also implicated in cold nociception. We presently used behavioral methods to investigate if CA affects sensitivity to thermal and mechanical stimuli in rats. Unilateral intraplantar injection of CA (5-20%) induced a significant, concentration-dependent reduction in latency for ipsilateral paw withdrawal from a noxious heat stimulus, peaking (61.7% of pre-injection baseline) by 30 min with partial recovery at 120 min. The highest dose of CA also significantly reduced the contralateral paw withdrawal latency. CA significantly reduced mechanical withdrawal thresholds of the injected paw that peaked sooner (3 min) and was more profound (44.4% of baseline), with no effect contralaterally. Bilateral intraplantar injections of CA resulted in a significant cold hyperalgesia (cold-plate test) and a weak enhancement of innocuous cold avoidance (thermal preference test). The data are consistent with roles for TRPA1 in thermal (hot and cold) hyperalgesia and mechanical allodynia. PMID:20219630

  6. Abaloparatide Injection

    MedlinePlus

    ... of a natural human hormone called parathyroid hormone (PTH). It works by causing the body to build ... container.You should know that abaloparatide injection may cause dizziness, lightheadedness, and fainting when you get up ...

  7. Sumatriptan Injection

    MedlinePlus

    ... accompanied by nausea and sensitivity to sound and light). Sumatriptan injection is also used to treat the ... children. Store it at room temperature, away from light, excess heat, and moisture (not in the bathroom). ...

  8. Certolizumab Injection

    MedlinePlus

    ... has not improved when treated with other medications, rheumatoid arthritis (a condition in which the body attacks its ... continues. When certolizumab injection is used to treat rheumatoid arthritis, it is usually given every other week and ...

  9. Acyclovir Injection

    MedlinePlus

    ... chickenpox in the past) in people with weak immune systems. It is also used to treat first-time ... from time to time) in people with normal immune systems. Acyclovir injection is used to treat herpes simplex ...

  10. Doxercalciferol Injection

    MedlinePlus

    Doxercalciferol injection is used to treat secondary hyperparathyroidism (a condition in which the body produces too much parathyroid hormone [PTH; a natural substance needed to control the amount of calcium in ...

  11. Evolocumab Injection

    MedlinePlus

    ... how to inject this medication.Remove the prefilled syringe or prefilled autoinjector from the refrigerator and allow it to ... before using it. Do not warm the prefilled syringe or prefilled autoinjector in hot water, microwave, or place in ...

  12. Ixekizumab Injection

    MedlinePlus

    ... as a as a solution (liquid) in a prefilled syringe, and as a prefilled autoinjector to inject subcutaneously ( ... dispose of the puncture-resistant container.Remove the prefilled syringe or autoinjector from the refrigerator. Place it on ...

  13. Alirocumab Injection

    MedlinePlus

    ... how to inject this medication.Remove the prefilled syringe or prefilled dosing pen from the refrigerator and allow it ... hours or longer. Do not put the prefilled syringe or prefilled dosing pen back in the refrigerator after it ...

  14. Daclizumab Injection

    MedlinePlus

    Daclizumab comes as a solution (liquid) in a prefilled syringe to inject subcutaneously (under the skin). It is ... or tattooed.Never reuse or share needles or prefilled syringes of medication. Throw away used syringes in a ...

  15. Sarilumab Injection

    MedlinePlus

    ... receive any vaccines. You should not receive any vaccinations while you are using sarilumab injection without talking ... pregnant, tellyour doctor before the baby receives any vaccinations.if you are having surgery, including dental surgery, ...

  16. Zidovudine Injection

    MedlinePlus

    ... zidovudine injection does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) ... sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus ...

  17. Rasburicase Injection

    MedlinePlus

    ... as tumors break down) in people with certain types of cancer who are being treated with chemotherapy medications. Rasburicase injection is in a class of medications called enzymes. It works by breaking down uric acid so ...

  18. Haloperidol Injection

    MedlinePlus

    ... release injection are used to treat schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of ... medications); medications for anxiety, depression, irritable bowel disease, mental illness, motion sickness, Parkinson's disease, seizures, ulcers, or urinary ...

  19. Risperidone Injection

    MedlinePlus

    ... acting) injection is used to treat schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of ... ropinirole (Requip); medications for anxiety, blood pressure, or mental illness; medications for seizures such as carbamazepine (Carbatrol, Epitol, ...

  20. Thiotepa Injection

    MedlinePlus

    ... that begins in the female reproductive organs where eggs are formed), breast, and bladder cancer. It is ... comes as a powder to be mixed with liquid to be injected intravenously (into a vein) by ...

  1. Methotrexate Injection

    MedlinePlus

    ... Methotrexate injection is also used to treat severe psoriasis (a skin disease in which red, scaly patches ... slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells to ...

  2. Cefazolin Injection

    MedlinePlus

    ... is used to treat certain infections caused by bacteria including skin, bone, joint, genital, blood, heart valve, ... medications called cephalosporin antibiotics. It works by killing bacteria.Antibiotics such as cefazolin injection will not work ...

  3. Trastuzumab Injection

    MedlinePlus

    ... completed for up to 52 weeks. When trastuzumab injection is used to treat stomach cancer, it is usually given once every 3 weeks. The length of your treatment depends on how well your body responds to the medication and the ...

  4. Bendamustine Injection

    MedlinePlus

    ... leukemia (CLL; a type of cancer of the white blood cells). Bendamustine injection is also used to treat a ... NHL: cancer that begins in a type of white blood cell that normally fights infection) that is slow spreading, ...

  5. Palonosetron Injection

    MedlinePlus

    ... that may occur several days after receiving certain chemotherapy medications. Palonosetron injection is in a class of medications called 5-HT3 receptor antagonists. It works by blocking the action of serotonin, a natural ...

  6. Doxycycline Injection

    MedlinePlus

    ... injection is in a class of medications called tetracycline antibiotics. It works by killing bacteria that cause ... are allergic to doxycycline, minocycline (Dynacin, Minocin, Solodyn), tetracycline (Achromycin V), any other medications, or any of ...

  7. Dexamethasone Injection

    MedlinePlus

    ... severe allergic reactions. It is used in the management of certain types of edema (fluid retention and ... needed for normal body functioning) and in the management of certain types of shock. Dexamethasone injection is ...

  8. Levofloxacin Injection

    MedlinePlus

    ... infections. Levofloxacin injection is also used to prevent anthrax (a serious infection that may be spread on ... in people who may have been exposed to anthrax germs in the air and treat and prevent ...

  9. Omalizumab Injection

    MedlinePlus

    ... steroids. Omalizumab is also used to treat chronic hives without a known cause that cannot successfully be ... is not used to treat other forms of hives or allergic conditions. Omalizumab injection is in a ...

  10. Plerixafor Injection

    MedlinePlus

    ... used along with a granulocyte-colony stimulating factor (G-CSF) medication such as filgrastim (Neupogen) or pegfilgrastim ( ... injection will begin after you have received a G-CSF medication once a day for 4 days, ...

  11. Avelumab Injection

    MedlinePlus

    ... doctor or nurse in a medical facility or infusion center. It is usually given once every 2 ... Avelumab injection may cause serious reactions during the infusion of the medication. You may be given other ...

  12. Alemtuzumab Injection

    MedlinePlus

    ... injection, the medication is usually given three times weekly on alternate days (usually Monday, Wednesday, and Friday) ... that you eat foods that are rich in iron such as meats, leafy green vegetables, and fortified ...

  13. Dinutuximab Injection

    MedlinePlus

    ... treat neuroblastoma (a cancer that begins in nerve cells) in children who have responded to other treatments. Dinutuximab injection is in a class of medications called monoclonal antibodies. It works by killing cancer cells.

  14. Cyclosporine Injection

    MedlinePlus

    ... transplanted organ by the immune system of the person receiving the organ) in people who have received kidney, liver, and heart transplants. Cyclosporine injection should only be used to treat people who are unable to take cyclosporine by mouth. ...

  15. Denosumab Injection

    MedlinePlus

    ... menstrual periods), who have an increased risk for fractures (broken bones) or who cannot take or did ... receiving certain treatments that increase their risk for fractures. Denosumab injection (Xgeva) is used to reduce fractures ...

  16. Epinephrine Injection

    MedlinePlus

    ... emergency medical treatment to treat life-threatening allergic reactions caused by insect bites or stings, foods, medications, ... at the first sign of a serious allergic reaction. Use epinephrine injection exactly as directed; do not ...

  17. Aflibercept Injection

    MedlinePlus

    ... injection is used to treat wet age-related macular degeneration (AMD; an ongoing disease of the eye that ... that leads to blurry vision and vision loss), diabetic macular edema (an eye disease caused by diabetes that can ...

  18. Fondaparinux Injection

    MedlinePlus

    ... the leg), which can lead to pulmonary embolism (PE; a blood clot in the lung), in people ... with warfarin (Coumadin, Jantoven) to treat DVT or PE. Fondaparinux injection is in a class of medications ...

  19. Panitumumab Injection

    MedlinePlus

    ... as a solution (liquid) to be given by infusion (injected into a vein). It is usually given ... doctor or nurse in a doctor's office or infusion center. Panitumumab is usually given once every 2 ...

  20. Topotecan Injection

    MedlinePlus

    ... organs where eggs are formed) and small cell lung cancer (a type of cancer that begins in the ... topotecan injection is used to treat ovarian or lung cancer, it is usually given once a day for ...

  1. Gemcitabine Injection

    MedlinePlus

    ... with surgery. Gemcitabine is also used to treat cancer of the pancreas that has spread to other parts of the ... 4 weeks. When gemcitabine is used to treat cancer of pancreas it may be injected once every week. The ...

  2. Lacosamide Injection

    MedlinePlus

    ... with other medications to control certain types of seizures in people who cannot take oral medications. Lacosamide ... If you suddenly stop using lacosamide injection, your seizures may happen more often. Your doctor will probably ...

  3. Pegloticase Injection

    MedlinePlus

    ... doctor if you have glucose-6-phosphate dehydrogenase (G6PD) deficiency (an inherited blood disease). Your doctor may test you for G6PD deficiency before you start to receive pegloticase injection. If ...

  4. Ibritumomab Injection

    MedlinePlus

    ... is in a class of medications called monoclonal antibodies with radioisotopes. It works by attaching to cancer ... you receive ibritumomab injection, your body may develop antibodies (substances in the blood that help the immune ...

  5. Oxytocin Injection

    MedlinePlus

    Oxytocin injection is used to begin or improve contractions during labor. Oxytocin also is used to reduce bleeding after childbirth. ... other medications or procedures to end a pregnancy. Oxytocin is in a class of medications called oxytocic ...

  6. Edaravone Injection

    MedlinePlus

    Edaravone injection is used to treat amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease; a condition in which the nerves that control muscle movement slowly die, causing the muscles to shrink and ...

  7. Pentamidine Injection

    MedlinePlus

    Pentamidine injection is used to treat pneumonia caused by a fungus called Pneumocystis carinii. It is in a class of medications called antiprotozoals. It works by stopping the growth of protozoa that can cause pneumonia.

  8. Diphenhydramine Injection

    MedlinePlus

    ... or along with other medications to control abnormal movements in people who have Parkinsonian syndrome (a disorder of the nervous system that causes difficulties with movement, muscle control, and balance). Diphenhydramine injection should not ...

  9. Docetaxel Injection

    MedlinePlus

    ... allergic to docetaxel injection or drugs made with polysorbate 80, an ingredient found in some medications. Ask ... if a medication you are allergic to contains polysorbate 80. If you experience any of the following ...

  10. Octreotide Injection

    MedlinePlus

    ... hormone (a natural substance) produced by people with acromegaly (condition in which the body produces too much ... Octreotide long-acting injection is used to control acromegaly, carcinoid tumors, and VIP-omas in people who ...

  11. Vedolizumab Injection

    MedlinePlus

    ... injection may cause serious allergic reactions during an infusion and for several hours afterward. A doctor or ... of the following symptoms during or after your infusion: rash; itching; swelling of the face, eyes, mouth, ...

  12. Granisetron Injection

    MedlinePlus

    ... that may occur after surgery. Granisetron extended-release (long-acting) injection is used with other medications to prevent nausea and vomiting caused by cancer chemotherapy that may occur immediately ...

  13. Fluconazole Injection

    MedlinePlus

    ... injection is used to treat fungal infections, including yeast infections of the mouth, throat, esophagus (tube leading ... by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become ...

  14. Intravitreal injection

    MedlinePlus

    ... You may have this procedure if you have: Macular degeneration : An eye disorder that slowly destroys sharp, central ... injection References American Academy of Ophthalmology. Age-related macular degeneration PPP - updated 2015. Aao.org web site. Updated ...

  15. Ciprofloxacin Injection

    MedlinePlus

    ... is used to treat certain infections caused by bacteria such as pneumonia; and infections of the skin, ... of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections.Antibiotics such as ciprofloxacin injection ...

  16. Tobramycin Injection

    MedlinePlus

    ... treat certain serious infections that are caused by bacteria such as meningitis (infection of the membranes that ... medications called aminoglycoside antibiotics. It works by killing bacteria.Antibiotics such as tobramycin injection will not work ...

  17. Ceftriaxone Injection

    MedlinePlus

    ... is used to treat certain infections caused by bacteria such as gonorrhea (a sexually transmitted disease), pelvic ... medications called cephalosporin antibiotics. It works by killing bacteria.Antibiotics such as ceftriaxone injection will not work ...

  18. Moxifloxacin Injection

    MedlinePlus

    ... is used to treat certain infections caused by bacteria such as pneumonia; ; and , skin, and abdominal (stomach ... antibiotics called fluoroquinolones. It works by killing the bacteria that cause infections.Antibiotics such as moxifloxacin injection ...

  19. Daptomycin Injection

    MedlinePlus

    ... in adults or serious skin infections caused by bacteria in adults and children 1 year of age ... called cyclic lipopeptide antibiotics. It works by killing bacteria.Antibiotics such as daptomycin injection will not work ...

  20. Amikacin Injection

    MedlinePlus

    ... treat certain serious infections that are caused by bacteria such as meningitis (infection of the membranes that ... medications called aminoglycoside antibiotics. It works by killing bacteria.Antibiotics such as amikacin injection will not work ...

  1. Meropenem Injection

    MedlinePlus

    ... skin and abdominal (stomach area) infections caused by bacteria and meningitis (infection of the membranes that surround ... of medications called antibiotics. It works by killing bacteria that cause infection.Antibiotics such as meropenem injection ...

  2. Cefepime Injection

    MedlinePlus

    ... is used to treat certain infections caused by bacteria including pneumonia, and skin, urinary tract, and kidney ... medications called cephalosporin antibiotics. It works by killing bacteria.Antibiotics such as cefepime injection will not work ...

  3. Ertapenem Injection

    MedlinePlus

    ... abdominal (stomach area) infections, that are caused by bacteria. It is also used for the prevention of ... medications called carbapenem antibiotics. It works by killing bacteria.Antibiotics such as ertapenem injection will not work ...

  4. Aztreonam Injection

    MedlinePlus

    ... to treat certain infections that are caused by bacteria, including respiratory tract (including pneumonia and bronchitis), urinary ... abdominal (stomach area) infections, that are caused by bacteria. Aztreonam injection also may be used before, during, ...

  5. Ceftaroline Injection

    MedlinePlus

    ... infections and pneumonia (lung infection) caused by certain bacteria. Ceftaroline is in a class of medications called cephalosporin antibiotics. It works by killing bacteria.Antibiotics such as ceftaroline injection will not work ...

  6. Cefotaxime Injection

    MedlinePlus

    ... is used to treat certain infections caused by bacteria including pneumonia and other lower respiratory tract (lung) ... medications called cephalosporin antibiotics. It works by killing bacteria.Antibiotics such as cefotaxime injection will not work ...

  7. Cefuroxime Injection

    MedlinePlus

    ... is used to treat certain infections caused by bacteria including pneumonia and other lower respiratory tract (lung) ... medications called cephalosporin antibiotics. It works by killing bacteria.Antibiotics such as cefuroxime injection will not work ...

  8. Ampicillin Injection

    MedlinePlus

    ... to treat certain infections that are caused by bacteria such as meningitis (infection of the membranes that ... of medications called penicillins. It works by killing bacteria.Antibiotics such as ampicillin injection will not work ...

  9. Gentamicin Injection

    MedlinePlus

    ... treat certain serious infections that are caused by bacteria such as meningitis (infection of the membranes that ... medications called aminoglycoside antibiotics. It works by killing bacteria.Antibiotics such as gentamicin injection will not work ...

  10. MEDICAL INJECTION

    NASA Image and Video Library

    1963-06-10

    S62-08371 (1962) --- The automatic medical injectors carried on the Mercury-Atlas 9 flight. The injectors provide the astronaut with injection tubes of Tigan, for preventing motion sickness and Demerol, for relieving pain. The tubes encased in the block are stowed in the astronauts survival kit. The single injection tubes are placed in a pocket of the astronauts spacesuit. Photo credit: NASA

  11. Injection overview

    SciTech Connect

    Prestwich, S.

    1983-12-01

    The test program was initiated at the Raft River Geothermal Field in southern Idaho in September 1982. A series of eight short-term injection and backflow tests, followed by a long-term injection test, were conducted on one well in the field. Tracers were added during injection and monitored during backflow as well. The principal objective was to determine if tracers could be effectively used as a means to assess reservoir characteristics in a one-well test. The test program resulted in a unique data set which shows promise as a means to improve understanding of the reservoir characteristics. In December 1982, an RFP was issued to obtain an industrial partner to obtain follow-on data on the injection/backflow technique in a second field, and to study any alternate advanced concepts for injection testing which the industrial community might recommend. The East Mesa Geothermal Field was selected for the second test series. Two wells were utilized for testing, and a series of ten tests were conducted in July and August 1983, aimed principally at further evaluation of the injection/backflow technique.

  12. Local reaction secondary to insulin injection. A potential role for latex antigens in insulin vials and syringes.

    PubMed

    Towse, A; O'Brien, M; Twarog, F J; Braimon, J; Moses, A C

    1995-08-01

    To evaluate the possibility that latex antigens (natural rubber) can contribute to or cause local sensitivity at insulin injection sites. A subject with documented local cutaneous allergic reactions at the site of insulin injections and with systemic latex allergy manifested as anaphylaxis was tested with intradermal injections of insulin diluent from two manufacturers and with two brands of insulin syringes. The subject had high titer anti-latex Ige and elevated total levels of IgE in serum. Anti-insulin IgG and IgE antibodies were absent. Erythema and wheals occurred at the sites of intradermal injection of insulin therapy components (insulin diluent and syringes) that contain natural latex rubber but not at the site of injection of insulin therapy components that do not contain natural latex rubber. Small quantities of natural latex rubber antigens in insulin injection materials can be sufficient to produce local cutaneous reactions at the site of insulin injection in individuals highly allergic to natural latex rubber.

  13. Description of Riouxgolvania kapapkamui Sp. N. (Nematoda: Muspiceoidea: Muspiceidae), a peculiar intradermal parasite of bats in Hokkaido, Japan.

    PubMed

    Hasegawa, Hideo; Satô, Masahiko; Maeda, Kishio; Murayama, Yoshiko

    2012-10-01

    Riouxgolvania kapapkamui sp. n. (Nematoda: Muspiceoidea: Muspiceidae), a peculiar intradermal parasite, is described based on gravid adults, eggs, and first-, second-, and third-stage larvae collected from dermal nodules formed in Myotis macrodactylus and Myotis ikonnikovi bats from Hokkaido, Japan. The nematode is readily distinguished from 3 previously described congeners in having a globular body with brown, transverse striae in the anterior region of fully grown females. The third-stage larva is also distinguished from other congeners by having a round tail end. Nucleotide sequences of the analyzed partial SSU rDNA-ITS1 region and partial cytochrome c oxidase subunit 1 of mtDNA showed greater similarity to chromadoreans rather than to enopleans. This is the first report of muspiceoid nematodes from Asia.

  14. Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.

    PubMed

    Yoon, S-Y; Park, S Y; Kim, S; Lee, T; Lee, Y S; Kwon, H-S; Cho, Y S; Moon, H-B; Kim, T-B

    2013-07-01

    Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Interpretation Criteria for Comparative Intradermal Tuberculin Test for Diagnosis of Bovine Tuberculosis in Cattle in Maroua Area of Cameroon

    PubMed Central

    Temwa, J.; Mouiche, M. M.; Iyawa, D.; Zoli, P. A.

    2016-01-01

    Intradermal tuberculin test (TST) is the choice method for diagnosis of bovine tuberculosis (Tb) in live animals. This work was done to assess the performance of single intradermal comparative cervical tuberculin (SICCT) test in randomly selected cattle in Maroua, Cameroon, against detection of Tb lesions and detection of Tb lesions plus acid fast bacilli in lesions. While 22.28% of slaughtered cattle presented Tb lesions at meat inspection, detection rates of anti-bovine-Tb antibody, Tb lesions, and Tb lesions plus acid fast bacilli were 68.57%, 32.95%, and 22.35%, respectively. SICCT-bovine-Tb positive cattle were 35.29%, 29.41%, 25.88%, 24.7%, and 21.18% at ≥2 mm, ≥2.5 mm, ≥3 mm, ≥3.5 mm, and ≥4 mm cut-offs, respectively. Higher sensitivity and predictive values were obtained at severe interpretations. The best performance was at ≥3 mm and ≥3.5 mm cut-offs. Against detection of Tb lesions, ≥3 mm and ≥3.5 mm showed sensitivity of 67.8% and specificity of 94.7% and 96.5%, respectively. For detection of Tb lesions accompanied with acid fast bacilli in lesions, ≥3 mm and ≥3.5 mm showed sensitivity of 89.4% and specificity of 92.4% and 93.9%, respectively. These findings revealed that interpretations of SICCT-bovine-Tb should be at ≥3 mm and/or ≥3.5 mm cut-offs. Severe interpretation of TST is essential for optimal diagnosis of bovine Tb in cattle in Maroua, Cameroon. PMID:27563481

  16. Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles.

    PubMed

    Elnehrawy, Naema Y; Ibrahim, Zeinab A; Eltoukhy, Azza M; Nagy, Hala M

    2017-03-01

    Platelet-rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration. To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation. A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale. The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability. Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs. © 2016 Wiley Periodicals, Inc.

  17. Immunogenicity and safety of Fluzone(®) intradermal and high-dose influenza vaccines in older adults ≥65 years of age: a randomized, controlled, phase II trial.

    PubMed

    Tsang, Peter; Gorse, Geoffrey J; Strout, Cynthia B; Sperling, Malcolm; Greenberg, David P; Ozol-Godfrey, Ayca; DiazGranados, Carlos; Landolfi, Victoria

    2014-05-01

    We conducted a randomized, controlled, multicenter, phase II study to evaluate the immunogenicity and safety of an investigational intradermal (ID) trivalent influenza vaccine (TIV) and a high-dose (HD) intramuscular (IM) TIV in older adults (≥65 years of age). Older adult subjects were immunized with ID vaccine containing either 15μg hemagglutinin (HA)/strain (n=636) or 21μg HA/strain (n=634), with HD IM vaccine containing 60μg HA/strain (n=320), or with standard-dose (SD) IM vaccine (Fluzone(®); 15μg HA/strain; n=319). For comparison, younger adults (18-49 years of age) were immunized with SD IM vaccine. In older adults, post-vaccination geometric mean titers induced by the ID vaccines were superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains and non-inferior for the B strain. Seroconversion rates induced by the ID vaccines were superior to those induced by the SD IM vaccine in older adults for the A/H1N1 and B strains and non-inferior for the A/H3N2 strain. Results did not differ significantly for the two ID vaccine dosages. Post-vaccination geometric mean titers, seroconversion rates, and most seroprotection rates were significantly higher in HD vaccine recipients than in older adult recipients of the SD IM or ID vaccines and, for most measures, were comparable to those of younger adult SD IM vaccine recipients. Injection-site reactions, but not systemic reactions or unsolicited adverse events, were more common with the ID vaccines than with the IM vaccines. No treatment-related serious adverse events were reported. This study demonstrated that: (1) the ID and HD vaccines were well-tolerated and more immunogenic than the SD IM vaccine in older adults; (2) the HD vaccine was more immunogenic than the ID vaccines in older adults; and (3) the HD vaccine in older adults and the SD IM vaccine in younger adults elicited comparable antibody responses (ClinicalTrials.gov identifier no.: NCT00551031).

  18. Red Ginseng Administration Before Islet Isolation Attenuates Apoptosis and Improves Islet Function and Transplant Outcome in a Syngeneic Mouse Marginal Islet Mass Model.

    PubMed

    Kim, J S; Jang, H J; Kim, S S; Oh, M Y; Kim, H J; Lee, S Y; Eom, D W; Ham, J Y; Han, D J

    2016-05-01

    Transplantation of isolated islets is a promising treatment for diabetes. Red ginseng (RG) is steamed ginseng and has been reported to enhance insulin secretion-stimulating and anti-apoptotic activities in pancreatic β-cells. In this study, we examined the hypothesis that pre-operative RG treatment enhances islet cell function and anti-apoptosis and investigated whether RG improves islet engraftment by transplant of a marginal mass of syngeneic islets pretreated with RG in diabetic mice. Balb/c mice were randomly divided into 2 groups, and 1 group was administered RG (400 mg/kg/day orally) for 7 days before islet isolation. In vitro islet viability and function were assessed. After cytokine treatment, cell viability, function, and apoptosis of islet cells were analyzed. Furthermore, we studied the effects of RG in a syngeneic islet graft model. A marginal mass of syngeneic mouse islets was transplanted into diabetic hosts. Islet pretreatment with RG showed 1.4-fold higher glucose-induced insulin secretion than did control islets. RG pretreatment upregulated B-cell lymphoma 2 (Bcl-2) expression and downregulated Bcl-associated X protein (BAX), caspase-3, and inducible nitric oxide synthase (iNOS) expression. Glucose-induced insulin release, NO, and apoptosis were significantly improved in RG-pretreated islets compared with cytokine-treated islets. RG-pretreated mice exhibited improved marginal mass islet graft survival compared with controls. These results suggest that pre-operative RG administration enhanced islet function before transplantation and attenuated cytokine-induced damage associated with apoptosis. These studies indicate that inhibition of apoptosis by RG significantly improved islet cell and graft function after isolation and transplantation, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. [The comparative pathomorphological evaluation of the mice-recipient's brain cell-tissue reactions by the intracerebral imlantation of syngeneic and allogeneic neural cells].

    PubMed

    Liubych, L D; Semenova, V M; Lisianyĭ, M I

    2013-01-01

    The aim of the study was to compare the mice-recipient's brain tissue cell-structural reactions in response to intracerebral implantation of syngeneic and allogeneic cell suspensions of neural progenitor cells (NPC) (E13-15). The NPC suspensions from mice-donors of C57BL/6 and CBA containing 72.7 +/- 9.9% Vimentin+ and 81, 812, 5% GFAP+ cells were inoculated by standard procedure in right temporal segment of cerebral hemisphere of mice-recipients C57BL/6 (1 x 10(6) cells per animal). The certain part of mice-recipients of allogeneic NPC were immunosupressed by Sandimmune (100 mkg per animal) on day 0, 3, 6 after neurotransplantation. The standard histological preparations of mice brains were performed after 24 hours, 6, 12, 18 and 37 days after NPC neurotransplantation, which were investigated by cytoanalyzer "IBAS" (Germany). After intracerebral inoculation of allogeneic foetal NPC the signs of the pericellular edema and lymphocyte infiltration were detected in adjacent brain sections on day 12-18 and decreased on day 37. Allogeneic foetal NPC were reserved till day 18 and revealed the signs of primary differentiation. After immunosupression by "Sandimmune" the foetal NPC underwent the phoenotypic differentiation and infiltration in related brain sections. On the day 37 the implanted NPC were not detected. Focal reaction of the brain glial component to implanted NPC declined faster after syngeneic NPC neuroimplantation (up to day 18) than after allogeneic NPC neuroimplantation (up to day 37). After the syngeneic NPC inoculation on the 37th day at the site of implantation the formation of a small fragment of immature bone was fixed, which may indicate the possibility of NPC transdifferentiation in other cell types.

  20. Antigen receptors on murine T lymphocytes in contact sensitivity. II. Presentation and characterization of syngeneic anti-idiotype serum against DNFB-sensitized T cells.

    PubMed

    Moorhead, J W; Sy, M S

    1982-06-01

    This manuscript describes the preparation and characterization of a syngeneic antiserum raised in BALB/c mice against nylon wool-purified lymph node (LN) T cells from 2,4-dinitrofluorobenzene- (DNFB) sensitized BALB/c mice. This antiserum (anti-T DH-DNP) plus complement blocks the ability of LN or purified T cells from DNFB-sensitized donors to transfer immunity to naive recipients. The inhibitory activity of the serum is due to antibodies; these antibodies have specificity for idiotype (Id) determinants as shown by their ability to bind to purified mouse anti-DNP antibodies but not to rabbit anti-DNP or normal mouse Ig. Inhibition of transfer of immunity by the anti-Id serum is not restricted by either H-2 gene products or Igh-1 allotypes. The antiserum is antigen specific when tested on LN cells from oxazolone-sensitized mice, but has a low level of cross-reactivity against T cells from 2,4,6-trinitrochlorobenzene- (TNCB) sensitized mice. In addition, it was shown that naturally occurring anti-Id antibodies, epsilon-DNP-L-lysine, or DNP-protein (but not NIP-protein) and the anti-Id in syngeneic anti-T DH-DNP serum compete for similar binding sites on DNFB-immune T cells. We interpret these findings to indicate that immunization of mice with T cells from DNFB-sensitized syngeneic mice induces the production of anti-Id antibodies. These anti-Id antibodies are specific for determinants expressed on the T cell receptor or receptor subsite that is specific for the hapten DNP.

  1. Cytotoxic T lymphocytes induced against allogeneic I-region determinants react with Ia molecules on trinitrophenyl-conjugated syngeneic target cells.

    PubMed

    Billings, P; Burakoff, S; Dorf, M E; Benacerraf, B

    1977-08-01

    The major histocompatibility complex codes for determinants which are recognized by and serve as targets for cytolytic T lymphocytes (CTL) (1). Antigens coded for by the K and D loci of the H-2 complex can activate xenogeneic or allogeneic CTL (2,3). In addition, the H-2K or H-2D gene products function as those molecules against which syngeneic CTL responses specific for chemical, viral, and minor H antigens are directed (4-8). It has recently been shown that Ia determinants can also serve as target antigens for distinct but weaker CTL responses (9-13). Those clones which recognize Ia antigens see them independently of K- or D- coded antigens as shown in genetic studies and by antisera-blocking experiments (12,13). We have proposed that the existence of clones of CTL specific for I-region-coded determinants is not fortuitous; rather these clones specifically recognize Ia determinants and may have an immunoregulatory role. These CTL may affect those immune functions which are at least partially dependent on or controlled by I-region-coded molecules. Two predictions can be made and tested concerning the role of Ia determinants in cytolytic systems and the role, if any, of I-region- specific CTL in regulating the immune response: (a) that if as we and others have shown, certain Ia specificities can serve as a third series of major histocompatibility antigens, then Ia antigens should be susceptible to the same types of antigenic modifications as H-2K- or H-2D-coded structures and thus serve as targets for CTL directed against modified-self in selected systems; and (b) that allogeneically induced I-region-specific CTL should demonstrate cross-reactivity with targets bearing modified syngeneic I-region-coded determinants. Data will be present which demonstrates that trinitrophenyl (TNP)-modified syngeneic I-region determinants can serve as targets for CTL induced by allogeneic Ia antigens.

  2. Adverse effect on syngeneic islet transplantation by transgenic coexpression of decoy receptor 3 and heme oxygenase-1 in the islet of NOD mice.

    PubMed

    Huang, S-H; Lin, G-J; Chien, M-W; Chu, C-H; Yu, J-C; Chen, T-W; Hueng, D-Y; Liu, Y-L; Sytwu, H-K

    2013-03-01

    Decoy receptor 3 (DcR3) blocks both Fas ligand- and LIGHT-induced pancreatic β-cell damage in autoimmune diabetes. Heme oxygenase 1 (HO-1) possesses antiapoptotic, anti-inflammatory, and antioxidative effects that protect cells against various forms of attack by the immune system. Previously, we have demonstrated that transgenic islets overexpressing DcR3 or murine HO-1 (mHO-1) exhibit longer survival times than nontransgenic islets in syngeneic islet transplantation. In this study, we evaluated whether DcR3 and mHO-1 double-transgenic islets of NOD mice could provide better protective effects and achieve longer islet graft survival than DcR3 or mHO-1 single-transgenic islets after islet transplantation. We generated DcR3 and mHO-1 double-transgenic NOD mice that specifically overexpress DcR3 and HO-1 in islets. Seven hundred islets isolated from double-transgenic, single-transgenic, or nontransgenic NOD mice were syngeneically transplanted into the kidney capsules of newly diabetic female recipients. Unexpectedly, there was no significant difference in the survival time between double-transgenic or nontransgenic NOD islet grafts, and the survival times of double-transgenic NOD islet grafts were even shorter than those of DcR3 or mHO-1 single-transgenic islets. Our data indicate that transplantation of double-transgenic islets that coexpress HO-1 and DcR3 did not result in a better outcome. On the contrary, this strategy even caused an adverse effect in syngeneic islet transplantation.

  3. XIAP inhibition of β-cell apoptosis reduces the number of islets required to restore euglycemia in a syngeneic islet transplantation model.

    PubMed

    Plesner, Annette; Soukhatcheva, Galina; Korneluk, Robert G; Verchere, C Bruce

    2010-01-01

    Clinical pancreatic islet transplantation has great promise as a treatment for type 1 diabetes but despite recent advances, it is still limited by the need for lifelong immunosuppression, restricted availability of donor islets, and uncertainty regarding long-term graft survival. Using a syngeneic, suboptimal islet transplantation model, we asked whether adenoviral overexpression of an anti-apoptotic protein, the X-linked inhibitor of apoptosis protein (XIAP) would protect transplanted islet cells from death and reduce the number of islets required for successful transplantation. Transplantation of 100 XIAP-expressing islets into the kidney capsule of syngeneic Balb/c mice restored euglycemia in 86% of recipients, where transplantation of 100 islets transduced with a control adenovirus expressing LacZ restored euglycemia in only 27% of recipients. Analysis of islet grafts by insulin/TUNEL double immunostaining revealed fewer apoptotic beta-cells in recipients of XIAP- compared with LacZ-expressing grafts (0.8±0.5 vs. 2.4±0.8 double-positive cells/graft), suggesting that XIAP enhances graft success by inhibiting β-cell apoptosis in the immediate post-transplant period. In summary, XIAP overexpression inhibits beta cell apoptosis in syngeneic islet transplants, thereby reducing the number of islets and decreasing the number of days required to restore euglycemia. These data raise the possibility that ex vivo XIAP gene transfer in islets prior to transplantation has the potential to increase the number of donor islets available for transplantation and may enhance graft function and long-term transplant success.

  4. Ganciclovir Injection

    MedlinePlus

    ... tests to check your body's response to ganciclovir injection.It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or ...

  5. Pertuzumab Injection

    MedlinePlus

    ... tests to check your body's response to pertuzumab injection.It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or ...

  6. Mitoxantrone Injection

    MedlinePlus

    ... to the treatment.If you are using mitoxantrone injection for MS, you should know that it controls MS but does not cure it. Continue to receive treatments even if you feel well. Talk to your doctor if you no longer ...

  7. Olaratumab Injection

    MedlinePlus

    ... your pharmacist any questions you have about olaratumab injection.It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or ...

  8. Reslizumab Injection

    MedlinePlus

    ... the infusion or for a short period of time after the infusion has finished.You will receive each injection of reslizumab in a doctor's office or medical facility. You will stay in the office for some time after you receive the medication so your doctor ...

  9. Teduglutide Injection

    MedlinePlus

    ... syndrome in people who need additional nutrition or fluids from intravenous (IV) therapy. Teduglutide injection is in a class of medications called glucagon-like peptide-2 (GLP-2) analogs. It works by improving the absorption of fluids and nutrients in the intestines.

  10. Pegaptanib Injection

    MedlinePlus

    ... if you have or have ever had diabetes, high blood pressure, a heart attack, or a stroke.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using pegaptanib injection, ...

  11. Differential effect of allogeneic versus syngeneic mesenchymal stem cell transplantation in MRL/lpr and (NZB/NZW)F1 mice.

    PubMed

    Gu, Fei; Molano, Ivan; Ruiz, Philip; Sun, Lingyun; Gilkeson, Gary S

    2012-11-01

    MSC are being explored as a promising novel treatment for SLE. In this study, we: 1) assessed the differential effects of allogeneic versus syngeneic MSC transplantation on lupus-like disease, 2) explored the mechanisms by which MSC modulate disease, and 3) investigated whether lupus-derived-MSC have intrinsic immunomodulatory defects. We showed that in MRL/lpr mice and (NZB/NZW)F1 mice, both B6-MSC and lupus-MSC from young mice ameliorated SLE-like disease and reduced splenic CD3+CD4+ T lymphocytes and CD19+CD21+ B lymphocytes. However, lupus-MSC from older (NZB/NZW)F1 mice did not reduce spleen weights, glomerular IgG deposits, renal pathology, interstitial inflammation, CD3+CD4+ T lymphocytes or CD19+CD21+ B lymphocytes significantly. Thus MSC transplantation ameliorates SLE-like disease partly through decreasing CD4+ T cell and naïve mature B cell numbers. Allogeneic MSC may be preferred over syngeneic lupus-derived-MSC given the decreased overall effectiveness of post-lupus-derived-MSC, which appears partially due to disease and not exclusively intrinsic defects in the MSC themselves.

  12. Subcutaneous (SQ) injections

    MedlinePlus

    SQ injections; Sub-Q injections; Diabetes subcutaneous injection; Insulin subcutaneous injection ... NIH. Giving a subcutaneous injection . Rockville, MD. National ... of Health and Human Services NIH publications; 2015. Available ...

  13. A Simplified 4-Site Economical Intradermal Post-Exposure Rabies Vaccine Regimen: A Randomised Controlled Comparison with Standard Methods

    PubMed Central

    Warrell, Mary J.; Riddell, Anna; Yu, Ly-Mee; Phipps, Judith; Diggle, Linda; Bourhy, Hervé; Deeks, Jonathan J.; Fooks, Anthony R.; Audry, Laurent; Brookes, Sharon M.; Meslin, François-Xavier; Moxon, Richard; Pollard, Andrew J.; Warrell, David A.

    2008-01-01

    Background The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. Methods Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. Findings All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. Conclusions This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be

  14. Intradermal administration of endothelin-1 attenuates endothelium-dependent and -independent cutaneous vasodilation via Rho kinase in young adults.

    PubMed

    Fujii, Naoto; Amano, Tatsuro; Halili, Lyra; Louie, Jeffrey C; Zhang, Sarah Y; McNeely, Brendan D; Kenny, Glen P

    2017-01-01

    We recently showed that intradermal administration of endothelin-1 diminished endothelium-dependent and -independent cutaneous vasodilation. We evaluated the hypothesis that Rho kinase may be a mediator of this response. We also sought to evaluate if endothelin-1 increases sweating. In 12 adults (25 ± 6 yr), we measured cutaneous vascular conductance (CVC) and sweating during 1) endothelium-dependent vasodilation induced via administration of incremental doses of methacholine (0.25, 5, 100, and 2,000 mM each for 25 min) and 2) endothelium-independent vasodilation induced via administration of 50 mM sodium nitroprusside (20-25 min). Responses were evaluated at four skin sites treated with either 1) lactated Ringer solution (Control), 2) 400 nM endothelin-1, 3) 3 mM HA-1077 (Rho kinase inhibitor), or 4) endothelin-1+HA-1077. Pharmacological agents were intradermally administered via microdialysis. Relative to the Control site, endothelin-1 attenuated endothelium-dependent vasodilation (CVC at 2,000 mM methacholine, 80 ± 10 vs. 56 ± 15%max, P < 0.01); however, this response was not detected when the Rho kinase inhibitor was simultaneously administered (CVC at 2,000 mM methacholine for Rho kinase inhibitor vs. endothelin-1 + Rho kinase inhibitor sites: 73 ± 9 vs. 72 ± 11%max, P > 0.05). Endothelium-independent vasodilation was attenuated by endothelin-1 compared with the Control site (CVC, 92 ± 13 vs. 70 ± 14%max, P < 0.01). However, in the presence of Rho kinase inhibition, endothelin-1 did not affect endothelium-independent vasodilation (CVC at Rho kinase inhibitor vs. endothelin-1+Rho kinase inhibitor sites: 81 ± 9 vs. 86 ± 10%max, P > 0.05). There was no between-site difference in sweating throughout (P > 0.05). We show that in young adults, Rho kinase is an important mediator of the endothelin-1-mediated attenuation of endothelium-dependent and -independent cutaneous vasodilation, and that endothelin-1 does not increase sweating. Copyright © 2017 the

  15. A comparison of the intradermal and subcutaneous routes of influenza vaccination with A/New Jersey/76 (swine flu) and A/Victoria/75: report of a study and review of the literature.

    PubMed

    Halperin, W; Weiss, W I; Altman, R; Diamond, M A; Black, K J; Iaci, A W; Black, H C; Goldfield, M

    1979-12-01

    A trail of influenza vaccination, with use of bivalent split virus vaccine (A/New Jersey/76 and A/Victoria/75), was conducted to compare the immunogenicity and reactions when vaccine was given by the subcutaneous and intradermal routes. Volunteers 18 to 24 years old were randomized into equal groups, one group receiving 0.1 ml of vaccine intradermally and the other receiving 0.5 ml subcutaneously. For the A/Victoria vaccine, the immunogenicity of the intradermal route seemed superior; for A/New Jersey vaccine, the routes were equivalent. Adverse reactions were minimal and equivalent for both groups. In times of vaccine shortage, the intradermal route is considered to stretch vaccine supplies. Field trials of new influenza vaccines should include evaluation of the immunogenicity of and adverse reactions caused by the same vaccine given by different routes in varied dosages.

  16. Comparison of tensile strength among simple interrupted, cruciate, intradermal, and subdermal suture patterns for incision closure in ex vivo canine skin specimens.

    PubMed

    Zellner, Eric M; Hedlund, Cheryl S; Kraus, Karl H; Burton, Andrew F; Kieves, Nina R

    2016-06-15

    OBJECTIVE To compare suture placement time, tension at skin separation and suture line failure, and mode of failure among 4 suture patterns. DESIGN Randomized trial. SAMPLE 60 skin specimens from the pelvic limbs of 30 purpose-bred Beagles. PROCEDURES Skin specimens were harvested within 2 hours after euthanasia and tested within 6 hours after harvest. An 8-cm incision was made in each specimen and sutured with 1 of 4 randomly assigned suture patterns (simple interrupted, cruciate, intradermal, or subdermal). Suture placement time and percentage of skin apposition were evaluated. Specimens were mounted in a calibrated material testing machine and distracted until suture line failure. Tensile strength at skin-edge separation and suture-line failure and mode of failure were compared among the 4 patterns. RESULTS Mean suture placement time for the cruciate pattern was significantly less than that for other patterns. Percentage of skin apposition did not differ among the 4 patterns. Mean tensile strength at skin-edge separation and suture-line failure for the simple interrupted and cruciate patterns were significantly higher than those for the intradermal and subdermal patterns. Mean tensile strength at skin-edge separation and suture-line failure did not differ significantly between the intradermal and subdermal patterns or the simple interrupted and cruciate patterns. The primary mode of failure for the simple interrupted pattern was suture breakage, whereas that for the cruciate, intradermal, and subdermal patterns was tissue failure. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested external skin sutures may be preferred for closure of incisions under tension to reduce risk of dehiscence.

  17. Isolation and detection of Corynebacterium pseudotuberculosis in the reproductive organs and associated lymph nodes of non-pregnant does experimentally inoculated through intradermal route in chronic form.

    PubMed

    Latif, Nur Amirah Abdul; Abdullah, Faez Firdaus Jesse; Othman, Aishatu Mohammed; Rina, Adza; Chung, Eric Lim Teik; Zamri-Saad, Mohd; Saharee, Abdul Aziz; Haron, Abdul Wahid; Lila, Mohd Azmi Mohd

    2015-07-01

    Corynebacterium pseudotuberculosis is the etiological agent of caseous lymphadenitis that affects sheep and goats. This study was designed to determine the presence of the causative organism in the female reproductive organs and associated lymph nodes in non-pregnant does experimentally inoculated through intradermal route in the chronic form. 18 non-pregnant healthy Katjang does aged 2-year-old were divided randomly into two groups. The first and second group consists of nine non-pregnant does each and the two groups were subdivided into three subgroups. The first group was experimentally inoculated with 1 ml of 10(7)cfu of live C. pseudotuberculosis through intradermal route, whereas the second group was inoculated with 1 ml phosphate buffer saline (pH 7) solution intradermally. The first group were further subdivided into three subgroups where, the first subgroup (B1) were kept for 30 days post-infection, second subgroup (B2) were kept for 60 days post-infection, and third subgroup (B3) were kept for 90 days. The second group was further subdivided into three subgroups (C1, C2, and C3) where they were kept for 39, 60, and 90 days post-infection, respectively. From this study, there was successful isolation of C. pseudotuberculosis from the reproductive organs of the treatment group after 60 days post-infection. The subgroups (B1, C1, C2, and C3) did not show any presence of the causative organism in the reproductive organs. The second subgroup B2 and third subgroup B3 showed positive isolation of the causative organisms from the ovary, uterine horns, uterus, cervix, vagina, and inguinal lymph node of the experimental non-pregnant does. This study showed that chronic infection of C. pseudotuberculosis via intradermal route may cause effect toward the reproductive organs and may be able to influence the reproductive efficiency of the infected animals.

  18. TETANUS PROPHYLAXIS IN THE UNIMMUNIZED—Administration of Oxytetracycline and Intradermal Toxoid, with Restricted Use of Tetanus Antitoxin

    PubMed Central

    McDonald, Richard T.; Kirtland, Howard B.; Brown, Roland G.

    1962-01-01

    Prophylactic tetanus antitoxin is ineffective in the prevention of experimental tetanus. That this may be true clinically is indicated by the fact that there are increasing numbers of cases of tetanus in humans after prophylactic tetanus antitoxin. Despite this known ineffectiveness and the high rate of reaction to antitoxin (5 per cent), many physicians continue to use it prophylactically, apparently for medical legal reasons. Since tetanus in civilian wounds is so rare, occurring approximately once in every million wounds, the routine use of tetanus antitoxin will probably cause more harm than good. It has been demonstrated experimentally that oxytetracycline is the most effective antimicrobial in the prevention of tetanus. It is, therefore, believed that adequate tetanus prophylaxis may be obtained by meticulous debridement and cleansing of the wound, by the administration of 1 gm. oxytetracycline daily for five days, and by intradermal administration of tetanus toxoid on the first, fourth and seventh days. Tetanus antitoxin is not given unless contaminated wounds have ben neglected for eight hours or more. In these instances, 15,000 units or more of tetanus antitoxin is given. Tetanus toxoid remains the best wound prophylaxis and greater emphasis should be placed on immunizing entire populations. PMID:18732507

  19. [Case of 5 year-old boy with anaphylaxis due to erythritol with negative prick test and positive intradermal test].

    PubMed

    Kurihara, Kazuyuki; Suzuki, Tsuyoshi; Unno, Atsushi; Hatano, Michihiro

    2013-11-01

    A 5 year-old boy experienced anaphylaxis after eating a jelly product for diet supplement containing erythritol as a major component. Prick test with the jelly product was negative, but the second oral ingestion of the jelly product at home caused another allergic reaction. Prick test with erythritol was negative even at 300 mg/ml, which was almost the solubility limit. Intradermal test was marginally positive at 0.1 mg/ml, and clearly positive at 1 mg/ml or higher concentration. We found subtle dose-response reaction utilizing basophil activation test, examined with 24 hour incubation at the concentration of 40-4000 μg/ml. At the oral challenge test in the hospital, 3 g of erythritol induced remarkable coughing, urticaria, edema, wheezing and hypoxemia. Erythritol is a natural sugar alcohol, with the molecular weight of 122.12, which is recently being widely used for diet supplements, beverages, or drug medicines due to its properties of calorie-free and good-tasting, with easy-to-use physical characteristics. We now have to recognize erythritol as a candidate for food allergen, and to be careful about negative result of prick test.

  20. Performance of LBSap Vaccine after Intradermal Challenge with L. infantum and Saliva of Lu. longipalpis: Immunogenicity and Parasitological Evaluation

    PubMed Central

    Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Vitoriano-Souza, Juliana; Coura-Vital, Wendel; Braga, Samuel Leôncio; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa; de Lana, Marta; Gontijo, Nelder Figueiredo; Marques, Marcos José; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa

    2012-01-01

    In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21+) and both CD4+ and CD8+ T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4+ T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions. PMID:23189161

  1. Use of the intradermal tuberculin test in a herd of captive elk (Cervus elaphus nelsoni) naturally infected with Mycobacterium bovis.

    PubMed

    Palmer, Mitchell V; Whipple, Diana L; Payeur, Janet B; Bolin, Carole A

    2011-03-01

    In the United States, tuberculosis of captive cervids, caused by Mycobacterium bovis, attracted attention in 1991 when investigations, prompted by the identification of a tuberculous elk (Cervus elaphus nelsoni) of U.S. origin exported to Canada, revealed tuberculosis in 10 different elk herds in 8 different states. Based on methods used in cattle, official regulations pertaining to testing and eradication of tuberculosis in captive cervids were added to the U.S. Department of Agriculture bovine tuberculosis eradication effort in 1994. However, little published information exists on the accuracy of intradermal tuberculin testing in naturally infected cervids. Evaluation of a captive herd of 71 animals in Wisconsin included postmortem examination and tissue sample collection from both tuberculin test responders and nonresponders. Within this captive herd, of admittedly small size, results showed the single cervical test to have a sensitivity of 88% and a specificity of 69%. Evaluation of diagnostic tests in the species of interest is important, as extrapolation of data obtained from other species may not be appropriate.

  2. Intracutaneously injected human adipose tissue-derived stem cells in a mouse model stay at the site of injection.

    PubMed

    Koellensperger, E; Lampe, K; Beierfuss, A; Gramley, F; Germann, G; Leimer, U

    2014-06-01

    The aim of this study was to evaluate the local behavior of intracutaneously injected human mesenchymal stem cells from adipose tissue and to determine the safety of a cell-based cutaneous therapy in an animal model.Human mesenchymal stem cells from adipose tissue were labeled with red fluorochrome and were injected intradermally in the paravertebral area in immunodeficient BalbC/nude mice (n = 21). As a control, cell culturemedium was injected in the same fashion on the contralateral paravertebral side. Four weeks, 6 months, and 12 months after the injection, seven mice were examined. In addition to the injected areas, the lungs, kidneys,spleens, and brains were excised and processed for histological evaluation. Serial sections of all the tissues excised were evaluated for adipose tissue-derived stem cells by means of emerging red fluorescent signals.The injected stem cells could be detected throughout the follow-up period of 1-year at the injection site within the dermal and subcutaneous layers. Bar these areas, adipose tissue-derived stem cells were not found in any otherexamined tissue at any point in time. The adipose tissue-derived stem cells showed a slow transition to deeper subcutaneous adipose tissue layers and, in part, a differentiation into adipocytes. No ulceration, inflammation, ortumor induction could be detected.The present study shows that intracutaneously injected human mesenchymal stem cells from adipose tissue stay at the site of injection, survive in vivo for up to 1-year, and partly differentiate into adipocytes. This is a new andvery important finding needed to safely apply therapies based on such stem cells in fat transplants in regenerative medicine. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  3. Transient engraftment of syngeneic bone marrow after conditioning with high-dose cyclophosphamide and thoracoabdominal irradiation in a patient with aplastic anemia

    SciTech Connect

    Matsue, K.; Niki, T.; Shiobara, S.; Ueda, M.; Ohtake, S.; Mori, T.; Matsuda, T.; Harada, M. )

    1990-01-01

    We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high-dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non-HLA antigens. This case report implies that graft failure in some cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.

  4. Validation of syngeneic mouse models of melanoma and non-small cell lung cancer for investigating the anticancer effects of the soy-derived peptide Lunasin

    PubMed Central

    Devapatla, Bharat; Shidal, Chris; Yaddanapudi, Kavitha; Davis, Keith R.

    2017-01-01

    Background: Lunasin is a naturally occurring peptide present in soybean that has both chemopreventive and therapeutic activities that can prevent cellular transformation and inhibit the growth of several human cancer types. Recent studies indicate that Lunasin has several distinct potential modes of action including suppressing integrin signaling and epigenetic effects driven by modulation of histone acetylation. In addition to direct effects on cancer cells, Lunasin also has effects on innate immunity that may contribute to its ability to inhibit tumor growth in vivo. Methods : Standard assays for cell proliferation and colony formation were used to assess Lunasin’s in vitro activity against murine Lewis lung carcinoma (LLC) and B16-F0 melanoma cells.  Lunasin’s in vivo activity was assessed by comparing the growth of tumors initiated by subcutaneous implantation of LLC or B16-F0 cells in Lunasin-treated and untreated C57BL/6 mice. Results : Lunasin was found to inhibit growth of murine LLC cells and murine B16-F0 melanoma cells in vitro and in wild-type C57BL/6 mice.  The effects of Lunasin in these two mouse models were very similar to those previously observed in studies of human non-small cell lung cancer and melanoma cell lines. Conclusions : We have now validated two established syngeneic mouse models as being responsive to Lunasin treatment.  The validation of these two in vivo syngeneic models will allow detailed studies on the combined therapeutic and immune effects of Lunasin in a fully immunocompetent mouse model. PMID:28299174

  5. Linkage of superantigen-like stimulation of syngeneic T cells in a mouse model of follicular center B cell lymphoma to transcription of endogenous mammary tumor virus.

    PubMed Central

    Tsiagbe, V K; Yoshimoto, T; Asakawa, J; Cho, S Y; Meruelo, D; Thorbecke, G J

    1993-01-01

    The MHC class II I-A(s) positive B cell lymphomas reticulum cell sarcoma (RCS) that arise in > 90% of SJL mice by the age of 12 months have superantigen-like stimulating properties. In the present study, therefore, RCS cell lines were examined for abnormal expression of endogenous mouse mammary tumor virus (MMTV) proviruses. Extraordinarily high expression of a 1.8 kb mRNA hybridizing with the long terminal repeat (LTR) of MMTV was found in both primary lymphomas and in vitro RCS lines, but not in an SJL B cell lymphoma, NJ101, that does not stimulate syngeneic T cells, or in LPS activated SJL B cells. A cDNA was cloned from cRCS-2 and sequenced. A 31mer oligonucleotide probe, prepared based on the unique C-terminal sequence of this RCS-Mtv LTR, detected the 1.8 kb mRNA in all RCS lymphomas, while a similar probe for the C-terminal sequence of Mtv-8 LTR hybridized with the larger mRNA present in normal B cells and in NJ101. Preincubation with 19mer antisense S-oligonucleotides, prepared based on the sequences of the first two potential translation initiation sites common to both Mtv-8 and the RCS-Mtv LTR, significantly reduced the ability of RCS cells to stimulate syngeneic T cells. Moreover, transfection of NJ101 cells with the cloned RCS-MMTV cDNA conferred V beta 16 T cell stimulating properties on to these cells. It is concluded that expression of the product of this MMTV-LTR mRNA provides RCS with the strong T cell stimulating properties that it needs for its growth. These results thus identify a novel oncogenic property of MMTV-LTR. Images PMID:8389694

  6. Differential effects of BCNU on T cell, macrophage, natural killer and lymphokine-activated killer cell activities in mice bearing a syngeneic tumor.

    PubMed

    Nagarkatti, M; Nagarkatti, P S; Kaplan, A M

    1988-01-01

    Chloroethylnitrosoureas have been used widely to treat human and experimental animal tumors. We have earlier observed that greater than 90% of the mice transplanted with syngeneic tumors survive following treatment with nitrosoureas such as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and furthermore, they resist subsequent challenge with the same tumor. The present investigation was initiated to determine the mechanism by which BCNU brings about this effect. Treatment of tumor cell targets in vivo or in vitro with BCNU, increased their susceptibility to macrophage (M luminal diameter)-mediated cytotoxicity as measured in a direct cytotoxicity assay or in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. In contrast, the antitumor cytotoxicity caused by cytotoxic T lymphocytes (CTL), natural killer (NK) cells, or lymphokine-activated killer (LAK) cells, was not altered following BCNU treatment of tumor targets. Studies were also conducted to investigate the direct effect of BCNU in vivo on various cytotoxic effector cells. For this purpose, M luminal diameter, NK, LAK, and CTL activities from BCNU-treated-tumor-bearing mice were screened for cytotoxicity against untreated tumor targets in vitro. It was observed that tumor-specific CTL and LAK cell activity increased in BCNU-treated tumor-bearing mice when compared to untreated controls while the cytotoxic potential of NK cells and M luminal diameters was not altered. The present study suggests that antitumor drugs such as BCNU are not only tumoricidal but also selectively act in a variety of ways at both the effector and target cell level, leading to overall enhanced antitumor immunity and high rate of cures from the syngeneic tumor challenge.

  7. Mechanism of protection from graft-vs-host disease in murine mixed allogeneic chimeras. I. Development of a null cell population suppressive of cell-mediated lympholysis responses and derived from the syngeneic bone marrow component

    SciTech Connect

    Sykes, M.; Eisenthal, A.; Sachs, D.H.

    1988-05-01

    Splenocyte populations from whole body-irradiated recipients of mixed T cell-depleted (TCD) syngeneic and allogeneic (complete H-2 disparity) bone marrow, or of TCD syngeneic marrow alone, contain cells with the ability to suppress the generation of cell-mediated lympholysis responses in vitro. This activity, which is present by 8 days after bone marrow transplantation and persists for several weeks, has been analyzed for possible veto-like or other specificity. Although reproducible patterns of suppression were observed, depending both on host strain and on the genetic combination of the response examined, the overall suppression in vitro most closely resembles that which has been ascribed to natural suppressor cells in other systems. The suppression appears to be mediated by a non-T cell, non-B cell, nonadherent, asialo GM1-negative population. Cold target inhibition and CTL activity of chimeric cells have been ruled out as factors contributing to the observed suppression. Significantly, in mixed chimeras, suppression was found to be mediated exclusively by cells which were syngeneic to the recipient in both recipient strains tested. The rapid development of this suppressive activity may explain the resistance to graft-vs-host disease conferred on whole body-irradiated mice by the addition of TCD syngeneic marrow to an allogeneic graft-vs-host disease-producing inoculum.

  8. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects.

    PubMed

    Frey, Sharon E; Wald, Anna; Edupuganti, Srilatha; Jackson, Lisa A; Stapleton, Jack T; El Sahly, Hana; El-Kamary, Samer S; Edwards, Kathryn; Keyserling, Harry; Winokur, Patricia; Keitel, Wendy; Hill, Heather; Goll, Johannes B; Anderson, Edwin L; Graham, Irene L; Johnston, Christine; Mulligan, Mark; Rouphael, Nadine; Atmar, Robert; Patel, Shital; Chen, Wilbur; Kotloff, Karen; Creech, C Buddy; Chaplin, Paul; Belshe, Robert B

    2015-09-22

    Modified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1×10(8) TCID50 in a volume of 0.5mL. This study compared the safety and immunogenicity of the standard formulation, dose and route with both a more stable, lyophilized formulation and with an antigen-sparing intradermal (ID) route of administration. 524 subjects were randomized to receive either a full dose of Lyophilized-SC, a full dose of Liquid-SC or 20% (2×10(7) TCID50 in 0.1mL) of a full dose Liquid-ID MVA on Days 0 and 28. Safety and immunogenicity were followed through 180 days post second vaccination. Among the 3 groups, the proportion of subjects with moderate/severe functional local reactions was significantly different (P=0.0013) between the Lyophilized-SC group (30.3%), the Liquid-SC group (13.8%) and Liquid-ID group (22.0%) only after first vaccination; and for moderate/severe measured erythema and/or induration after any vaccination (P=0.0001) between the Lyophilized-SC group (58.2%), the Liquid-SC group (58.1%) and the Liquid-ID group (94.8%) and the reactions lasted longer in the Liquid-ID group. In the ID Group, 36.1% of subjects had mild injection site skin discoloration lasting ≥6 months. After second vaccination Day (42-208), geometric mean of peak neutralization titers were 87.8, 49.5 and 59.5 for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively, and the maximum number of responders based on peak titer in each group was 142/145 (97.9%), 142/149 (95.3%) and 138/146 (94.5%), respectively. At 180 days after the second vaccination, geometric mean neutralization titers declined to 11.7, 10.2 and 10.4 with only 54.3%, 39.2% and 35.2% of subjects remaining seropositive for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively. Both the Lyophilized-SC and Liquid-ID groups were considered non-inferior (primary

  9. Evidence of Mycobacterium tuberculosis complex bacteraemia in intradermal skin test positive cattle detected using phage-RPA.

    PubMed

    Swift, Benjamin M C; Convery, Thomas W; Rees, Catherine E D

    2016-10-02

    Bovine tuberculosis is a zoonotic infectious disease caused by Mycobacterium bovis that affects cattle and can cause tuberculosis in a range of wildlife animals. A bacteriophage-based method combined with PCR (phage-PCR) has been recently used to detect and identify viable pathogenic mycobacteria in the peripheral blood mononuclear cells (PBMCs) of animals suffering from paratuberculosis. To adapt this method for the detection of M. bovis in blood, a new isothermal DNA amplification protocol using Recombinase Polymerase Amplification (RPA) was developed and was found to be able to detect M. bovis BCG within 48 h, with a limit of detection of approximately 10 cells per ml of blood for artificially inoculated blood samples. When blood samples (2 ml) from a Single Comparative Cervical Intradermal Tuberculin (SCCIT)- negative beef herd were tested, Mycobacterium tuberculosis complex (MTC) cells were not detected from any (45) of the blood samples. However when blood samples from SCCIT-positive animals were tested, viable MTC bacteria were detected in 66 % (27/41) of samples. Of these 41 animals sampled, 32 % (13) had visible lesions. In the visible lesion (VL) group, 85 % (11/13) had detectable levels of MTC whereas only 57 % (16/28) of animals which had no visible lesions (NVL) were found to have detectable mycobacteraemia. These results indicated that this simple, rapid method can be applied for the study of M. bovis infections. The frequency with which viable mycobacteria were detected in the peripheral blood of SCCIT-positive animals changes the paradigm of this disease.

  10. Intradermal administration of ATP augments methacholine-induced cutaneous vasodilation but not sweating in young males and females.

    PubMed

    Fujii, Naoto; Halili, Lyra; Singh, Maya Sarah; Meade, Robert D; Kenny, Glen P

    2015-10-15

    Acetylcholine released from cholinergic nerves is a key neurotransmitter contributing to heat stress-induced cutaneous vasodilation and sweating. Given that sympathetic cholinergic nerves also release ATP, ATP may play an important role in modulating cholinergic cutaneous vasodilation and sweating. However, the pattern of response may differ between males and females given reports of sex-related differences in the peripheral mechanisms governing these heat loss responses. Cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were evaluated in 17 young adults (8 males, 9 females) at four intradermal microdialysis skin sites continuously perfused with: 1) lactated Ringer (Control), 2) 0.3 mM ATP, 3) 3 mM ATP, or 4) 30 mM ATP. At all skin sites, methacholine was coadministered in a concentration-dependent manner (0.0125, 0.25, 5, 100, 2,000 mM, each for 25 min). In both males and females, CVC was elevated with the lone infusion of 30 mM ATP (both P < 0.05), but not with 0.3 and 3 mM ATP compared with control (all P >0.27). However, 0.3 mM ATP induced a greater increase in CVC compared with control in response to 100 mM methacholine infusion in males (P < 0.05). In females, 0.3 mM ATP infusion resulted in a lower concentration of methacholine required to elicit a half-maximal response (EC50) (P < 0.05). In both males and females, methacholine-induced sweating was unaffected by any concentration of ATP (all P > 0.44). We demonstrate that ATP enhances cholinergic cutaneous vasodilation albeit the pattern of response differs between males and females. Furthermore, we show that ATP does not modulate cholinergic sweating.

  11. Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

    PubMed Central

    Luo, Qingwei; Vickers, Tim J.

    2016-01-01

    Enterotoxigenic Escherichia coli (ETEC) strains are a common cause of diarrhea. Extraordinary antigenic diversity has prompted a search for conserved antigens to complement canonical approaches to ETEC vaccine development. EtpA, an immunogenic extracellular ETEC adhesin relatively conserved in the ETEC pathovar, has previously been shown to be a protective antigen following intranasal immunization. These studies were undertaken to explore alternative routes of EtpA vaccination that would permit use of a double mutant (R192G L211A) heat-labile toxin (dmLT) adjuvant. Here, oral vaccination with EtpA adjuvanted with dmLT afforded significant protection against small intestinal colonization, and the degree of protection correlated with fecal IgG, IgA, or total fecal antibody responses to EtpA. Sublingual vaccination yielded compartmentalized mucosal immune responses with significant increases in anti-EtpA fecal IgG and IgA, and mice vaccinated via this route were also protected against colonization. In contrast, while intradermal (i.d.) vaccination achieved high levels of both serum and fecal antibodies against both EtpA and dmLT, mice vaccinated via the i.d. route were not protected against subsequent colonization and the avidity of serum IgG and IgA EtpA-specific antibodies was significantly lower after i.d. immunization compared to other routes. Finally, we demonstrate that antiserum from vaccinated mice significantly impairs binding of LT to cognate GM1 receptors and shows near complete neutralization of toxin delivery by ETEC in vitro. Collectively, these data provide further evidence that EtpA could complement future vaccine strategies but also suggest that additional effort will be required to optimize its use as a protective immunogen. PMID:27226279

  12. Intradermal administration of ATP augments methacholine-induced cutaneous vasodilation but not sweating in young males and females

    PubMed Central

    Fujii, Naoto; Halili, Lyra; Singh, Maya Sarah; Meade, Robert D.

    2015-01-01

    Acetylcholine released from cholinergic nerves is a key neurotransmitter contributing to heat stress-induced cutaneous vasodilation and sweating. Given that sympathetic cholinergic nerves also release ATP, ATP may play an important role in modulating cholinergic cutaneous vasodilation and sweating. However, the pattern of response may differ between males and females given reports of sex-related differences in the peripheral mechanisms governing these heat loss responses. Cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were evaluated in 17 young adults (8 males, 9 females) at four intradermal microdialysis skin sites continuously perfused with: 1) lactated Ringer (Control), 2) 0.3 mM ATP, 3) 3 mM ATP, or 4) 30 mM ATP. At all skin sites, methacholine was coadministered in a concentration-dependent manner (0.0125, 0.25, 5, 100, 2,000 mM, each for 25 min). In both males and females, CVC was elevated with the lone infusion of 30 mM ATP (both P < 0.05), but not with 0.3 and 3 mM ATP compared with control (all P >0.27). However, 0.3 mM ATP induced a greater increase in CVC compared with control in response to 100 mM methacholine infusion in males (P < 0.05). In females, 0.3 mM ATP infusion resulted in a lower concentration of methacholine required to elicit a half-maximal response (EC50) (P < 0.05). In both males and females, methacholine-induced sweating was unaffected by any concentration of ATP (all P > 0.44). We demonstrate that ATP enhances cholinergic cutaneous vasodilation albeit the pattern of response differs between males and females. Furthermore, we show that ATP does not modulate cholinergic sweating. PMID:26290105

  13. Engraftment of Syngeneic and Allogeneic Endothelial Cells, Hepatocytes and Cholangiocytes into Partially Hepatectomized Rats Previously Treated with Mitomycin C1

    PubMed Central

    Brilliant, Kate E.; Mills, David R.; Callanan, Helen M.; Hixson, Douglas C.

    2009-01-01

    Background Pretreatment with retrorsine crosslinks host hepatocyte DNA and prevents proliferation after partial hepatectomy (PH), allowing selective expansion of transplanted progenitors. Shortcomings are length of protocol and carcinogenicity of retrorsine. Methods This report describes a rapid liver repopulation protocol using mitomycin C (MMC) to block proliferation of rat hepatocytes in response to PH. One week post-MMC treatment, dipeptidyl peptidase IV negative (DPPIV−) host rats were given a PH followed by injection of late gestation, newborn or adult total liver isolates from DPPIV+ rats. For allogeneic transplantation, host rats received injections of anti-CD3 antibody before and after PH. Results Host liver staining 2–9 weeks post-transplantation revealed well-defined donor hepatocyte colonies with strong canalicular DPPIV activity. At the same cell dose, fetal and newborn isolates produced more colonies than adult liver isolates. Hepatocyte colonies also co-expressed marker proteins characteristic of adult hepatocytes and showed polarized localization of plasma membrane proteins. Host livers contained large clusters of sinusoids lined by DPPIV+ endothelial cells co-expressing the endothelial cell marker, RECA-1 but lacked the canalicular marker leucine aminopeptidase. Colonies containing donor hepatocytes, endothelial cells and bile ducts, were also observed. Similar levels of engraftment and expansion were achieved with allogeneic liver cell isolates by using anti-CD3 antibody treatment. Conclusions The MMC transplantation model provides a rapid method for engraftment and expansion of hepatocytes, endothelial cells and cholangiocytes and should be applicable to investigations centering on the role of endothelial cells in liver regeneration and the identification and characterization of putative endothelial, hepatocyte and cholangiocyte progenitors. PMID:19696631

  14. Randomized Controlled Trial to Compare Immunogenicity of Standard-Dose Intramuscular Versus Intradermal Trivalent Inactivated Influenza Vaccine in HIV-Infected Men Who Have Sex With Men in Bangkok, Thailand.

    PubMed

    Garg, Shikha; Thongcharoen, Prasert; Praphasiri, Prabda; Chitwarakorn, Anupong; Sathirapanya, Pornchai; Fernandez, Stefan; Rungrojcharoenkit, Kamonthip; Chonwattana, Wannee; Mock, Philip A; Sukwicha, Wichuda; Katz, Jacqueline M; Widdowson, Marc-Alain; Curlin, Marcel E; Gibbons, Robert V; Holtz, Timothy H; Dawood, Fatimah S; Olsen, Sonja J

    2016-02-01

    Individuals infected with human immunodeficiency virus (HIV) are at increased risk for severe influenza, yet immune responses to standard-dose intramuscular (IM) influenza vaccine are suboptimal in this population. Intradermal (ID) delivery of influenza vaccine might improve immune response through enhanced stimulation of dendritic cells. We conducted a randomized, double-blind, controlled trial to compare the immunogenicity of off-label standard-dose (15 µg) ID vs standard-dose (15 µg) IM inactive influenza vaccine in HIV-infected men in Bangkok, Thailand. The primary study outcome was seroconversion (minimum titer of 1:40 and ≥4-fold rise in antibody titer) at 1 month postvaccination based on serum hemagglutination inhibition antibody titers against each vaccine strain. Adverse events (AEs) in the 7 days following vaccination were also assessed. We enrolled 400 HIV-infected participants; 200 were randomly assigned to receive IM and 200 ID vaccine. Vaccine arms were well-balanced with respect to age, CD4 cell count, HIV RNA load, and antiretroviral treatment. Percentage of seroconversion to all (ID 14% vs IM 15%; P = .8) or at least 1 (ID 69% vs IM 68%; P = .7) of the 3 vaccine strains did not differ significantly between ID vs IM vaccine recipients. A higher proportion of participants who received ID vaccine had mild injection-site AEs compared with participants who received IM vaccine (77% vs 27%). There were no significant differences in the immunogenicity of standard-dose ID vs IM influenza vaccine in this HIV-infected population in Thailand. Additional strategies to enhance immune responses to influenza vaccine among HIV-infected persons are needed. NCT01538940. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  15. Security and biomechanical strength of three end-pass configurations for the terminal end of intradermal closures performed with unidirectional barbed suture material in dogs.

    PubMed

    Regier, Penny J; Smeak, Daniel D; McGilvray, Kirk C

    2016-12-01

    OBJECTIVE To compare security of continuous intradermal suture lines closed by use of barbed suture with 3 end-pass configurations or without an end-pass configuration. SAMPLE 40 full-thickness, 4-cm-long, parasagittal wounds in canine cadavers. PROCEDURES Each continuous intradermal closure was terminated with 1 of 3 end-pass techniques or without an end-pass configuration (control group). A servohydraulic machine applied tensile load perpendicular to the long axis of the suture line. A load-displacement curve was generated for each sample; maximum load, displacement, stiffness, mode of construct failure, and load at first suture slippage at termination (ie, terminal end of the suture line) were recorded. RESULTS Values for maximum load, displacement, and stiffness did not differ significantly among the 3 end-pass techniques, and load at first suture slippage at termination was not significantly different among the 4 groups. A 1-pass technique slipped in 5 of 9 samples; 3 of these 5 slips caused failure of wound closure. A 2-pass technique slipped in 3 of 9 samples, none of which caused failure of wound closure. Another 2-pass technique slipped in 4 of 10 samples; 2 of these 4 slips caused failure of wound closure. The control group had slippage in 10 of 10 samples; 9 of 10 slips caused failure of wound closure CONCLUSIONS AND CLINICAL RELEVANCE An end-pass anchor was necessary to terminate a continuous intradermal suture line, and all 3 end-pass anchor techniques were suitable to prevent wound disruption. The 2-pass technique for which none of the suture slippages caused wound closure failure provided the most reliable configuration.

  16. Adjuvanted, antigen loaded N-trimethyl chitosan nanoparticles for nasal and intradermal vaccination: adjuvant- and site-dependent immunogenicity in mice.

    PubMed

    Bal, Suzanne M; Slütter, Bram; Verheul, Rolf; Bouwstra, Joke A; Jiskoot, Wim

    2012-03-12

    N-trimethyl chitosan (TMC) nanoparticles have been shown to increase the immunogenicity of subunit antigens after nasal and intradermal administration. This work describes a second generation of TMC nanoparticles containing ovalbumin as a model antigen (TMC/OVA nanoparticles) and an immunopotentiator (TMC/OVA/immunopotentiator nanoparticles). The selection of immunopotentiators included Toll-like receptor (TLR) ligands lipopolysaccharide (LPS), PAM(3)CSK(4) (PAM), CpG DNA, the NOD-like receptor 2 ligand muramyl dipeptide (MDP) and the GM1 ganglioside receptor ligand, cholera toxin B subunit (CTB). The TMC/OVA/immunopotentiator nanoparticles were characterised physico-chemically and their immunogenicity was assessed by determining the serum IgG, IgG1, IgG2a titres and secretory IgA levels in nasal washes after intradermal and nasal vaccination in mice. After nasal vaccination, TMC/OVA nanoparticles containing LPS or MDP elicited higher IgG, IgG1 and sIgA levels than non-adjuvanted TMC/OVA particles, whereas nanoparticles containing CTB, PAM or CpG did not. After intradermal vaccination, the TMC/OVA/CpG and TMC/OVA/LPS nanoparticles provoked higher IgG titres than plain TMC/OVA particles. Altogether, our results show that co-encapsulation of an additional immunopotentiator with the antigen into TMC nanoparticles can further improve the immunogenicity of the vaccine. However, the strength and quality of the response depends on the immunopotentiator as well as the route of administration. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Enhanced Immunogenicity of an HIV-1 DNA Vaccine Delivered with Electroporation via Combined Intramuscular and Intradermal Routes

    PubMed Central

    McKay, Paul F.; Fiserova, Anezka; Klein, Katja; Cope, Alethea; Rogers, Paul; Swales, Julie; Seaman, Michael S.; Combadiere, Behazine

    2014-01-01

    ABSTRACT It is accepted that an effective prophylactic HIV-1 vaccine is likely to have the greatest impact on viral transmission rates. As previous reports have implicated DNA-priming, protein boost regimens to be efficient activators of humoral responses, we sought to optimize this regimen to further augment vaccine immunogenicity. Here we evaluated single versus concurrent intradermal (i.d.) and intramuscular (i.m.) vaccinations as a DNA-priming strategy for their abilities to elicit humoral and cellular responses against a model HIV-1 vaccine antigen, CN54-gp140. To further augment vaccine-elicited T and B cell responses, we enhanced cellular transfection with electroporation and then boosted the DNA-primed responses with homologous protein delivered subcutaneously (s.c.), intranasally (i.n.), i.m., or transcutaneously (t.c.). In mice, the concurrent priming regimen resulted in significantly elevated gamma interferon T cell responses and high-avidity antigen-specific IgG B cell responses, a hallmark of B cell maturation. Protein boosting of the concurrent DNA strategy further enhanced IgG concentrations but had little impact on T cell reactivity. Interestingly protein boosting by the subcutaneous route increased antibody avidity to a greater extent than protein boosting by either the i.m., i.n., or t.c. route, suggesting that this route may be preferential for driving B cell maturation. Using an alternative and larger animal model, the rabbit, we found the concurrent DNA-priming strategy followed by s.c. protein boosting to again be capable of eliciting high-avidity humoral responses and to also be able to neutralize HIV-1 pseudoviruses from diverse clades (clades A, B, and C). Taken together, we show that concurrent multiple-route DNA vaccinations induce strong cellular immunity, in addition to potent and high-avidity humoral immune responses. IMPORTANCE The route of vaccination has profound effects on prevailing immune responses. Due to the insufficient

  18. Effects of repeated comparative intradermal tuberculin testing on test results: a longitudinal study in TB-free red deer.

    PubMed

    Che-Amat, Azlan; Risalde, Maria Ángeles; González-Barrio, David; Ortíz, Jose Antonio; Gortázar, Christian

    2016-09-05

    Diagnosing tuberculosis (TB) in farmed red deer (Cervus elaphus) is challenging and might require combining cellular and humoral diagnostic tests. Repeated skin-testing with mycobacterial purified protein derivatives (PPDs) might sensitize or desensitize the subjects to both kinds of diagnostic tools. We evaluated the effect of repeated (every 6 months) comparative tuberculin skin testing on skin test and ELISA responsiveness in farmed red deer hinds from a TB-free herd. Eighteen 8-month old hinds were inoculated with bovine and avian PPDs and the mitogen phytohaemagglutinin (PHA), as positive control and concurrently tested by ELISA for antibodies against avian (avian PPD, aPPD and protoplasmatic antigen 3, PPA3) and bovine antigens (bPPD and MPB70). Blood serum was also sampled three weeks after each skin testing round and tested for antibodies against aPPD and bPPD, in order to detect eventual antibody level boosts. Testing took place every six months from winter 2012 until winter 2015. The skin test response to both PPDs peaked during the second and third test round, returning to standard values thereafter. Individual variability was particularly high at the first year and early second year testing rounds (first intradermal test and blood sampling; first winter). The antibody response to avian antigens increased through time, while no such increase was recorded for bovine antigens. The antibody boost three weeks after skin testing was more marked for avian PPD. However, there was no consistent trend in the boosting response through time. Repeated comparative skin testing at six month intervals did not cause progressive increments in skin test responsiveness or antibody production. Specifically, we observed no loss of the skin test response to bPPD and also no progressive loss of the boosting effect in the ELISA responses. However, we recorded increases through time in the antibody levels against avian mycobacterial antigens, possibly due to the progressive

  19. Exploring the mechanisms underpinning sweating: the development of a specialized ventilated capsule for use with intradermal microdialysis.

    PubMed

    Meade, Robert D; Louie, Jeffrey C; Poirier, Martin P; McGinn, Ryan; Fujii, Naoto; Kenny, Glen P

    2016-03-01

    Many studies have aimed to identify the controllers of sweating using ventilated capsules with intradermal microdialysis. It is unclear, however, if the surface area covered by the capsule influences the observed response as a result of differences in the number of sweat glands affected by the infused pharmacological agent relative to the total glands captured by the capsule. We evaluated the area of skin perfused with agents delivered via microdialysis. Thereafter, we developed a specialized sweat capsule (1.1 cm(2)) and compared the sweating response with a classic capsule (2.8 cm(2)). InProtocol 1(n = 6), methacholine was delivered to forearm skin in a dose-dependent manner (1-2000 mmol L(-1)). The area of activated sweat glands was assessed via the modified iodine-paper technique. InProtocol 2(n = 6), the area of inhibited sweat glands induced by ouabain and atropine was assessed during moderate-intensity cycling. Marked variability in the affected skin area was observed (0.9 ± 0.4 to 5.2 ± 1.1 cm(2)). InProtocol 3(n = 6), we compared the attenuation in local sweat rate (LSR) induced by atropine between the new and classic capsule during moderate-intensity cycling. Atropine attenuated sweating as assessed using the new (control: 0.87 ± 0.23 mg min(-1) cm(-2)vs. atropine: 0.54 ± 0.22 mg min(-1) cm(-2);P < 0.01) and classic (control: 0.85 ± 0.33 mg min(-1) cm(-2)vs. atropine: 0.60 ± 0.26 mg min(-1) cm(-2);P = 0.05) capsule designs. Importantly, responses did not differ between capsule designs (P = 0.23). These findings provide critical information regarding the skin surface area perfused by microdialysis and suggest that use of a larger capsule does not alter the mechanistic insight into the sweating response gained when using microdialysis.

  20. Successful immunotherapy of canine flea allergy with injected Actinomycetales preparations.

    PubMed

    Marro, Alicia; Pirles, Mónica; Schiaffino, Laura; Bin, Liliana; Dávila, Héctor; Bottasso, Oscar A; McIntyre, Graham; Ripley, Paul R; Stanford, Cynthia A; Stanford, John L

    2011-08-01

    Can heat-killed, borate-buffered suspensions of Gordonia bronchialis, Rhodococcus coprophilus or Tsukamurella inchonensis be used to treat canine flea allergy? Organisms cultured on Sauton's medium into stationary phase were autoclaved in borate-buffered saline and stored at 10 mg wet weight/ml. Intradermal injections of 0.1 ml containing 1 mg of bacilli were administered on the first and 20th days of the study. G. bronchialis and R. coprophilus were most effective in a pilot study of a small number of dogs with flea allergy. A larger number of affected dogs were then randomized to receive placebo or either of the two selected reagents. The extent and severity of allergic signs and symptoms were scored and blood samples were collected just before the first injection and 28 days after the second. Both selected reagents reduced the extent and severity of lesions (p < 0.001) and reduced scratching. Eosinophil numbers were reduced (p < 0.0001) between the first and second assessment. Injections of G. bronchialis or R. coprophilus effectively reduce the signs and symptoms of flea allergy in dogs.

  1. Darbepoetin Alfa Injection

    MedlinePlus

    ... to inject it.Darbepoetin alfa injection comes in prefilled syringes and in vials to be used with disposable ... solution before injecting it. Be sure that the prefilled syringe or vial is labeled with the correct name ...

  2. Defining the Ideal Injection Techniques When Using 5-mm Needles in Children and Adults

    PubMed Central

    Hofman, Paul Leslie; Derraik, José Guilherme Behrensdorf; Pinto, Teresa Elizabeth; Tregurtha, Sheryl; Faherty, Ann; Peart, Jane Michele; Drury, Paul Leslie; Robinson, Elizabeth; Tehranchi, Ramin; Donsmark, Morten; Cutfield, Wayne Stephen

    2010-01-01

    OBJECTIVE We aimed to establish the ideal injection techniques using 5-mm needles to reliably inject insulin into the subcutaneous fat in both children and adults and to quantify the associated pain and leakage of the test medium. RESEARCH DESIGN AND METHODS A total of 259 subjects (122 children/adolescents and 137 adults) were injected with sterile air corresponding to 20 IU insulin (200 μl) with 32-G 5-mm needles at 90° or 45°, in the abdomen and thigh, and with or without a pinched skin fold. Injection depth was assessed via ultrasonography. Subjects rated pain on a visual analog scale. Test medium injections into the abdomen and thigh (0.2–0.6 ml) were also administered to assess injection leakage. RESULTS Among children, 5.5% of injections were intramuscular (IM) and 0.5% were intradermal, while in adults, the incidence was 1.3 and 0.6%, respectively. The frequency of IM injections was greater in boys and negligible among adult women. Subcutaneous fat thickness was the primary predictor of the likelihood of IM injections (P < 0.001). A third of all patients reported experiencing no pain during insulin injection, with children/adolescents experiencing considerably more discomfort than adults. Some leakage of medium was observed, but was unrelated to injection volume and was generally minimal. CONCLUSIONS 5-mm needles are reliably inserted into subcutaneous fat in both adults and children. These needles were associated with reduced pain and minimal leakage. We recommend an angled injection with a pinched skin fold for children, while in adults, the technique should be left to patient preference. PMID:20585002

  3. Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation.

    PubMed

    Schönland, Stefan O; Lokhorst, Henk; Buzyn, Agnes; Leblond, Veronique; Hegenbart, Ute; Bandini, Giuseppe; Campbell, Andrew; Carreras, Enric; Ferrant, Augustin; Grommisch, Leanthe; Jacobs, Peter; Kröger, Nicolaus; La Nasa, Giorgio; Russell, Nigel; Zachee, Pierre; Goldschmidt, Hartmut; Iacobelli, Simona; Niederwieser, Dietger; Gahrton, Gösta

    2006-03-15

    Using the European Group for Blood and Marrow Transplantation (EBMT) registry, we retrospectively studied 19 patients with AL (amyloid light-chain) amyloidosis who underwent allogeneic (allo; n = 15) or syngeneic (syn; n = 4) hematopoietic stem cell transplantation (SCT) between 1991 and 2003. For allo-SCT, full-intensity conditioning was used in 7 patients and reduced-intensity conditioning (RIC) in 8 patients. Engraftment was durable in 12 of those 15 patients. The median follow-up time is 19 months. Kaplan-Meier probabilities of overall and progression-free survival were 60% and 53% at 1 year, respectively. Overall, 40% of patients died of transplant-related mortality (TRM). Best hematologic response after SCT was complete remission (CR) and partial remission (PR) in 8 and 2 patients, respectively, leading to an organ response in 8 of these patients. Seven of the 10 patients in remission are long-term survivors. In 5 of 7 evaluable patients in CR, chronic graft-versus-host disease (GvHD) was observed, indicating the contribution of immune effects to disease control. The main clinical problem was cardiac failure in patients with poor performance status due to amyloidosis or in combination with severe infections. These data suggest that allo-SCT might be a promising and potentially curative treatment modality for selected patients with AL amyloidosis.

  4. 16,16-Dimethyl prostaglandin E2 and/or syngeneic bone marrow transplantation increase mouse survival after supra-lethal total body irradiation

    SciTech Connect

    Berk, L.B.; Patrene, K.D.; Boggs, S.S. )

    1990-06-01

    We evaluated the effects of 16,16-dimethyl prostaglandin E2 (dm-PGE2), with and without syngeneic bone marrow transplantation (BMT) on the survival and hematopoietic recovery of mice given 14-20 Gy total body irradiation (TBI). Survival of mice given combined dm-PGE2 and BMT was improved significantly over that of mice given either treatment alone. The 30-day survival after 14, 15, 16 or 18 Gy TBI for combined treatment was 97, 90, 20 or 10 percent, respectively. The corresponding 30-day survival rates for mice given BMT alone were 69, 60, 7 or 0 percent, respectively. For dm-PGE2 alone, 30-day survival was 63, 20, 10 or 0 percent, respectively. Deaths in both dm-PGE2 treated groups generally occurred after day 10 whereas deaths in the BMT group occurred before day 10. All irradiated controls were dead on or before day 10; after larger doses, deaths clustered around day 5. After 20 Gy TBI, all mice in all groups were dead by day 7. Studies of white blood cell recovery 1-9 days after 14 Gy TBI showed improvement with BMT, whereas dm-PGE2 did not enhance recovery. Nucleated cells per humerus, spleen weight, and spleen iron uptake (erythropoiesis) were also improved by BMT but not dm-PGE2.

  5. Gastritis in neonatal BALB/cCrSlc mice induced by immunization without adjuvant can be transferred to syngeneic nu/nu recipients.

    PubMed

    Greenwood, D L V; Sentry, J W

    2006-01-01

    The popularly exploited murine neonatal thymectomy experimental autoimmune gastritis (nTx:EAG) model requires the animal to be in a state of lymphopenia. Here we report on a novel murine immunization (without adjuvant) model that can establish a lasting gastritis. We demonstrate that the immunization model (imm:EAG) results in a bona fide autoimmune disease and define the resulting pathology and serology observed and compare it with that reported for human autoimmune gastritis. Immune cells present in the stomachs of imm:EAG gastritic mice include CD8 T cells, CD11b and Gr1 (granulocytes/monocytes) and B cells. We detected circulating antibodies of immunoglobulin G1 (IgG1) subclass, with some IgG(2a) and IgG(2b) reactive to stomach membranes and the parietal cell proton pump. The class and subclass of autoreactive antibodies resulting from imm:EAG suggest a T helper 1 (Th1)/Th2 immune response. We establish that both self-reactive T and B cells from BALB/cCrSlc imm:EAG gastritic mice have the potential to induce a gastritis in BALB/c syngeneic nu/nu recipients. We conclude that this model is likely to be superior to the currently popularly exploited nTx:EAG and provide insight into and an understanding of the mechanisms of and remedies for autoimmunity in an intact immune system.

  6. Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.

    PubMed

    Matthews, G M; Lefebure, M; Doyle, M A; Shortt, J; Ellul, J; Chesi, M; Banks, K M; Vidacs, E; Faulkner, D; Atadja, P; Bergsagel, P L; Johnstone, R W

    2013-09-12

    Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinostat, romidepsin) and novel combination therapies using in vitro human MM cell lines and in vivo preclinical screening utilizing syngeneic transplanted Vk*MYC MM. HDACi were combined with ABT-737, which targets the intrinsic apoptosis pathway, recombinant human tumour necrosis factor-related apoptosis-inducing ligand (rhTRAIL/MD5-1), that activates the extrinsic apoptosis pathway or the DNA methyl transferase inhibitor 5-azacytidine. We demonstrate that in vitro cell line-based studies provide some insight into drug activity and combination therapies that synergistically kill MM cells; however, they do not always predict in vivo preclinical efficacy or toxicity. Importantly, utilizing transplanted Vk*MYC MM, we report that panobinostat and 5-azacytidine synergize to prolong the survival of tumor-bearing mice. In contrast, combined HDACi/rhTRAIL-based strategies, while efficacious, demonstrated on-target dose-limiting toxicities that precluded prolonged treatment. Taken together, our studies provide evidence that the transplanted Vk*MYC model of MM is a useful screening tool for anti-MM drugs and should aid in the prioritization of novel drug testing in the clinic.

  7. Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma

    PubMed Central

    Matthews, G M; Lefebure, M; Doyle, M A; Shortt, J; Ellul, J; Chesi, M; Banks, K-M; Vidacs, E; Faulkner, D; Atadja, P; Bergsagel, P L; Johnstone, R W

    2013-01-01

    Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinostat, romidepsin) and novel combination therapies using in vitro human MM cell lines and in vivo preclinical screening utilizing syngeneic transplanted Vk*MYC MM. HDACi were combined with ABT-737, which targets the intrinsic apoptosis pathway, recombinant human tumour necrosis factor-related apoptosis-inducing ligand (rhTRAIL/MD5-1), that activates the extrinsic apoptosis pathway or the DNA methyl transferase inhibitor 5-azacytidine. We demonstrate that in vitro cell line-based studies provide some insight into drug activity and combination therapies that synergistically kill MM cells; however, they do not always predict in vivo preclinical efficacy or toxicity. Importantly, utilizing transplanted Vk*MYC MM, we report that panobinostat and 5-azacytidine synergize to prolong the survival of tumor-bearing mice. In contrast, combined HDACi/rhTRAIL-based strategies, while efficacious, demonstrated on-target dose-limiting toxicities that precluded prolonged treatment. Taken together, our studies provide evidence that the transplanted Vk*MYC model of MM is a useful screening tool for anti-MM drugs and should aid in the prioritization of novel drug testing in the clinic. PMID:24030150

  8. Epidural Injections for Spinal Pain

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z Epidural Injections An epidural injection provides temporary or prolonged relief ... limitations of Epidural Injection? What is an Epidural Injection? An epidural injection is an injection of medication ...

  9. Biomechanical Testing and Histologic Examination of Intradermal Skin Closure in Dogs Using Barbed Suture Device and Non-Barbed Monofilament Suture.

    PubMed

    Law, Andy Y; Butler, James R; Patnaik, Sourav S; Cooley, James A; Elder, Steven H

    2017-01-01

    To compare the biomechanical strength and histologic features of 3-0 Glycomer™ 631 barbed suture (V-LOC™ 90 Absorbable Wound Closure Device, Covidien, Mansfield, MA) to non-barbed 3-0 Glycomer™ 631 suture (Biosyn™, Covidien) for intradermal skin wound closure in the dog. Randomized, factorial, in vivo. Eighteen purpose-bred, mature male, and female hound dogs. Eighteen adult hound dogs were randomly assigned to 1 of 3 groups designated by postoperative day of assessment. Six skin incisions were made along the dorsum in the thoracolumbar region of each dog with an equal number (n=3) randomly assigned to closure with barbed or non-barbed suture. Six dogs were euthanatized on postoperative days 3, 10, and 14, respectively. Two additional incisions were made on each dog after euthanasia for baseline data (Day 0). The skin incision specimens were harvested for biomechanical testing and histologic evaluation. Non-barbed closure had significantly higher maximum load at failure (P<.001) and stiffness (P<.001) than barbed closure regardless of day. The average tissue reaction score was significantly higher for barbed closure (P=.008), regardless of day. Suturing time for barbed closures was significantly shorter. There was no significant difference in frequency of complications between closures. Barbed Glycomer™ 631 closures had a significantly lower maximum load at failure and stiffness, and higher average tissue reaction scores, but showed no difference in short term outcome for intradermal closure of dorsally located skin incisions in dogs. © 2016 The American College of Veterinary Surgeons.

  10. Comparative Efficacies of Long-Term Serial Transplantation of Syngeneic, Allogeneic, Xenogeneic, or CTLA4Ig-Overproducing Xenogeneic Adipose Tissue-Derived Mesenchymal Stem Cells on Murine Systemic Lupus Erythematosus.

    PubMed

    Choi, Eun Wha; Lee, Hee Woo; Shin, Il Seob; Park, Ji Hyun; Yun, Tae Won; Youn, Hwa Young; Kim, Sung-Joo

    2016-01-01

    Allogeneic and xenogeneic transplantation are suitable alternatives for treating patients with stem cell defects and autoimmune diseases. The purpose of this study was to compare the effects of long-term serial transplantation of adipose tissue-derived mesenchymal stem cells (ASCs) from (NZB × NZW) F1 mice (syngeneic), BALB/c mice (allogeneic), or humans (xenogeneic) on systemic lupus erythematosus (SLE). The effects of transplanting human ASCs overproducing CTLA4Ig (CTLA4Ig-hASC) were also compared. Animals were divided into five experimental groups, according to the transplanted cell type. Approximately 500,000 ASCs were administered intravenously every 2 weeks from 6 to 60 weeks of age to all mice except for the control mice, which received saline. The human ASC groups (hASC and CTLA4Ig-hASC) showed a 13-week increase in average life spans and increased survival rates and decreased blood urea nitrogen, proteinuria, and glomerular IgG deposition. The allogeneic group also showed higher survival rates compared to those of the control, up to 40, 41, 42, 43, 44, 45, 52, and 53 weeks of age. Syngeneic ASC transplantation did not accelerate the mortality of the mice. The mean life span of both the syngeneic and allogeneic groups was prolonged for 6-7 weeks. Both human ASC groups displayed increased serum interleukin-10 and interleukin-4 levels, whereas both mouse ASC groups displayed significantly increased GM-CSF and interferon-γ levels in the serum. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic, CTLA4Ig-xenogeneic, and syngeneic transplantations. Long-term serial transplantation of the ASCs from various sources displayed different patterns of cytokine expression and humoral responses, but all of them increased life spans in an SLE mouse model.

  11. How Long Will I Be Blue? Prolonged Skin Staining Following Sentinel Lymph Node Biopsy Using Intradermal Patent Blue Dye

    PubMed Central

    Gumus, Metehan; Gumus, Hatice; Jones, Sue E; Jones, Peter A; Sever, Ali R; Weeks, Jennifer

    2013-01-01

    Summary Background Blue dye used for sentinel lymph node biopsy (SLNB) in breast cancer patients may cause prolonged skin discoloration at the site of injection. The aim of this study was to assess the duration of such skin discoloration. Patients and Methods 236 consecutive patients who had undergone breast conserving surgery and SLNB for breast cancer were reviewed prospectively from January 2007 to December 2009. Results Of the 236 patients, 2 had undergone bilateral surgery, and 41 had been examined in consecutive yearly reviews. Blue discoloration remained visible at the injection site after 12, 24, and > 36 months in 36.5, 23.6, and 8.6% of the patients, respectively. Conclusion The use of patent blue for identification of the sentinel lymph node in patients undergoing breast cancer surgery may result in prolonged discoloration of the skin at the injection site. PMID:24415970

  12. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice.

    PubMed Central

    Quddus, J; Johnson, K J; Gavalchin, J; Amento, E P; Chrisp, C E; Yung, R L; Richardson, B C

    1993-01-01

    Human antigen-specific CD4+ T cells become autoreactive after treatment with various DNA methylation inhibitors, including 5-azacytidine, procainamide, and hydralazine. This suggests a mechanism that could contribute to the development of some forms of autoimmunity. In this report we have asked whether T cells treated with DNA methylation inhibitors can induce autoimmunity. Murine CD4+ T cells were treated with 5-azacytidine or procainamide and were shown to respond to syngeneic antigen-presenting cells, similar to CD4+ human T cell clones treated with these drugs. Functional characterization demonstrated that cells treated with either drug spontaneously lysed syngeneic macrophages and secreted IL-4, IL-6, and IFN-gamma. Adoptive transfer of 5-azacytidine- or procainamide-treated cells into unirradiated syngeneic recipients induced an immune complex glomerulonephritis and IgG anti-DNA and antihistone antibodies. These experiments demonstrate that T cells treated with either of two distinct DNA methyltransferase inhibitors are sufficient to induce a lupus-like disease. It is possible that the lysis of macrophages, together with the release of cytokines promoting B cell differentiation, contributes to the autoantibody production and immune complex deposition. These results suggest that environmental agents that inhibit DNA methylation could interact with T cells in vivo to produce a lupus-like illness, a mechanism that could have relevance to drug-induced and idiopathic lupus. Images PMID:7686923

  13. Beam Injection into RHIC

    NASA Astrophysics Data System (ADS)

    Fischer, W.; Hahn, H.; Mackay, W. W.; Tsoupas, N.

    1997-05-01

    During the RHIC sextant test in January 1997 beam was injected into a sixth of one of the rings for the first time. We describe the injection zone and its bottlenecks, the application program to steer the beam and the injection kickers. We report on the commissioning of the injection systems and on measurements of the kickers.

  14. Possible migration and histopathological analysis of injections of polymethylmethacrylate in wistar rats.

    PubMed

    Neves, Rodrigo d'Eça; Herdt, Marcello Alberton; Wohlgemuth, Felipe Barbieri; Ely, Jorge Bins; de Vasconcellos, Zulmar Antonio Accioli; Bastos, José Caldeira Ferreira; d'Acampora, Armando José

    2012-01-01

    Objective. To evaluate the possible migration of polymethylmethacrylate after injections in various corporal compartments of Wistar rats. Methods. The experimental work consisted in the injection of PMMA in corporal compartments for later histopathological analysis of the locations of implants and of distant filtering organs. The dose applied in each implant was of 0.2 mL. The animals were divided into groups according to the location of the implant realized: group GB had intradermic injections in the glabella. Group SD had subdermal injections in dorsal subcutaneous tissue cells. Group IP had intraperitoneal injections in the abdomen. Group PD had intramuscular injections in the right rear leg. The rats were sacrificed 30 days after realization of the implants and tissue samples from the lung, liver, spleen, and kidney, and locations of implantation were removed for histopathological analysis. Results. Characteristic microspheres that were compatible with the presence of PMMA in any of the histological slides analyzed were not observed. One animal had an amorphous exogenous substance, with a histiocytic reaction. Twelve of the 16 lungs analyzed had locations of intraalveolar hemorrhaging. Two animals had nonspecific spleen alterations. Conclusion. The histopathological analysis of this study found no PMMA microspheres in any of the tissues analyzed.

  15. Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory.

    PubMed

    Elisbão, Maria do Carmo M; Baldy, José Luís da S; Bonametti, Ana Maria; Reiche, Edna Maria V; Morimoto, Helena K; Pontello, Rubens; Matsuo, Tiemi; Ferelle, Antônio; Neves, Jayme

    2003-12-01

    Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> or = 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 micrograms booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB--with intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine at 0, 1, and 6 months--carried out eight years before in 51 dentists.

  16. HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial

    PubMed Central

    Nilsson, Charlotta; Hejdeman, Bo; Godoy-Ramirez, Karina; Tecleab, Teghesti; Scarlatti, Gabriella; Bråve, Andreas; Earl, Patricia L.; Stout, Richard R.; Robb, Merlin L.; Shattock, Robin J.; Biberfeld, Gunnel; Sandström, Eric; Wahren, Britta

    2015-01-01

    Background We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers. Methods HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n=16) or without (n=9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA. Results The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p=0.6158). The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%). CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients. Conclusion Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use. Trial Registration International Standard

  17. Involvement of Fas/Fas-L and Bax/Bcl-2 systems in germ cell death following immunization with syngeneic testicular germ cells in mice.

    PubMed

    Kuerban, Maimaiti; Naito, Munekazu; Hirai, Shuichi; Terayama, Hayato; Qu, Ning; Musha, Muhetaerjiang; Ikeda, Ayumi; Koji, Takehiko; Itoh, Masahiro

    2012-01-01

    Experimental autoimmune orchitis (EAO) is characterized by T cell-dependent lymphocytic inflammation and seminiferous tubule damage, which can result in the death of germ cells. The aim of the present study is to investigate the roles of the Fas/Fas-L and Bax/Bcl-2 systems in the death of germ cells in mice with EAO that is induced by immunization with syngeneic testicular germ cells (TGC). The results using real-time reverse transcription-polymerase chain reaction and immunostaining show that many terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining germ cells were present in seminiferous tubules during the active inflammation stage, and these cells were persistently observed in the seminiferous epithelium until the postactive inflammation stage. Intratesticular mRNA expression levels of both Fas and Bax were increased during the active inflammation stage and were dramatically decreased during the post-active inflammation stage. In contrast, the intratesticular mRNA expression levels of both Fas-L and Bcl-2 did not show significant changes during the active inflammation stage but showed extreme increases during the post-active inflammation stage. Immunohistochemically, some Fas- and Bax-positive germ cells were detected during the active inflammation stage, but these were hardly found during the post-active inflammation stage. In contrast, some Fas-L- and Bcl-2-positive germ cells were found during the active inflammation stage, and many of these were also observed during the post-active inflammation stage. These results indicate that germ cell death during TGC-induced EAO is mediated by the Fas/Fas-L and Bax/Bcl-2 systems during the active inflammation stage but not during the post-active inflammation stage.

  18. Mito-tempol and dexrazoxane exhibit cardioprotective and chemotherapeutic effects through specific protein oxidation and autophagy in a syngeneic breast tumor preclinical model.

    PubMed

    Dickey, Jennifer S; Gonzalez, Yanira; Aryal, Baikuntha; Mog, Steven; Nakamura, Asako J; Redon, Christophe E; Baxa, Ulrich; Rosen, Elliot; Cheng, Gang; Zielonka, Jacek; Parekh, Palak; Mason, Karen P; Joseph, Joy; Kalyanaraman, Balaraman; Bonner, William; Herman, Eugene; Shacter, Emily; Rao, V Ashutosh

    2013-01-01

    Several front-line chemotherapeutics cause mitochondria-derived, oxidative stress-mediated cardiotoxicity. Iron chelators and other antioxidants have not completely succeeded in mitigating this effect. One hindrance to the development of cardioprotectants is the lack of physiologically-relevant animal models to simultaneously study antitumor activity and cardioprotection. Therefore, we optimized a syngeneic rat model and examined the mechanisms by which oxidative stress affects outcome. Immune-competent spontaneously hypertensive rats (SHRs) were implanted with passaged, SHR-derived, breast tumor cell line, SST-2. Tumor growth and cytokine responses (IL-1A, MCP-1, TNF-α) were observed for two weeks post-implantation. To demonstrate the utility of the SHR/SST-2 model for monitoring both anticancer efficacy and cardiotoxicity, we tested cardiotoxic doxorubicin alone and in combination with an established cardioprotectant, dexrazoxane, or a nitroxide conjugated to a triphenylphosphonium cation, Mito-Tempol (4) [Mito-T (4)]. As predicted, tumor reduction and cardiomyopathy were demonstrated by doxorubicin. We confirmed mitochondrial accumulation of Mito-T (4) in tumor and cardiac tissue. Dexrazoxane and Mito-T (4) ameliorated doxorubicin-induced cardiomyopathy without altering the antitumor activity. Both agents increased the pro-survival autophagy marker LC3-II and decreased the apoptosis marker caspase-3 in the heart, independently and in combination with doxorubicin. Histopathology and transmission electron microscopy demonstrated apoptosis, autophagy, and necrosis corresponding to cytotoxicity in the tumor and cardioprotection in the heart. Changes in serum levels of 8-oxo-dG-modified DNA and total protein carbonylation corresponded to cardioprotective activity. Finally, 2D-electrophoresis/mass spectrometry identified specific serum proteins oxidized under cardiotoxic conditions. Our results demonstrate the utility of the SHR/SST-2 model and the potential of

  19. Toxicology and efficacy of tumor-targeting Salmonella typhimurium A1-R compared to VNP 20009 in a syngeneic mouse tumor model in immunocompetent mice.

    PubMed

    Zhang, Yong; Cao, Wenluo; Toneri, Makoto; Zhang, Nan; Kiyuna, Tasuku; Murakami, Takashi; Nelson, Scott D; Dry, Sarah M; Li, Yunfeng; Li, Shukuan; Wang, Xiaoen; Ma, Huaiyu; Singh, Arun S; Eilber, Fritz C; Hoffman, Robert M; Zhao, Ming

    2017-08-15

    Salmonella typhimurium A1-R (S. typhimurium A1-R) attenuated by leu and arg auxotrophy has been shown to target multiple types of cancer in mouse models. In the present study, toxicologic and biodistribution studies of tumor-targeting S. typhimurium A1-R and S. typhimurium VNP20009 (VNP 20009) were performed in a syngeneic tumor model growing in immunocompetent BALB/c mice. Single or multiple doses of S. typhimurium A1-R of 2.5 × 10(5) and 5 × 10(5) were tolerated. A single dose of 1 × 10(6) resulted in mouse death. S. typhimurium A1-R (5 × 10(5) CFU) was eliminated from the circulation, liver and spleen approximately 3-5 days after bacterial administration via the tail vein, but remained in the tumor in high amounts. S. typhimurium A1-R was cleared from other organs much more rapidly. S. typhimurium A1-R and VNP 20009 toxicity to the spleen and liver was minimal. S. typhimurium A1-R showed higher selective targeting to the necrotic areas of the tumors than VNP20009. S. typhimurium A1-R inhibited the growth of CT26 colon carcinoma to a greater extent at the same dose of VNP20009. In conclusion, we have determined a safe dose and schedule of S. typhimurium A1-R administration in BALB/c mice, which is also efficacious against tumor growth. The results of the present report indicate similar toxicity of S. typhimurium A1-R and VNP20009, but greater antitumor efficacy of S. typhimurium A1-R in an immunocompetent animal. Since VNP2009 has already proven safe in a Phase I clinical trial, the present results indicate the high clinical potential of S. typhimurium A1-R.

  20. Prolonged survival in mice with advanced tumors treated with syngeneic or allogeneic intra-bone marrow-bone marrow transplantation plus fetal thymus transplantation.

    PubMed

    Hosaka, Naoki; Cui, Wenhao; Zhang, Yuming; Takaki, Takashi; Inaba, Muneo; Ikehara, Susumu

    2010-07-01

    Thymic function decreases in line with tumor progression in patients with cancer, resulting in immunodeficiency and a poor prognosis. In the present study, we attempted to restore thymic function by BALB/c (H-2(d)) syngeneic (Syn), or B6 (H-2(b)) allogeneic (Allo) bone marrow transplantation (BMT) using intra-bone marrow-bone marrow transplantation (IBM-BMT) plus Syn-, Allo- or C3H (H-2(k)) 3rd-party fetal thymus transplantation (TT). Although the BALB/c mice with advanced tumors (Meth-A sarcoma; H-2(d), >4 cm(2)) treated with either Syn- or Allo-BMT alone showed a slight improvement in survival compared with non-treated controls, the mice treated with BMT + TT showed a longer survival. The mice treated with Allo-BMT + Allo-TT or 3rd-party TT showed the longest survival. Interestingly, although there was no difference in main tumor size among the BMT groups, lung metastasis was significantly inhibited by Allo-BMT + Allo-TT or 3rd-party TT. Numbers of CD4(+) and CD8(+) T cells, Con A response, and IFN-gamma production increased significantly, whereas number of Gr-1(+)/CD11b(+) myeloid suppressor cells and the percentage of FoxP3(+) cells in CD4(+) T cells significantly decreased in these mice. Furthermore, there was a positive correlation between survival days and the number of T cells or T cell function, while there was a negative correlation between survival days and lung metastasis, the number of Gr-1(+)/CD11b(+) cells, or the percentage of FoxP3(+) cells. These results suggest that BMT + TT, particularly Allo-BMT + Allo-TT or 3rd-party TT, is most effective in prolonging survival as a result of the restoration of T cell function in hosts with advanced tumors.

  1. Results of the first phase I/II clinical vaccination trial with direct injection of mRNA.

    PubMed

    Weide, Benjamin; Carralot, Jean-Philippe; Reese, Anne; Scheel, Birgit; Eigentler, Thomas Kurt; Hoerr, Ingmar; Rammensee, Hans-Georg; Garbe, Claus; Pascolo, Steve

    2008-01-01

    Vaccination against tumor antigens has been shown to be a safe and efficacious prophylactic and therapeutic antitumor treatment in many animal models. Clinical studies in humans indicate that specific immunotherapy can also result in clinical benefits. The active pharmaceutical ingredient in such vaccines can be DNA, RNA, protein, or peptide and can be administered naked, encapsulated, or after delivery in vitro into cells that are then adoptively transferred. One of the easiest, most versatile and theoretically safest technologies relies on the direct injection of naked messenger RNA (mRNA) that code for tumor antigens. We and others have shown in mice that intradermal application of naked mRNA results in protein expression and the development of an immune response. We used this protocol to vaccinate 15 melanoma patients. For each patient a growing metastasis was removed, total RNA was extracted, reverse-transcribed, amplified, and cloned. Libraries of cDNA were transcribed to produce unlimited amounts of copy mRNA. Autologous preparations were applied intradermally in combination with granulocyte macrophage colony-stimulating factor as adjuvant. We demonstrate here that such treatment is feasible and safe (phase 1 criteria). Furthermore, an increase in antitumor humoral immune response was seen in some patients. However, a demonstration of clinical effectiveness of direct injection of copy mRNA for antitumor immunotherapy was not shown in this study and must be evaluated in subsequent trials.

  2. Intradermal delivery of adenoviral type-35 vectors leads to high efficiency transduction of mature, CD8+ T cell-stimulating skin-emigrated dendritic cells.

    PubMed

    de Gruijl, Tanja D; Ophorst, Olga J A E; Goudsmit, Jaap; Verhaagh, Sandra; Lougheed, Sinéad M; Radosevic, Katarina; Havenga, Menzo J E; Scheper, Rik J

    2006-08-15

    Recombinant adenovirus (Ad) type 35 (rAd35) shows great promise as vaccine carrier with the advantage of low pre-existing immunity in human populations, in contrast to the more commonly used rAd5 vector. The rAd35 vector uses CD46 as a high-affinity receptor, which, unlike the rAd5 receptor, is expressed on human dendritic cells (DC), the most powerful APCs identified to date. In this study, we show that in contrast to rAd5, rAd35 infects migrated and mature CD83+ cutaneous DC with high efficiency (up to 80%), when delivered intradermally in an established human skin explant model. The high transduction efficiency is in line with high expression levels of CD46 detected on migratory cutaneous DC, which proved to be further increased upon intradermal administration of GM-CSF and IL-4. As compared with Ad5, these Ad35 infection characteristics translate into higher absolute numbers of skin-emigrated DC per explant that both express the transgene and are phenotypically mature. Finally, we demonstrate that upon intracutaneous delivery of a rAd35 vaccine encoding the circumsporozoite (CS) protein of Plasmodium falciparum, emigrated DC functionally express and process CS-derived epitopes and are capable of activating specific CD8+ effector T cells, as evidenced by activation of an HLA-A2-restricted CS-specific CD8+ T cell clone. Collectively, these data demonstrate the utility of rAd35 vectors for efficient in vivo human DC transduction.

  3. Topical and Intradermal Efficacy of Photodynamic Therapy with Methylene Blue and Light-Emitting Diode in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis

    PubMed Central

    Sbeghen, Mônica Raquel; Voltarelli, Evandra Maria; Campois, Tácito Graminha; Kimura, Elza; Aristides, Sandra Mara Alessi; Hernandes, Luzmarina; Caetano, Wilker; Hioka, Noboru; Lonardoni, Maria Valdrinez Campana; Silveira, Thaís Gomes Verzignassi

    2015-01-01

    Introduction: The topical and intradermal photodynamic therapy (PDT) effect of methylene blue (MB) using light-emitting diode (LED) as light source (MB/LED-PDT) in the treatment of lesions of American cutaneous leishmaniasis (ACL) caused by Leishmania braziliensis in hamsters were investigated. Methods: Hamsters were infected in the footpad with 4×107 promastigotes of L. braziliensis and divided in 4 groups: Control group was not treated, AmB group was treated with amphotericin B, MB-Id group received intradermal MB at the edge of the lesion and MB-Tp group received MB topic. After treatment with MB, the animals were illuminated using red LEDs at the 655 nm wavelength for 1 hour. The MB/LED-PDT was carried out three times a week for 12 weeks. Results: Animals of MB-Tp group presented lesion healing with significant diminution in extent of the lesion, and reduced parasite burden compared to control group; however, no significant difference was seen compared to the AmB group. MB-Tp group also showed reconstitution of the epithelium, the formation of collagen fibers, organization in the epidermis, a little disorganization and inflammation in the dermis. MB-Id was ineffective in all parameters evaluated, and it was comparable to the control group results. Conclusion: These data show that PDT with the use of MB-Tp and LED may be an alternative for the treatment of ACL. However, additional studies are being conducted to assess the potential of MB/LED-PDT, alone or in combination with conventional therapy, for the treatment of ACL. PMID:26464777

  4. Assessment of the sensitivity of the gamma-interferon test and the single intradermal comparative cervical test for the diagnosis of bovine tuberculosis under field conditions.

    PubMed

    Praud, A; Boschiroli, M L; Meyer, L; Garin-Bastuji, B; Dufour, B

    2015-01-01

    In some French départements, the eradication of bovine tuberculosis is incomplete and usual skin tests [single intradermal tuberculin test (SIT) and single intradermal comparative cervical test (SICCT)] have poor specificity due to cross-reactions with non-pathogenic mycobacteria, causing economic losses. In Côte d'Or (Burgundy, France), an experimental serial testing scheme based on the combination of SICCT and gamma-interferon (IFN-γ) tests has been initiated in order to shorten the interval between suspicion and its invalidation in herds with false-positive results to skin tests. Our aim was to assess the scheme's sensitivity and to compare it to the sensitivity of the screening scheme recommended by the European Commission. Our study included 1768 animals from Côte d'Or. The sensitivities of both schemes were estimated using a Bayesian approach. The individual sensitivity of the IFN-γ test [88·1%, 95% credibility interval (CrI) 72·8-97·5] was not significantly different from individual SICCT sensitivity (80·3%, 95% CrI 61·6-98·0) and individual SIT sensitivity (84·2%, 95% CrI 59·0-98·2). The individual specificity of the IFN-γ test was 62·3% (95% CrI 60·2-64·5). No significant difference could be demonstrated between the sensitivities of the serial testing scheme used in Côte d'Or (73·1%, 95% CrI 41·1-100) and the European Union serial testing scheme (70·1%, 95% CrI 31·5-100·0).

  5. Determination of irritant threshold concentrations of multiple tree, grass, weed and mould allergens for intradermal testing of horses residing in the southern USA.

    PubMed

    Lane, Martha J; Pucheu-Haston, Cherie M; Kearney, Michael T; Woodward, Michelle

    2017-07-18

    Appropriate allergen threshold concentrations (TCs) for intradermal testing (IDT) have not been established in horses for many pollen and mould allergens. To determine the TCs in non-allergic horses and describe the frequency of late phase reactions for 26 allergens, including trees, grasses, weeds and moulds in horses residing in the southern Unites States. Twenty four clinically normal horses in the southern United States. Threshold concentrations for different allergens were determined using IDT subjective measurements at 30 minutes. Delayed reactions were evaluated at 4 and 24 h. Threshold concentrations (all PNU/mL) were established for eight tree allergens (black willow 1,000, box elder 1,000, live oak 1,000, pecan 2,000, white ash 4,000, red oak 4,000, red mulberry 2,000 and green ash 2,000); two grass allergens (Johnson grass 250 PNU/mL and Kentucky blue grass 500 PNU/mL); two weeds (carelessweed 1,000 PNU/mL, great ragweed 500 PNU/mL) and one mould (Curvularia 8,000 PNU/mL). The TC was not determined due to excessive reactivity at the lowest concentration tested (1,000 PNU/mL) for bahia and perennial rye grass. Eleven other allergens did not meet the criteria to establish a TC when evaluated at 30 min due to lack of positive reactions. Multiple allergens caused positive reactions in ≥10% of horses at 4 h. Reactions at 24 h were rare with the exception of one horse. This study identified intradermal TC for multiple pollen and mould allergens in horses. These values may prove useful for optimizing allergen concentrations for IDT of allergic horses. © 2017 ESVD and ACVD.

  6. Increasing the efficacy of antitumor glioma vaccines by photodynamic therapy and local injection of allogeneic glioma cells

    NASA Astrophysics Data System (ADS)

    Christie, Catherine E.; Peng, Qian; Madsen, Steen J.; Uzal, Francisco A.; Hirschberg, Henry

    2016-03-01

    Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage vaccines could be increased by: (1) PDT of the priming tumor cells, and (2) injection of allogeneic glioma cells directly into brain tumors. Experiments were conducted in an in vivo brain tumor model using Fisher rats and BT4C (allogeneic) and F98 (syngeneic) glioma cells. Preliminary results showed that vaccination alone had significantly less inhibitory effect on F98 tumor growth compared to the combination of vaccination and allogeneic cell (BT4C) injection.

  7. Antigen injection (image)

    MedlinePlus

    Leprosy is caused by the organism Mycobacterium leprae . The leprosy test involves injection of an antigen just under ... if your body has a current or recent leprosy infection. The injection site is labeled and examined ...

  8. Amphotericin B Liposomal Injection

    MedlinePlus

    Amphotericin B liposomal injection is used to treat fungal infections such as cryptococcal meningitis (a fungal infection of the ... infections in people who cannot receive conventional amphotericin B therapy. Amphotericin B liposomal injection is in a ...

  9. Calcitonin Salmon Injection

    MedlinePlus

    Calcitonin salmon injection is used to treat osteoporosis in postmenopausal women. Osteoporosis is a disease that causes bones to weaken and break more easily. Calcitonin salmon injection is also used to treat Paget's disease ...

  10. Deoxycholic Acid Injection

    MedlinePlus

    Deoxycholic acid injection is used to improve the appearance and profile of moderate to severe submental fat ('double chin'; fatty tissue located under the chin). Deoxycholic acid injection is in a class of medications called ...

  11. Aminocaproic Acid Injection

    MedlinePlus

    Aminocaproic acid injection is used to control bleeding that occurs when blood clots are broken down too quickly. This ... the baby is ready to be born). Aminocaproic acid injection is also used to control bleeding in ...

  12. Collagenase Clostridium Histolyticum Injection

    MedlinePlus

    Collagenase Clostridium histolyticum injection is used to treat Dupuytren's contracture (a painless thickening and tightening of tissue [cord] beneath ... of tissue can be felt upon examination. Collagenase Clostridium histolyticum injection is also used to treat Peyronie's ...

  13. Brentuximab Vedotin Injection

    MedlinePlus

    ... healthy bone marrow) or at least two treatment periods of chemotherapy. Brentuximab vedotin injection is also used ... lymphoma) who did not respond to another treatment period of chemotherapy. Brentuximab vedotin injection is in a ...

  14. Sodium Ferric Gluconate Injection

    MedlinePlus

    Sodium ferric gluconate injection is used to treat iron-deficiency anemia (a lower than normal number of ... are also receiving the medication epoetin (Epogen, Procrit). Sodium ferric gluconate injection is in a class of ...

  15. OnabotulinumtoxinA Injection

    MedlinePlus

    Botox® Cosmetic ... OnabotulinumtoxinA injection (Botox, Botox Cosmetic) is used to treat a number of conditions.OnabotulinumtoxinA injection (Botox) is used to relieve the symptoms of cervical dystonia ( ...

  16. Slit injection device

    DOEpatents

    Alger, Terry W.; Schlitt, Leland G.; Bradley, Laird P.

    1976-06-15

    A laser cavity electron beam injection device provided with a single elongated slit window for passing a suitably shaped electron beam and means for varying the current density of the injected electron beam.

  17. Urinary incontinence - injectable implant

    MedlinePlus

    Intrinsic sphincter deficiency repair; ISD repair; Injectable bulking agents for stress urinary incontinence ... Urine leakage that gets worse Pain where the injection was done Allergic reaction to the material Implant ...

  18. Hip joint injection

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007633.htm Hip joint injection To use the sharing features on this ... injection is a shot of medicine into the hip joint. The medicine helps relieve pain and inflammation. It ...

  19. Sensitization or tolerance to Mycobacterium leprae antigen by route of injection.

    PubMed Central

    Shepard, C C; Walker, L L; Van Landingham, R M; Ye, S Z

    1982-01-01

    Aqueous suspensions of heat-killed Mycobacterium leprae in a dose of 10(7) organisms were highly immunogenic when injected intradermally (i.d.). The same dose of bacteria did not sensitize when given intraperitoneally (i.p.) or intravenously (i.v.), and did so only minimally at best when given subcutaneously. The i.d. route was the most immunogenic for sheep erythrocytes also. M. leprae injected i.p. or i.v. stimulated immune tolerance to M. leprae challenge i.d. In older mice (greater than or equal to 8 weeks), the i.v. injections gave more complete tolerance. Mice that had been rendered tolerant by i.v. injections maintained their tolerance for at least 168 days. Prior UV irradiation of intact mice prevented sensitization by the i.d. route. In normal mice, living M. bovis BCG given i.d. produced good sensitization to M. leprae. Mice that had been made tolerant by i.v. injection of M. leprae could be partially sensitized to M. leprae by i.d. immunization with BCG; mixtures of living BCG and heat-killed M. leprae were no more effective than BCG alone. These findings appear to have relevance to the pathogenesis of lepromatous leprosy and its immunoprophylaxis. PMID:6754621

  20. Sensitization or tolerance to Mycobacterium leprae antigen by route of injection

    SciTech Connect

    Shepard, C.C.; Walker, L.L.; Van Landingham, R.M.; Ye, S.Z.

    1982-11-01

    Aqueous suspensions of heat-killed Mycobacterium leprae in a dose of 10(7) organisms were highly immunogenic when injected intradermally (i.d.). The same dose of bacteria did not sensitize when given intraperitoneally (i.p.) or intravenously (i.v.), and did so only minimally at best when given subcutaneously. The i.d. route was the most immunogenic for sheep erythrocytes also. M. leprae injected i.p. or i.v. stimulated immune tolerance to M. leprae challenge i.d. In older mice (greater than or equal to 8 weeks), the i.v. injections gave more complete tolerance. Mice that had been rendered tolerant by i.v. injections maintained their tolerance for at least 168 days. Prior UV irradiation of intact mice prevented sensitization by the i.d. route. In normal mice, living M. bovis BCG given i.d. produced good sensitization to M. leprae. Mice that had been made tolerant by i.v. injection of M. leprae could be partially sensitized to M. leprae by i.d. immunization with BCG; mixtures of living BCG and heat-killed M. leprae were no more effective than BCG alone. These findings appear to have relevance to the pathogenesis of lepromatous leprosy and its immunoprophylaxis.