Intradermal infections of mice by low numbers of african trypanosomes are controlled by innate resistance but enhance susceptibility to reinfection.

PubMed

Wei, Guojian; Bull, Harold; Zhou, Xia; Tabel, Henry

2011-02-01

Antibodies are required to control blood-stage forms of African trypanosomes in humans and animals. Here, we report that intradermal infections by low numbers of African trypanosomes are controlled by innate resistance but prime the adaptive immune response to increase susceptibility to a subsequent challenge. Mice were found 100 times more resistant to intradermal infections by Trypanosoma congolense or Trypanosoma brucei than to intraperitoneal infections. B cell-deficient and RAG2(-/-) mice are as resistant as wild-type mice to intradermal infections, whereas inducible nitric oxide synthase (iNOS)(-/-) mice and wild-type mice treated with antibody to tumor necrosis factor (TNF) α are more susceptible. We conclude that primary intradermal infections with low numbers of parasites are controlled by innate defense mediated by induced nitric oxide (NO). CD1d(-/-) and major histocompatibility complex (MHC) class II(-/-) mice are more resistant than wild-type mice to primary intradermal infections. Trypanosome-specific spleen cells, as shown by cytokine production, are primed as early as 24 h after intradermal infection. Infecting mice intradermally with low numbers of parasites, or injecting them intradermally with a trypanosomal lysate, makes mice more susceptible to an intradermal challenge. We suggest that intradermal infections with low numbers of trypanosomes or injections with trypanosomal lysates prime the adaptive immune system to suppress protective immunity to an intradermal challenge.

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

PubMed

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.

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

Safety, tolerability and efficacy of intradermal rabies immunization with DebioJect™.

PubMed

Vescovo, Paul; Rettby, Nils; Ramaniraka, Nirinarilala; Liberman, Julie; Hart, Karen; Cachemaille, Astrid; Piveteau, Laurent-Dominique; Zanoni, Reto; Bart, Pierre-Alexandre; Pantaleo, Giuseppe

2017-03-27

In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Effect of intradermal tuberculin tests on BCG-induced allergy

PubMed Central

Magnus, Knut

1957-01-01

Trials are going forward to determine whether intradermal tuberculin testing with 10 TU at yearly intervals after BCG vaccination may prevent waning of BCG-induced allergy in schoolchildren. Meanwhile, two experiments to the same purpose, carried out in guinea-pigs, are described. They show that waning allergy in guinea-pigs can be sustantially enhanced by intradermal injection of either purified tuberculin or Old Tuberculin, the effect lasting for at least 8 weeks, even with so small a dose as 5 TU. It is pointed out that this enhancing effect has been demonstrated only in BCG-vaccinated guinea-pigs and that it is not known whether the same phenomenon would occur in guinea-pigs infected with living human tubercle bacilli. PMID:13489466

Effect of tape stripping and adjuvants on immune response after intradermal DNA electroporation.

PubMed

Vandermeulen, Gaëlle; Daugimont, Liévin; Richiardi, Hervé; Vanderhaeghen, Marie-Lise; Lecouturier, Nathalie; Ucakar, Bernard; Préat, Véronique

2009-07-01

DNA vaccines require both efficient delivery methods and appropriate adjuvants. Based on their mechanisms of action, we hypothesised that some adjuvants could enhance vaccine immunogenicity or direct the response towards Th1 profile after intradermal DNA electroporation. After intradermal electroporation of plasmid DNA encoding luciferase, mice received hyaluronidase, imiquimod, monophosphoryl lipid A or were tape stripped in order to modulate the immune response against the encoded protein. We measured total immunoglobulin G, IgG1, IgG2a titres and the cytokines produced by splenocyte cultures to assess both humoral and cellular response. The effect of tape stripping on the response against intradermally delivered ovalbumin protein was also assessed. Neither hyaluronidase nor imiquimod improved the immune response against the encoded luciferase. Monophosphoryl lipid A did not modify the cytokines production but increased the anti-luciferase IgG2a titres. Tape stripping significantly increased anti-luciferase IgG2a and IFN-gamma responses. It also enhanced the humoral response after intradermal injection of the ovalbumin protein. Tape stripping is able to increase the Th1 immune response against both DNA and protein vaccines. Therefore, tape stripping appears to have interesting adjuvant effect on intradermal vaccination.

Fluzone® Intradermal Quadrivalent Influenza Vaccine.

PubMed

Robertson, Corwin A; Tsang, Peter; Landolfi, Victoria A; Greenberg, David P

2016-10-01

An intradermal version of Fluzone® split-virion inactivated trivalent influenza vaccine, containing 9 µg hemagglutinin per strain of A/H1N1, A/H3N2, and one B lineage virus (Fluzone Intradermal, Sanofi Pasteur), became available in the US during the 2011-2012 influenza season for adults 18-64 years of age. In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9 µg hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata). This literature review summarizes the history and mechanism of intradermal vaccination, discusses the clinical trial results supporting the immunogenicity and safety of Fluzone Intradermal Quadrivalent vaccine, and describes the unique microinjection system used to deliver Fluzone Intradermal Quadrivalent. Expert commentary: Fluzone Intradermal Quadrivalent may boost confidence in influenza vaccination with the addition of a second B-lineage strain. By using an innovative microinjection system, the vaccine is also designed to address some of the logistic challenges faced by healthcare providers administering immunizations.

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.

Effect of intradermal human recombinant copper-zinc superoxide dismutase on random pattern flaps in rats.

PubMed

Schein, Ophir; Westreich, Melvyn; Shalom, Avshalom

2013-09-01

Studies have focused on enhancing flap viability using superoxide dismutase (SOD), but only a few used SOD from human origin, and most gave the compound systemically. We evaluated the ability of SOD to improve random skin flap survival using human recombinant copper-zinc superoxide dismutase (Hr-CuZnSOD) in variable doses, injected intradermally into the flap. Seventy male Sprague Dawley rats were randomly assigned into 4 groups. Cephalic random pattern flaps were elevated on their backs and intradermal injections of different dosages of Hr-CuZnSOD were given 15 minutes before surgery. Flap survival was evaluated by fluorescein fluorescence. Analysis of variance (ANOVA) and t test statistical analyses were performed. Flap survival in all treated groups was significantly better than in the controls. The beneficial effect of HR-CuZnSOD on flap survival is attained when it is given intradermally into the flap tissue. Theoretically, Hr-CuZnSOD delivered with local anesthetics used in flap elevation may be a valuable clinical tool. Copyright © 2012 Wiley Periodicals, Inc.

Evaluation of the use of a needle-free injection syringe as a cause of non-specific reactions in the intradermal tuberculin test used for the diagnosis of bovine tuberculosis.

PubMed

Díez-Guerrier, A; Roy, A; de la Cruz, M L; Sáez, J L; Sanz, C; Boschiroli, M L; Romero, B; de Juan, L; Domínguez, L; Bezos, J

2018-05-24

The objective of the study was to elucidate whether the use of the needle-free Dermojet syringe, which is based on a high pressure inoculation and is used to inject tuberculin in cattle in several countries, may, in itself, cause skin reactions that can be interpreted as positive reactions to the intradermal tests that are not, in fact, related to the real infection status of the animals. Forty-four cattle from an officially tuberculosis-free (OTF) herd were selected, and four single intradermal tuberculin (SIT) tests were performed on each animal, two on each side of the neck. Three different Dermojet (D1, D2 and D3) and one McLintock (M4) syringes were used to carry out sterile phosphate buffer saline (PBS) with 10% of glycerol and bovine PPD injections. No positive reactions to the SIT test were observed when using the D1-D3 syringes in the case of either bovine PPD or PBS. With regard to M4 (PBS), all the tests were negative when using a standard interpretation but three were positive in the case of the severe interpretation. Significant differences (p < 0.05) in the skin fold thickness measured were found only between certain Dermojet and McLintock syringes at certain inoculation sites. The results showed that the needle-free Dermojet syringe used for PPD intradermal testing in cattle did not cause significant reactions that could be misunderstood as positives. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

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.

A potential relationship between skin hydration and stamp-type microneedle intradermal hyaluronic acid injection in middle-aged male face.

PubMed

Seok, Joon; Hong, Ji Yeon; Choi, Sun Young; Park, Kui Young; Kim, Beom Joon

2016-12-01

There is an increasing interest in skin rejuvenation using hyaluronic acid (HA) fillers beyond the improvement of deep wrinkles and volume deficiencies, which have been primary research foci in the past. We conducted a pilot study using a sample of six middle-aged male subjects. Using an automatic intradermal injector with 0.020 mL of material contained in each injection point with a total of 100 points, 2 mL of non-cross-HA filler was injected into the entire face at every treatment session. We administered injections of HA for a total of three sessions per subject at 2-week intervals and evaluated the results using a corneometer, TEWL, cutometer, measures of patient satisfaction, and the global aesthetic improvement scale (GAIS). Corneometer values increased steadily at each measurement, while the average value of TEWL increased in comparison with baseline after each application of the procedure. However, values returned to readings similar to those at 4 weeks after complete termination of the procedures. Cutometer values differed between the baseline and after procedures. All patients were assessed as "very much improved" or "much improved" according to GAIS, and all were pleased with the outcomes of treatment in terms of the enhancement of moisture, elasticity, and brightness. © 2016 Wiley Periodicals, Inc.

Enhanced immunity in intradermal vaccination by novel hollow microneedles.

PubMed

Ogai, N; Nonaka, I; Toda, Y; Ono, T; Minegishi, S; Inou, A; Hachiya, M; Fukamizu, H

2018-04-29

The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity. We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses. The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge-shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination. The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice.

PubMed

Yang, Shi-feng; Xue, Wu-jun; Lu, Wan-hong; Xie, Li-yi; Yin, Ai-ping; Zheng, Jin; Sun, Ji-ping; Li, Yang

2015-10-01

Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT. Copyright © 2015 Elsevier B.V. All rights reserved.

Importance of beta 2-adrenoceptor stimulation in the suppression of intradermal antigen challenge by adrenaline.

PubMed Central

Warren, J B; Pixley, F J; Dollery, C T

1989-01-01

1. Seven atopic subjects received two injections of antigen and one of saline intradermally in the back on each of 4 separate days. They were pretreated with four different drug combinations: (a) adrenaline 0.3 mg subcutaneously over the deltoid muscle (b) subcutaneous adrenaline preceded by 5 mg of the specific beta 2-adrenoceptor antagonist ICI 118,551 orally (c) 8 mg of salbutamol orally (d) placebo. Tablets were given 2 h before and subcutaneous injections 15 min before the intradermal injections of saline and antigen. 2. The median flare response to intradermal low dose antigen and high dose antigen after pretreatment with adrenaline was 4% and 49% of the response seen following pretreatment with placebo (P less than 0.001). When adrenaline was preceded by ICI-118,551, the corresponding median flare responses were 2% and 44% (P less than 0.001) of the placebo response. The flare response after pretreatment with salbutamol was not significantly different from placebo. 3. Adrenaline suppressed the median weal response to the higher dose of antigen to 52% of the response after pretreatment with placebo (P less than 0.05). This suppression by adrenaline was blocked by pretreatment with ICI 118,551. The median weal response after the highest dose of antigen was suppressed by salbutamol to 66% of the response seen after placebo, although this was not significant even when a further three subjects were studied with either salbutamol or placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2565729

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.

Laser Doppler imager (LDI) scanner and intradermal injection for in vivo pharmacology in human skin microcirculation: responses to acetylcholine, endothelin-1 and their repeatability

PubMed Central

Saez, Anabelle M Opazo; Mosel, Frank; Nürnberger, Jens; Rushentsova, U; Gössl, Mario; Mitchell, Anna; Schäfers, Rafael F; Philipp, Thomas; Wenzel, René R

2005-01-01

Aims The purpose of this study was to evaluate the repeatability of forearm skin blood flow responses to intradermal injections of acetylcholine (ACh) and endothelin-1 (ET-1) using a double injection technique (DIT) and a laser Doppler imager (LDI) scanner in the human skin microcirculation. Methods We used a laser Doppler imager (Moor LDI V3.01) to continuously monitor the change in skin blood flow during intradermal administration of physiological saline (0.9% NaCl), acetylcholine (ACh 10−7, 10−8, 10−9 M) and endothelin-1 (ET-1 10−14, 10−16, 10−18 M) in 10 healthy male subjects. Subjects were examined on 3 different days for assessment of interday and interobserver repeatability. Injections of either drug were randomly placed on different sites of the forearm. Laser Doppler images were collected before and after injection at 2.5 min intervals for 30 min. Data were analysed after the completion of each experiment using Moor Software V.3.01. Results are expressed as changes from baseline in arbitrary perfusion units (PU). Results ACh caused a significant vasodilation (P< 0.0001 anova, mean ± SE: 766 ± 152 PU, ACh 10−9 M; 1868 ± 360 PU, ACh 10−8 M; 4188 ± 848 PU, ACh 10−7 M; mean of days 1 and 2, n = 10), and ET-1 induced a significant vasoconstrictive response (P< 0.0001 anova, −421 ± 83 PU, ET-1 10−18 M; −553 ± 66 PU, ET-1 10−16 M; −936 ± 90 PU, ET-1 10−14 M; mean of days 1 and 2, n = 10). There was no difference on the response to either drug on repeated days. Bland-Altman analyses showed a close agreement of responses between days with repeatability coefficients of 1625.4 PU for ACh, and 386.0 PU for ET-1 (95% CI: ACh, −1438 to 1747 PU, ET-1, −399 to 358 PU) and between observers with repeatability coefficients of 1057.2 PU for ACh and 255.8 PU for ET-1 (95% CI: ACh, −1024 to 1048 PU, ET-1, −252 to 249 PU). The variability between these responses was independent of average flux values for both ACh and ET-1. There was

Intradermal injection of an anti-Langerin-HIVGag fusion vaccine targets epidermal Langerhans cells in nonhuman primates and can be tracked in vivo.

PubMed

Salabert, Nina; Todorova, Biliana; Martinon, Frédéric; Boisgard, Raphaël; Zurawski, Gerard; Zurawski, Sandra; Dereuddre-Bosquet, Nathalie; Cosma, Antonio; Kortulewski, Thierry; Banchereau, Jacques; Levy, Yves; Le Grand, Roger; Chapon, Catherine

2016-03-01

The development of new immunization strategies requires a better understanding of early molecular and cellular events occurring at the site of injection. The skin is particularly rich in immune cells and represents an attractive site for vaccine administration. Here, we specifically targeted vaccine antigens to epidermal Langerhans cells (LCs) using a fusion protein composed of HIV antigens and a monoclonal antibody targeting Langerin. We developed a fluorescence imaging approach to visualize, in vivo, the vaccine-targeted cells. Studies were performed in nonhuman primates (NHPs) because of their relevance as a model to assess human vaccines. We directly demonstrated that in NHPs, intradermally injected anti-Langerin-HIVGag specifically targets epidermal LCs and induces rapid changes in the LC network, including LC activation and migration out of the epidermis. Vaccine targeting of LCs significantly improved anti-HIV immune response without requirement of an adjuvant. Although the co-injection of the TLR-7/8 synthetic ligand, R-848 (resiquimod), with the vaccine, did not enhance significantly the antibody response, it stimulated recruitment of HLA-DR+ inflammatory cells to the site of immunization. This study allowed us to characterize the dynamics of early local events following the injection of a vaccine-targeted epidermal LCs and R-848. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immunogenicity of diphtheria toxoid and poly(I:C) loaded cationic liposomes after hollow microneedle-mediated intradermal injection in mice.

PubMed

Du, Guangsheng; Leone, Mara; Romeijn, Stefan; Kersten, Gideon; Jiskoot, Wim; Bouwstra, Joke A

2018-06-02

In this study, we aimed to investigate the immunogenicity of cationic liposomes loaded with diphtheria toxoid (DT) and poly(I:C) after hollow microneedle-mediated intradermal vaccination in mice. The following liposomal formulations were studied: DT loaded liposomes, a mixture of free DT and poly(I:C)-loaded liposomes, a mixture of DT-loaded liposomes and free poly(I:C), and liposomal formulations with DT and poly(I:C) either individually or co-encapsulated in the liposomes. Reference groups were DT solution adjuvanted with or without poly(I:C) (DT/poly(I:C)). The liposomal formulations were characterized in terms of particle size, zeta potential, loading and release of DT and poly(I:C). After intradermal injection of BALB/c mice with the formulations through a hollow microneedle, the immunogenicity was assessed by DT-specific ELISAs. All formulations induced similar total IgG and IgG1 titers. However, all the liposomal groups containing both DT and poly(I:C) showed enhanced IgG2a titers compared to DT/poly(I:C) solution, indicating that the immune response was skewed towards a Th1 direction. This enhancement was similar for all liposomal groups that contain both DT and poly(I:C) in the formulations. Our results reveal that a mixture of DT encapsulated liposomes and poly(I:C) encapsulated liposomes have a similar effect on the antibody responses as DT and poly(I:C) co-encapsulated liposomes. These findings may have implications for future design of liposomal vaccine delivery systems. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

PubMed Central

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2015-01-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. PMID:25391313

Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.

PubMed

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2015-05-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Comparative safety and efficacy of subcutaneous and intradermal administration of inactivated Japanese encephalitis vaccine during predeployment preparations in the Australian Defence Force.

PubMed

Kitchener, Scott; Nasveld, Peter; Brennan, Len; Ward, David

2006-12-01

Japanese encephalitis is a viral disease emerging in areas of influence for the Australian Defence Force immediately north of the continent, including the Torres Strait border of Australia and Papua, New Guinea. Only the mouse brain-derived, inactivated, Nakayama strain vaccine is commercially available to the Australian Defence Force. This vaccine has a high cost and significant adverse event profile, requiring restricted duties after administration. To address these issues, intradermal vaccination (either single intradermal administration or two intradermal injections at two separate sites) was assessed, compared with the conventional subcutaneous vaccination method, in a randomized controlled trial among soldiers preparing for deployment. Dual intradermal vaccination (0.1 mL at two sites) was found to have a slightly more favorable adverse event profile while maintaining comparable serological efficacy and reduced cost. An expansion of the concept and a test of logistics were conducted by vaccinating a battalion formation during predeployment medical preparations. The method of vaccination was well accepted and retained comparable immunogenicity.

Intradermal capsaicin as a neuropathic pain model in patients with unilateral sciatica

PubMed Central

Aykanat, Verna; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond; Yap, Sharon; Rolan, Paul

2012-01-01

AIM This study compared the responses between patients with unilateral sciatica and pain-free volunteers following administration of intradermal capsaicin. METHODS Fourteen patients with unilateral sciatica and 12 pain-free volunteers received one injection per hour over 4 h of 1 µg and 10 µg capsaicin, into each calf. For each dose, spontaneous pain (10 cm VAS), area of flare (cm2) and the sum of allodynia and hyperalgesia radii across eight axes (cm) were recorded pre-injection and at 5, 15, 30, 45 and 60 min post injection. RESULTS Sciatica subjects experienced higher spontaneous pain and hyperalgesia responses in both legs compared with pain-free volunteers. The largest mean difference in spontaneous pain was 2.8 cm (95% CI 1.6, 3.9) at 5 min in the unaffected leg following 10 µg. The largest mean difference in hyperalgesia was 19.7 cm (95% CI 12.4, 27.0) at 60 min in the unaffected leg following 10 µg. Allodynia was greater in patients than in controls with the largest mean difference of 2.9 cm (95% CI 1, 4.8) at 5 min following 10 µg in the affected leg. Allodynia was also higher in the affected leg compared with the unaffected leg in sciatica patients with the highest mean difference of 3.0 cm (95% CI 1.2, 4.7) at 5 min following 10 µg. CONCLUSIONS The responses to intradermal capsaicin are quantitatively and qualitatively different in unilateral sciatica patients compared with pain-free controls. PMID:21740458

Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans

PubMed Central

Ushida, Takahiro; Iwatsu, Osamu; Shimo, Kazuhiro; Tetsunaga, Tomoko; Ikeuchi, Masahiko; Ikemoto, Tatsunori; Arai, Young-Chang P; Suetomi, Katsutoshi; Nishihara, Makoto

2009-01-01

Background Although magnesium ions (Mg2+) are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+). To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short), tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia. PMID:19715604

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

Syngeneic Schwann cell transplantation preserves vision in RCS rat without immunosuppression.

PubMed

McGill, Trevor J; Lund, Raymond D; Douglas, Robert M; Wang, Shaomei; Lu, Bin; Silver, Byron D; Secretan, Matt R; Arthur, Jennifer N; Prusky, Glen T

2007-04-01

To evaluate the efficacy of immunologically compatible Schwann cells transplanted without immunosuppression in the RCS rat retina to preserve vision. Syngeneic (dystrophic RCS) Schwann cells harvested from sciatic nerves were cultured and transplanted into one eye of dystrophic RCS rats at an early stage of retinal degeneration. Allogeneic (Long-Evans) Schwann cells and unoperated eyes served as controls. Vision through transplanted and unoperated eyes was then quantified using two visual behavior tasks, one measuring the spatial frequency and contrast sensitivity thresholds of the optokinetic response (OKR) and the other measuring grating acuity in a perception task. Spatial frequency thresholds measured through syngeneically transplanted eyes maintained near normal spatial frequency sensitivity for approximately 30 weeks, whereas thresholds through control eyes deteriorated to less than 20% of normal over the same period. Contrast sensitivity was preserved through syngeneically transplanted eyes better than through allogeneic and unoperated eyes, at all spatial frequencies. Grating acuity measured through syngeneically transplanted eyes was maintained at approximately 60% of normal, whereas acuity of allogeneically transplanted eyes was significantly lower at approximately 40% of normal. The ability of immunoprivileged Schwann cell transplants to preserve vision in RCS rats indicates that transplantation of syngeneic Schwann cells holds promise as a preventive treatment for retinal degenerative disease.

PREVALENCE OF PARACOCCIDIOIDOMYCOSIS INFECTION BY INTRADERMAL REACTION IN RURAL AREAS IN ALFENAS, MINAS GERAIS, BRAZIL

PubMed Central

Magalhães, Evandro Monteiro de Sá; Ribeiro, Carla de Fátima; Dâmaso, Carla Silva; Coelho, Luiz Felipe Leomil; Silva, Roberta Ribeiro; Ferreira, Eric Batista; Rodrigues, Maria Rita; de Camargo, Zoilo Pires; Velloso, Tânia Regina Grão; Malaquias, Luiz Cosme Cotta

2014-01-01

This study aimed to estimate the prevalence of paracoccidioidal infection by intradermal reaction (Delayed-Type Hypersensitivity, DTH) to Paracoccidioides brasiliensis in rural areas in Alfenas, Southern Minas Gerais (MG) State, Brazil, and to assess risk factors (gender, occupation, age, alcohol intake and smoking) associated with infection. We conducted a population-based cross-sectional study using intradermal tests with gp 43 paracoccidioidin in 542 participants, who were previously contacted by local health agents and so spontaneously attended the test. Participants underwent an interview by filling out a registration form with epidemiological data and were tested with an intradermal administration of 0.1 mL of paracoccidioidin in the left forearm. The test was read 48 hours after injection and was considered positive if induration was greater than or equal to 5 mm. Out of 542 participants, 46.67% were positive to the skin test. Prevalence increased in accordance with an increase of age. There was statistical significance only for males. Occupation, alcohol intake and smoking habits were not significantly associated with the risk of paracoccidioidomycosis infection. There is relevance of paracoccidioidomycosis infection in such rural areas, which suggests that further epidemiological and clinical studies on this mycosis should be done in the southern part of Minas Gerais State. PMID:25076426

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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intradermal bacteriostatic 0.9% sodium chloride containing the preservative benzyl alcohol compared with intradermal lidocaine hydrochloride 1% for attenuation of intravenous cannulation pain.

PubMed

McNelis, K A

1998-12-01

This study compared the efficacy of a common medication diluent, bacteriostatic 0.9% sodium chloride containing the preservative benzyl alcohol with lidocaine hydrochloride 1% as an intradermal pretreatment for the relief of pain associated with intravenous cannulation. Forty adult presurgical patients requiring two large bore intravenous catheters were used. They served as their own controls. The inner aspect of one forearm received the usual pretreatment, lidocaine hydrochloride 1%, and the inner aspect of the opposite arm received intradermal pretreatment with bacteriostatic 0.9% sodium chloride with the preservative benzyl alcohol. Intravenous cannulation was accomplished on the first attempt, and pain reported with cannulation was rated using a visual analogue scale (VAS). A paired t test was used to compare differences in VAS scores with the pretreatment bacteriostatic 0.9% sodium chloride containing the preservative benzyl alcohol with the pretreatment lidocaine hydrochloride 1%. Analysis of the data revealed no significant difference in the report of perceived pain of intravenous cannulation based on the intradermal pretreatment. These findings suggest that intradermal bacteriostatic 0.9% sodium chloride containing the preservative benzyl alcohol is as effective as intradermal lidocaine hydrochloride 1% in the attenuation of intravenous cannulation pain.

Low-dose intradermal and intramuscular vaccination against hepatitis B.

PubMed

Bryan, J P; Sjogren, M H; Perine, P L; Legters, L J

1992-03-01

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine (sIPV) with intradermal delivery in rats.

PubMed

Ma, Lei; Cai, Wei; Sun, Mingbo; Cun, Yina; Zhou, Jian; Liu, Jing; Hu, Wenzhu; Zhang, Xinwen; Song, Shaohui; Jiang, Shude; Liao, Guoyang

2016-12-01

The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90 th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions

Syngeneic graft-versus-host disease: a report of two cases and literature review.

PubMed

Latif, T; Pohlman, B; Kalaycio, M; Sobecks, R; Hsi, E D; Andresen, S; Bolwell, B J

2003-09-01

Rappeport et al first reported the clinical syndrome of graft-versus-host disease (GVHD) in syngeneic bone marrow transplant patients. Recently, there have been more reports of a GVHD-like syndrome in syngeneic bone marrow transplant patients (SGVHD) that may result in significant clinical morbidity. A total of 17 cases of SGVHD in syngeneic bone marrow transplant patients have been reported to date in the medical literature. The current report reviews these cases and presents two additional cases of severe SGVHD that have occurred at our institution.

The effects of intradermal and topical mitomycin C on wound healing.

PubMed

Porter, Glen T; Gadre, Swarupa A; Calhoun, Karen H

2006-07-01

To determine the effect of intradermal and topical mitomycin C (MMC) on skin wound healing. A prospective, controlled study in a rat wound model performed in an academic medical center. Intradermal and topical MMC application decreased wound integrity when compared with saline-treated animals at 1 week, 2 weeks, 1 month, and 6 months. Skin necrosis occurred in animals that received intradermal MMC. Hemotoxylin and eosin and immunohistochemical staining showed no consistent difference between treatment arms. Fibrosis and collagen deposition were reduced in MMC-treated wounds on trichrome staining. MMC-treated wounds showed decreased wound strength compared with controls. Intradermal MMC can cause skin necrosis. Histologic findings did not always correspond with clinical data. The data suggest cautious use of MMC in clinical situations when wound breaking strength is critical.

Priming with a simplified intradermal HIV-1 DNA vaccine regimen followed by boosting with recombinant HIV-1 MVA vaccine is safe and immunogenic: a phase IIa randomized clinical trial.

PubMed

Munseri, Patricia J; Kroidl, Arne; Nilsson, Charlotta; Joachim, Agricola; Geldmacher, Christof; Mann, Philipp; Moshiro, Candida; Aboud, Said; Lyamuya, Eligius; Maboko, Leonard; Missanga, Marco; Kaluwa, Bahati; Mfinanga, Sayoki; Podola, Lilly; Bauer, Asli; Godoy-Ramirez, Karina; Marovich, Mary; Moss, Bernard; Hoelscher, Michael; Gotch, Frances; Stöhr, Wolfgang; Stout, Richard; McCormack, Sheena; Wahren, Britta; Mhalu, Fred; Robb, Merlin L; Biberfeld, Gunnel; Sandström, Eric; Bakari, Muhammad

2015-01-01

Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools. In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids) compared to two "simplified" regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46. 129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups. A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA. World Health Organization International Clinical Trials Registry Platform PACTR

Immunogenicity and safety of Intanza(®)/IDflu(®) intradermal influenza vaccine in South Korean adults: a multicenter, randomized trial.

PubMed

Hoon Han, Sang; Hee Woo, Jun; Weber, Francoise; Joo Kim, Woo; Ran Peck, Kyong; Il Kim, Sang; Hwa Choi, Young; Myung Kim, June

2013-09-01

Intanza(®)/IDflu(®) (Sanofi Pasteur, Lyon, France) is an intradermal inactivated trivalent influenza vaccine developed as an alternative to intramuscular influenza vaccine. The objective of this study was to confirm the immunogenicity and safety of Intanza/IDflu in South Korean adults. In a phase IV multicenter trial, South Korean adults 18-59 y old (n = 120) and ≥ 60 y old (n = 120) were randomized 1:1 to receive a single dose of Intanza/IDflu (9 µg for 18-59 y, 15 µg for ≥ 60 y) or trivalent intramuscular vaccine (Vaxigrip(®) 15 µg, Sanofi Pasteur, Lyon, France). Blood was collected on pre-vaccination (day 0) and on day 21. Hemagglutination inhibition titers, seroprotection rates and seroconversion rates were determined on day 21. Geometric mean titers, seroprotection and seroconversion rates were similar between the intradermal and intramuscular vaccines in both age groups for all three vaccine strains (A/H1N1, A/H3N2 and B). Both vaccines met Committee for Medicinal Products for Human Use criteria for all three strains. Solicited systemic reactions of the intradermal groups were generally mild, transient, and similar to those of the intramuscular groups. Solicited injection site reactions were more frequent in the intradermal groups but were mostly mild, transient, and consisted mainly of pain, erythema, and pruritus. No treatment-related serious adverse events or other safety concerns were reported. These results confirm that Intanza/IDflu is an effective and well-tolerated alternative to IM influenza vaccination. (Clinicaltrials.gov NCT ID: NCT01215669).

Reactions to prick and intradermal skin tests.

PubMed

Bagg, Andrew; Chacko, Thomas; Lockey, Richard

2009-05-01

Allergy skin testing is a common procedure for the diagnosis of atopic diseases with a small risk of systemic reactions. To determine the 12-month incidence of systemic reactions (SRs) to skin prick testing (SPT) and intradermal skin testing (ST) and the symptoms and response to immediate treatment with epinephrine intramuscularly. A prospective study was conducted to evaluate SRs from ST in 1,456 patients. A standard form was used to record symptoms, signs, and treatment. The SRs are defined as any sign or symptom other than a local reaction thought to be secondary to ST. No vasovagal reactions were included. Nurses, as instructed by attending physicians, administered epinephrine (0.2 mL of a 1:1,000 dilution) intramuscularly in the deltoid as soon as any remote signs or symptoms occurred. Fifty-two patients (3.6%) had SRs (6 SPT and 46 intradermal): 43 (83%) were female, and 17 (33%) had asthma. Systemic symptoms included (SPT/intradermal) pruritic eyes, nose, or pharynx (0%/46%); worsening cough (50%/26%); sensation of difficulty swallowing (0%/20%); worsening nasal congestion (17%/15%); rhinorrhea (17%/13%); chest tightness or shortness of breath (33%/11%); generalized pruritus (17%/11%); sneezing (33%/9%); wheeze (0%/4%); and urticaria (17%/2%). No severe asthma, shock, hypotension, unconsciousness, or biphasic reactions occurred. All 52 patients received epinephrine intramuscularly, 48 (92%) oral prednisone, 9 (17%) oral prednisone to take 6 to 8 hours after a reaction, 50 (96%) oral antihistamine, and 6 (12%) nebulized beta-agonist. Of patients who underwent ST, SRs occurred in 3.6% (0.4% for SPT and 3.2% for intradermal ST), all of whom readily responded to epinephrine intramuscularly in the deltoid. This immediate administration of epinephrine seems to prevent more serious and biphasic reactions.

Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial.

PubMed

Viegas, Edna Omar; Tembe, Nelson; Nilsson, Charlotta; Meggi, Bindiya; Maueia, Cremildo; Augusto, Orvalho; Stout, Richard; Scarlatti, Gabriella; Ferrari, Guido; Earl, Patricia L; Wahren, Britta; Andersson, Sören; Robb, Merlin L; Osman, Nafissa; Biberfeld, Gunnel; Jani, Ilesh; Sandström, Eric

2017-11-27

We assessed the safety and immunogenicity of HIV-DNA priming using Zetajet™, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 μg (n = 10; 2 × 0.1 ml) or 1,200 μg (n = 10; 2 × 0.2 ml) of HIV-DNA (3 mg/ml), followed by two boosts of 10 8 pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Envelope (Env). After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher dose group (median 420 vs. 157.5 SFC/million peripheral blood mononuclear cell, p = .014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 ml using Zetajet was safe and well tolerated. Priming with the 1,200 μg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.

Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array

PubMed Central

Burton, Scott A.; Ng, Chin-Yee; Simmers, Ryan; Moeckly, Craig; Brandwein, David; Gilbert, Tom; Johnson, Nathan; Brown, Ken; Alston, Tesha; Prochnow, Gayatri; Siebenaler, Kris

2010-01-01

ABSTRACT Purpose The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application. Methods 3M’s hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability. Results Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations. Conclusions 3M’s hMTS can provide rapid, intradermal delivery of 300–1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery. PMID:20582455

Pharmacokinetic Model of the Transport of Fast-Acting Insulin From the Subcutaneous and Intradermal Spaces to Blood.

PubMed

Lv, Dayu; Kulkarni, Sandip D; Chan, Alice; Keith, Stephen; Pettis, Ron; Kovatchev, Boris P; Farhi, Leon S; Breton, Marc D

2015-07-01

Pharmacokinetic (PK) models describing the transport of insulin from the injection site to blood assist clinical decision making and are part of in silico platforms for developing and testing of insulin delivery strategies for treatment of patients with diabetes. The ability of these models to accurately describe all facets of the in vivo insulin transport is therefore critical for their application. Here, we propose a new model of fast-acting insulin analogs transport from the subcutaneous and intradermal spaces to blood that can accommodate clinically observed biphasic appearance and delayed clearance of injected insulin, 2 phenomena that are not captured by existing PK models. To develop the model we compare 9 insulin transport PK models which describe hypothetical insulin delivery pathways potentially capable of approximating biphasic appearance of exogenous insulin. The models are tested with respect to their ability to describe clinical data from 10 healthy volunteers which received 1 subcutaneous and 2 intradermal insulin injections on 3 different occasions. The optimal model, selected based on information and posterior identifiability criteria, assumes that insulin is delivered at the administrative site and is then transported to the bloodstream via 2 independent routes (1) diffusion-like process to the blood and (2) combination of diffusion-like processes followed by an additional compartment before entering the blood. This optimal model accounts for biphasic appearance and delayed clearance of exogenous insulin. It agrees better with the clinical data as compared to commonly used models and is expected to improve the in silico development and testing of insulin treatment strategies, including artificial pancreas systems. © 2015 Diabetes Technology Society.

Clinical evaluation of a novel microneedle device for intradermal delivery of an influenza vaccine: are all delivery methods the same?

PubMed

Levin, Yotam; Kochba, Efrat; Kenney, Richard

2014-07-23

The skin provides the largest immune barrier to infection and is a readily accessible site for vaccination, although intradermal (ID) injection can be challenging. The MicronJet™ microneedle is a novel device that consistently injects antigens very close to the skin's dendritic cells. A dose-sparing ID injection study was conducted in 280 healthy adult volunteers using trivalent virosomal adjuvanted influenza vaccine. ID injection of 3 μg using the MicronJet™ was well tolerated and showed a statistically higher geometric mean fold rise than the same dose ID using a conventional needle (Mantoux technique) for the H1N1 and B strains or a 15 μg intramuscular (IM) injection for the H3N2 strain. Thus, the immune response appears to partially depend on the delivery device and route of injection. The MicronJet™ may allow dose-sparing, yet give a superior response in influenza vaccination and warrants further clinical evaluation. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Efficacy of intracutaneous methylene blue injection for moderate to severe acute thoracic herpes zoster pain and prevention of postherpetic neuralgia in elderly patients].

PubMed

Cui, Ji-Zheng; Zhang, Jin-Wei; Zhang, Yun; Ma, Zheng-Liang

2016-10-20

To evaluate the clinical efficacy of intradermal injection of methylene blue for treatment of moderate to severe acute thoracic herpes zoster and prevention of postherpetica neuralgia in elderly patients. Sixty-four elderly patients with herpes zoster were randomized to receive a 10-day course of intradermal injection of methylene blue and lidocaine plus oral valaciclovir (group A, 32 cases) and intradermal injection of lidocaine plus oral valaciclovir (group B).Herpes evaluation index, pain rating index, incidence of postherpetic neuralgia, and comprehensive therapeutic effect were compared between the two groups at 11, 30 and 60 days after the treatment. The baseline characteristics were comparable between the two groups (all P>0.05). Compared with that in group B, the time for no new blister formation, blister incrustation and decrustation, and pain relief was significantly shortened in group A (P<0.05) with also obviously lower pain intensity after the treatment. The incidence of postherpetic neuralgia was significantly lower in group A than in group B at 30 days (P<0.05), but not at 60 and 90 days after the treatment. The total clinical response rate was 93.8% in group A, much higher than that in group B (62.5%, P<0.05). Intradermal injection of methylene blue can effectively shorten the disease course, reduce the pain intensity and prevent the development of postherpetic neuralgia in elderly patients with herpes zoster.

[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.

Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing

PubMed Central

1992-01-01

Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that r

Comparison of the immunogenicity and safety of the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines in the elderly.

PubMed

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

2014-07-01

The influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly. Conventional subunit (Agrippal S1; Novartis), MF59-adjuvanted (Fluad; Novartis), and intradermal (IDflu15; Sanofi Pasteur) influenza vaccines are widely used throughout South Korea. However, few comparative studies evaluating the safety and immunogenicity of these vaccines are available. Prior to the beginning of the 2011-2012 influenza season, 335 healthy elderly volunteers randomly received one of three seasonal trivalent influenza vaccines, the conventional subunit, MF59-adjuvanted, or intradermal influenza vaccine. Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination. Adverse events were recorded prospectively. A total of 113 conventional subunit, 111 MF59-adjuvanted, and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period. One month after vaccination, all three vaccines satisfied Committee for Medical Products for Human Use (CHMP) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain. Compared with the subunit vaccine, the intradermal vaccine exhibited noninferiority, while the MF59-adjuvanted vaccine exhibited superiority. Furthermore, the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination. The most common local and systemic reactions to the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines were pain at the injection site (7.1%, 10.8%, and 6.3%, respectively) and generalized myalgia (0.9%, 8.1%, and 5.4%, respectively). Local and systemic reactions were similar among the three vaccine groups. MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile. For older adults, the MF59-adjuvanted

Intradermal needle-free powdered drug injection by a helium-powered device.

PubMed

Liu, John; Hogan, N Catherine; Hunter, Ian W

2012-01-01

We present a new method for needle-free powdered drug injection via a bench-top gas-powered device. This injector provides an alternative method of vaccine delivery to address the cold chain problem--the cost and risk of transporting temperature sensitive vaccines to developing countries. The device houses interchangeable nozzle inserts to vary orifice geometries and is capable of delivering polymer beads (1-5 µm diameter) into the dermal layer of porcine tissue. Results for injection shape and injection depth versus nozzle orifice diameter demonstrate the device's controllability.

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.

Potency and Stability of Intradermal Capsaicin: Implications for Use as a Human Model of Pain in Multicenter Clinical Trials

PubMed Central

Balabathula, Pavan; Bhattacharjee, Himanshu; Thoma, Laura A; Nolly, Robert J; Horton, Frank P; Stornes, Gwendolyn D; Wan, Jim Y; Brooks, Ian M; Bachmann, Gloria A; Foster, David C; Brown, Candace S

2014-01-01

Intradermally injected capsaicin has been used extensively both as a human pain model and to assess analgesic efficacy. Factors such as dose, formulation, route, and site are known to affect its sensitivity. We determined whether potency and stability of capsaicin solutions were further sources of variability when following strict manufacturing guidelines. Capsaicin solution (1.0 mg/mL) was prepared according to Current Good Manufacturing Practice (cGMP) guidelines and aseptically filled into sterile amber borosilicate vials and stored at 5°C, 25°C, and 30°C. All samples were analyzed at one, three, six, and twelve months. Chemical stability was determined using HPLC and physical stability was evaluated by visual inspection of color changes, clarity, particulate matter, and product/ container closure abnormalities during each sampling time. Capsaicin intradermal injection was found to be sterile and retained 95% of the initial concentration for at least one year, regardless of studied storage temperatures (P<0.0001). Visual inspection indicated no changes in color, clarity, particulate matter, and product/ container closure abnormalities in all samples. These data show that capsaicin solutions (1.0 mg/mL) maintain their potency and stability over one year when manufactured according to cGMP guidelines. These results suggest that in clinical trials manufacturing of capsaicin solutions is recommended over extemporaneous compounding. PMID:25105064

Virosomal hepatitis a vaccine: comparing intradermal and subcutaneous with intramuscular administration.

PubMed

Frösner, Gert; Steffen, Robert; Herzog, Christian

2009-01-01

Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.). Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded. Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m. The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.

Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults.

PubMed

Gorse, Geoffrey J; Falsey, Ann R; Ozol-Godfrey, Ayca; Landolfi, Victoria; Tsang, Peter H

2015-02-25

An intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone(®) Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available in the US since the 2011/2012 influenza season for adults aged 18-64 years. This study examined whether adding a second B-lineage strain affects immunogenicity and safety. This randomized, double-blind, multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine (IIV4-ID) in adults 18-64 years of age in the US during the 2012-2013 influenza season. Participants were randomized 2:1:1 to receive a single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID containing the alternate B-lineage strain. Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination. 1672 participants were vaccinated with IIV4-ID, 837 with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited reactions were pain, pruritus, myalgia, headache, and malaise; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction. Antibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines

The comparative performance of the single intradermal test and the single intradermal comparative tuberculin test in Irish cattle, using tuberculin PPD combinations of differing potencies.

PubMed

Good, M; Clegg, T A; Costello, E; More, S J

2011-11-01

In national bovine tuberculosis (BTB) control programmes, testing is generally conducted using a single source of bovine purified protein derivative (PPD) tuberculin. Alternative tuberculin sources should be identified as part of a broad risk management strategy as problems of supply or quality cannot be discounted. This study was conducted to compare the impact of different potencies of a single bovine PPD tuberculin on the field performance of the single intradermal comparative tuberculin test (SICTT) and single intradermal test (SIT). Three trial potencies of bovine PPD tuberculin, as assayed in naturally infected bovines, namely, low (1192IU/dose), normal (6184IU/dose) and high (12,554IU/dose) were used. Three SICTTs (using) were conducted on 2102 animals. Test results were compared based on reactor-status and changes in skin-thickness at the bovine tuberculin injection site. There was a significant difference in the number of reactors detected using the high and low potency tuberculins. In the SICTT, high and low potency tuberculin detected 40% more and 50% fewer reactors, respectively, than normal potency tuberculin. Furthermore, use of the low potency tuberculin in the SICTT failed to detect 20% of 35 animals with visible lesions, and in the SIT 11% of the visible lesion animals would have been classified as negative. Tuberculin potency is critical to the performance of both the SICTT and SIT. Tuberculin of different potencies will affect reactor disclosure rates, confounding between-year or between-country comparisons. Independent checks of tuberculin potency are an important aspect of quality control in national BTB control programmes. Copyright © 2011 Elsevier Ltd. All rights reserved.

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. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Intradermal test reactivity to Malassezia pachydermatis in healthy basset hounds and basset hounds with Malassezia dermatitis.

PubMed

Bond, R; Patterson-Kane, J C; Lloyd, D H

2002-07-27

Nineteen healthy beagles, eight healthy basset hounds and 17 basset hounds with Malassezia dermatitis were tested intradermally with two extracts of M pachydermatis. One healthy beagle and two affected basset hounds showed wheal and flare reactions 15 minutes after the injection. Delayed reactions, consisting of erythematous macules and plaques, were commonly observed 24 hours after the injection in both the healthy and affected basset hounds, but occurred infrequently in the beagles. At 24 hours the diameters of the lesions in the healthy and affected basset hounds were significantly (P<0.01) greater than those in the healthy beagles, but the diameters in the healthy and affected basset hounds did not vary significantly. Delayed reactions in six of the basset hounds with Malassezia dermatitis were characterised histologically by superficial perivascular and periadnexal infiltrates of neutrophils and lymphocytes.

Implantation of GL261 neurospheres into C57/BL6 mice: a more reliable syngeneic graft model for research on glioma-initiating cells.

PubMed

Yi, Liang; Zhou, Chun; Wang, Bing; Chen, Tunan; Xu, Minhui; Xu, Lunshan; Feng, Hua

2013-08-01

Recent studies have demonstrated that inflammatory cells and inflammatory mediators are indispensable components of the tumor-initiating cell (TIC) niche and regulate the malignant behavior of TICs. However, conventional animal models for glioma-initiating cell (GIC) studies are based on the implantation of GICs from human glioblastoma (GBM) into immunodeficient mice without the regulation of immune system. Whether animal models can mimic the cellular microenvironment of malignancy and evaluate the biological features of GICs accurately is unclear. Here, we detected the biological features of neurosphere-like tumor cells derived from the murine GBM cell line GL261 (GL261-NS) and from primary human GBM (PGBM-NS) in vitro, injected GL261-NS into syngeneic C57/BL6 mouse brain and injected PGBM-NS into NOD/SCID mouse brain, respectively. The tumorigenic characteristics of the two different orthotopic transplantation models were analyzed and the histological discrepancy between grafts and human primary GBM was compared. We found that GICs enriched in GL261-NS, GL261-NS and PGBM-NS exhibited increased GIC potential and enhanced chemoresistance in vitro. GL261-NS was significantly more aggressive compared to GL261 adhesive cells (GL261-AC) in vivo and the enhanced aggression was more significant in syngeneic mice compared to immunodeficient mice. The discrepancy of tumorigenicity between GL261-NS and GL261-AC in C57/BL6 mice was also larger compared to that between PGBM-NS and PGBM-AC in immunodeficient mice. Syngrafts derived from GL261-NS in C57/BL6 mice corresponded to the human GBM histologically better, compared with xenografts derived from PGBM-NS in NOD/SCID mice, which lack inflammatory cells and inflammatory mediators. We conclude that the inflammatory niche is involved in the tumorigenicity of GICs and implantation of GL261-NS into C57/BL6 mice is a more reliable syngeneic graft model for in vivo study on GICs relative to the immunodeficiency model.

Physiological and behavioural effects of intradermal injection of sodium lauryl sulfate as an alternative to mulesing in lambs.

PubMed

Colditz, I G; Paull, D R; Lee, C; Fisher, A D

2010-12-01

To assess the effects on physiology and behaviour of intradermal injection of sodium lauryl sulfate (SLS) as an alternative to mulesing. Three groups of Merino lambs were studied: Control (n = 10), SLS (n = 11) and Mulesed (n = 11). The SLS group received SLS (7% w/v) and benzyl alcohol (20 mg/mL) in phosphate buffer, and the Mulesed group received 6 mL topical local anaesthetic as a wound dressing. Haematology, cortisol, beta-endorphin and haptoglobin concentrations, rectal temperatures, body weight and behaviours were monitored for up to 42 days post treatments. SLS treatment induced mild swelling followed by thin scab formation. Fever (>40°C) was observed at 12 and 24 h, cortisol concentration was elevated on days 1 and 2, haptoglobin concentration was highly elevated on days 2-7, white blood cell count was elevated on days 2 and 4 post treatment, but average daily gain was not affected. Fever at 12 h was significantly higher in the SLS than in the Mulesed group, whereas maximum temperature, temperature area under the curve (AUC), occurrence of fever, cortisol profile, cortisol AUC, white blood cell counts and haptoglobin concentrations until day 7 were comparable. The behaviours of normal standing, total standing and total lying were modified for 2 days by SLS treatment, but changes were less marked and of shorter duration than in the Mulesed group. On day 1, the SLS group spent <5% of time in total abnormal behaviours compared with 18% in the Mulesed group. The SLS group tended to spend more time in abnormal behaviours on day 1 than the Controls. The behaviour of the SLS group was similar to that of the unmulesed Controls and their physiological responses were intermediate between the Mulesed lambs receiving post-surgical analgesia and the Controls. © 2010 CSIRO. Australian Veterinary Journal © 2010 Australian Veterinary Association.

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.

Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress

PubMed Central

Wollny, Damian; Clark, Rod J.; Roopra, Avtar; Colman, Ricki J.; MacDougald, Ormond A.; Shedd, Timothy A.; Nelson, David W.; Yen, Mei-I; Yen, Chi-Liang Eric; Alexander, Caroline M.

2014-01-01

Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1−/− intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology. PMID:25101993

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.

[Experience and discussion on the national standard Standardized Manipulation of Acupuncture and Moxibustion. Part 8: Intradermal Needle].

PubMed

Luo, Ling; Yuan, Cheng-Kai; Yin, Hai-Yan; Zeng, Fang; Tang, Yong; Yu, Shu-Guang

2012-02-01

Standardized Manipulation of Acupuncture and Moxibustion Part 8: Intradermal Needle was compiled with the following principles. The compiling standard, technical features and clinic manipulations of intradermal needle were taken as the basic principle for compiling. Literature research, expert survey and clinic practice verification were applied as the drafting methods. The key issues were focused on the relationship between standardization and individualization, normalization and effectiveness, qualification and quantification. And the postural selection, reinforcing and reducing manipulations, fixing materials and embedding duration involved in intradermal needling were emphasized particularly. At the same time, details and the future way of thinking of intradermal needle were expounded in this article as well.

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.

[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

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.

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

Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis.

PubMed

Singh, Brijendra; Kasam, Rajesh K; Sontake, Vishwaraj; Wynn, Thomas A; Madala, Satish K

2017-11-01

IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.

Response of immune response genes to adjuvants poly [di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP), CpG oligodeoxynucleotide and emulsigen at intradermal injection site in pigs.

PubMed

Magiri, R B; Lai, K; Chaffey, A M; Wilson, H L; Berry, W E; Szafron, M L; Mutwiri, G K

2016-07-01

Understanding the mechanisms by which adjuvants mediate their effects provide critical information on how innate immunity influences the development of adaptive immunity. Despite being a critical vaccine component, the mechanisms by which adjuvants mediate their effects are not fully understood and this is especially true when they are used in large animals. This lack of understanding limits our ability to design effective vaccines. In the present study, we administered polyphosphazene (PCEP), CpG oligodeoxynucleotides (CpG), emulsigen or saline via an intradermal injection into pigs and assessed the impact on the expression of reported 'adjuvant response genes' over time. CpG induced a strong upregulation of the chemokine CXL10 several 'Interferon Response Genes', as well as TNFα, and IL-10, and a down-regulation of IL-17 genes. Emulsigen upregulated expression of chemokines CCL2 and CCL5, proinflammatory cytokines IL-6 and TNFα, as well as TLR9, and several IFN response genes. PCEP induced the expression of chemokine CCL2 and proinflammatory cytokine IL-6. These results suggest that emulsigen and CpG may promote recruitment of innate immune cells and Th1 type cytokine production but that PCEP may promote a Th-2 type immune response through the induction of IL-6, an inducer of B cell activity and differentiation. Copyright © 2016 Elsevier B.V. All rights reserved.

Application of water-soluble polyvinyl alcohol-based film patches on laser microporated skin facilitates intradermal macromolecule and nanoparticle delivery.

PubMed

Engelke, Laura; Winter, Gerhard; Engert, Julia

2018-07-01

The intradermal delivery of biologics has long been recognized as attractive approach for cutaneous immunotherapy, particularly vaccination. Although intradermal (i.d.) or subcutaneous (s.c.) injection provide reproducible dosing and good cost- and delivery efficiency, the major objective to avoid sharps and the need for enhanced storage stability have renewed the interest in alternative needle-free delivery strategies. This study presents a new concept for the delivery of macromolecules and nanoparticles to viable skin layers with a high density of professional antigen-presenting cells (APCs). Stable polyvinyl alcohol (PVA) polymer films as well as PVA blends with carboxymethyl cellulose (CMC) or cross-linked carbomer were prepared using an easily-scalable film casting technique. Fluorescein isothiocyanate (FITC) and rhodamine B-labeled dextrane 70 kDa (RD70), used as small and macromolecular model substances, or polystyrene (PS)-nano- and microparticles with diameters of 0.5 µm and 5 µm were directly incorporated into the polymer formulations at varying concentrations. The assembly of the polymer films with an occlusive backing tape created a film patch that provided a fast drug release upon dissolution of the water-soluble film and facilitated an intradermal drug delivery on laser microporated skin. The minimally-invasive P.L.E.A.S.E.® laser poration system (Pantec Biosolutions, Ruggell, Liechtenstein) provided access to viable skin layers by thermally ablating the superficial tissue with a pulsed Er:YAG laser (λ = 2.94 µm). In our in vitro study using excised pig skin, laser microporation induced a 4- to 5-fold increase of water transport (TEWL) through excised skin in a Franz diffusion cell compared to intact skin. The TEWL values detected were comparable to in vivo human skin. The increased water transport facilitated the dissolution of all topically applied dry PVA-based film formulations within 6 h. No dissolution of the films was seen on

Immune response and reactogenicity of intradermal administration versus subcutaneous administration of varicella-zoster virus vaccine: an exploratory, randomised, partly blinded trial.

PubMed

Beals, Chan R; Railkar, Radha A; Schaeffer, Andrea K; Levin, Yotam; Kochba, Efrat; Meyer, Brian K; Evans, Robert K; Sheldon, Eric A; Lasseter, Kenneth; Lang, Nancy; Weinberg, Adriana; Canniff, Jennifer; Levin, Myron J

2016-08-01

The licensed live, attenuated varicella-zoster virus vaccine prevents herpes zoster in adults older than 50 years. We aimed to determine whether intradermal administration of zoster vaccine could enhance vaccine immunogenicity compared with conventional needle subcutaneous administration. In this randomised, dose-ranging study, adults aged 50 years or older who had a history of varicella or who had resided in a country with endemic varicella-zoster virus infection for 30 years or more were eligible. Participants received the approved full or a 1/3 dose of zoster vaccine given subcutaneously or one of four intradermal doses (full, 1/3, 1/10, or 1/27 dose) using the MicronJet600 device. The two subcutaneous doses and the four intradermal doses were randomised (1·5:1:1:1:1:1) by computer generated sequence with randomisation stratified by age (50-59 years or 60 years or older). The primary immunogenicity endpoint was the change from baseline in IgG antibody to varicella-zoster virus-specific glycoproteins (gpELISA) measured at 6 weeks. All patients were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, number NCT01385566. Between Sept 2, 2011, and Jan 13, 2012, 224 participants were enrolled from three clinics in the USA and 223 were randomly assigned: 52 to receive the full dose subcutaneous zoster vaccine, 34 to receive the 1/3 dose subcutaneous zoster vaccine, 34 to receive the full dose intradermal zoster vaccine, 35 to receive the 1/3 dose intradermal zoster vaccine, 34 to receive the 1/10 dose intradermal zoster vaccine, and 34 to receive the 1/27 dose intradermal zoster vaccine. Full dose zoster vaccine given subcutaneously resulted in a gpELISA geometric mean fold-rise (GMFR) of 1·74 (90% CI 1·48-2·04) at 6 weeks post-vaccination compared with intradermal administration which resulted in a significantly higher gpELISA GMFR of 3·25 (2·68-3·94; p<0·0001), which also remained high at 18 months. An apparent dose

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.

Intradermally-administered influenza virus vaccine is safe and immunogenic in healthy adults 18-64 years of age.

PubMed

Gorse, Geoffrey J; Falsey, Ann R; Fling, John A; Poling, Terry L; Strout, Cynthia B; Tsang, Peter H

2013-05-01

To increase vaccine acceptance, intradermal (ID) influenza vaccine (Fluzone(®) Intradermal, Sanofi Pasteur Inc.) may be an attractive alternative to intramuscular (IM) vaccination due to smaller needle and volume injected. A multicenter, randomized (2:1 ID vs IM vaccines) study, blinded for ID vaccine lots, was conducted among 4292 adults 18-64 years of age enrolled in October 2008. Three lots of investigational trivalent influenza vaccine containing 9μg hemagglutinin (HA) per strain in 0.1mL administered ID with a 30 gauge, 1.5mm long needle were compared to standard dose vaccine (0.5mL containing 15μg HA/strain) given IM. The post-vaccination antibody geometric mean titers (GMT) for the ID vaccine were similar to the IM vaccine (H1N1: 193.2 vs. 178.3, H3N2: 246.7 vs. 230.7, and B: 102.5 vs. 126.9). Non-inferiority was met for the ID vaccine compared to IM vaccine as assessed by antibody GMT ratios (IM/ID) for all three virus strains (H1N1: 0.92, H3N2: 0.94, and B: 1.24). Seroconversion rates were non-inferior for H1N1 and H3N2, but not for B (ID vs. IM: H1N1: 61.2% vs. 60.5%, H3N2: 75.3% vs. 74.8%, and B: 46.2% vs. 54.2%). Seroprotection (HAI titer ≥1:40) rates were similar between groups (ID vs. IM, H1N1: 91.1% vs. 91.7%, H3N2: 90.7% vs. 91.4%, and B: 87.4% vs. 89.3%). Local injection site reactions overall were more common with ID than IM vaccine (ID vs. IM: 89.2% vs. 60.2%), but were usually grade 1 or 2 and transient. The frequencies of local injection site pain and systemic reactions were similar between vaccine groups, except more myalgia with IM vaccine. The ID vaccine elicited immune responses comparable to IM vaccine except for the seroconversion rate to B virus. With the exception of pain, local injection site reactions were more common with the ID vaccine, but well-tolerated and of short duration. ClinicalTrials.gov identifier: NCT00772109. Copyright © 2013 Elsevier Ltd. All rights reserved.

Injection of Syngeneic Murine Melanoma Cells to Determine Their Metastatic Potential in the Lungs.

PubMed

Timmons, Joshua J; Cohessy, Sean; Wong, Eric T

2016-05-24

Approximately 90% of human cancer deaths are linked to metastasis. Despite the prevalence and relative harm of metastasis, therapeutics for treatment or prevention are lacking. We report a method for the establishment of pulmonary metastases in mice, useful for the study of this phenomenon. Tail vein injection of B57BL/6J mice with B16-BL6 is among the most used models for melanoma metastases. Some of the circulating tumor cells establish themselves in the lungs of the mouse, creating "experimental" metastatic foci. With this model it is possible to measure the relative effects of therapeutic agents on the development of cancer metastasis. The difference in enumerated lung foci between treated and untreated mice indicates the efficacy of metastases neutralization. However, prior to the investigation of a therapeutic agent, it is necessary to determine an optimal number of injected B16-BL6 cells for the quantitative analysis of metastatic foci. Injection of too many cells may result in an overabundance of metastatic foci, impairing proper quantification and overwhelming the effects of anti-cancer therapies, while injection of too few cells will hinder the comparison between treated and controls.

Injection of Syngeneic Murine Melanoma Cells to Determine Their Metastatic Potential in the Lungs

PubMed Central

Timmons, Joshua J.; Cohessy, Sean; Wong, Eric T.

2016-01-01

Approximately 90% of human cancer deaths are linked to metastasis. Despite the prevalence and relative harm of metastasis, therapeutics for treatment or prevention are lacking. We report a method for the establishment of pulmonary metastases in mice, useful for the study of this phenomenon. Tail vein injection of B57BL/6J mice with B16-BL6 is among the most used models for melanoma metastases. Some of the circulating tumor cells establish themselves in the lungs of the mouse, creating "experimental" metastatic foci. With this model it is possible to measure the relative effects of therapeutic agents on the development of cancer metastasis. The difference in enumerated lung foci between treated and untreated mice indicates the efficacy of metastases neutralization. However, prior to the investigation of a therapeutic agent, it is necessary to determine an optimal number of injected B16-BL6 cells for the quantitative analysis of metastatic foci. Injection of too many cells may result in an overabundance of metastatic foci, impairing proper quantification and overwhelming the effects of anti-cancer therapies, while injection of too few cells will hinder the comparison between treated and controls. PMID:27285567

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

PubMed

Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W

2017-07-01

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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

Comparison of the intradermal irritant threshold concentrations of nine allergens from two different manufacturers in clinically nonallergic dogs in the USA.

PubMed

Foust-Wheatcraft, Desirae A; Dell, Darin L; Rosenkrantz, Wayne S; Griffin, Craig E

2017-12-01

The intradermal irritant threshold concentration for many allergens is unknown. To determine the intradermal irritant threshold concentration (ITC) of nine allergens from two different manufacturers. Twenty privately owned clinically nonallergic dogs. Alternaria, cat dander, Dermatophagoides farinae, Chenopodium album (lamb's quarter), Xanthium strumarium (cocklebur), Prosopis glandulosa (mesquite), Morus alba (white mulberry), Cynodon dactylon (Bermuda grass) and Phleum pretense (Timothy grass) from two manufacturers (ALK; Round Rock, TX, USA and Greer ® Laboratories; Lenoir, NC, USA) were injected intradermally at two dilutions and at 15 and 30 min evaluated subjectively (1-4) and objectively (horizontal wheal diameter) by two blinded investigators. A subjective score of 3 or 4 by either investigator at either timed reading was considered positive. If both concentrations resulted in positive reactions, two additional dilutions were performed. The ITC was defined as the lowest tested concentration that elicited a positive reaction in ≥10% of animals. The ITCs were Alternaria >2,000 PNU/mL; cat dander 750 PNU/mL (ALK) and 2,000 PNU/mL (Greer ® ); D. farinae <1:10,000 w/v; C. album <6,000 PNU/mL; X. strumarium <6,000 PNU/mL; P. glandulosa <500 PNU/mL; M. alba <6,000 PNU/mL; C. dactylon <10,000 PNU/mL (ALK) and <6,000 PNU/mL (Greer ® ); and P. pretense <6,000 PNU/mL. There were significant differences in subjective scoring and objective measurement between manufacturers for Alternaria, cat dander and P. pretense. Results revealed significant positive correlation between subjective scoring and objective measurement for each time, investigator and manufacturer separately. © 2017 ESVD and ACVD.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 relationshipmore » 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.« less

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.

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

PubMed Central

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

2015-01-01

Background. 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. Methods. 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. Results. 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. Conclusions. A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration. PMID:25567841

Ultra-long-duration local anesthesia produced by injection of lecithin-coated methoxyflurane microdroplets.

PubMed

Haynes, D H; Kirkpatrick, A F

1985-11-01

This study was designed to evaluate a new drug delivery system. The authors undertook to determine if microdroplets prepared by encapsulating volatile anesthetics with a membrane of lecithin could be used for local anesthesia. Local anesthesia was determined by monitoring the response of the rat to tail clamping and electrical stimulation of the skin following the intradermal injection of the microdroplets. Microdroplets were prepared from isoflurane, enflurane, halothane, methoxyflurane, diethyl ether, chloroform, and heptane. Although all microdroplet preparations produced local anesthesia, only methoxyflurane microdroplets produced an ultra-long duration of local anesthesia (approximately 24 h). Further characterization of the methoxyflurane microdroplets revealed two important differences from conventional local anesthetics. First, the local anesthetic effect of methoxyflurane reached a plateau that did not change significantly for 20 h while the injection of lidocaine and bupivacaine resulted in a peak effect that returned to baseline within 1 and 3 h, respectively. Second, the anesthetic effect of methoxyflurane remained essentially localized to the site of injection, while the anesthetic effect of lidocaine and bupivacaine migrated 15 cm in less than 1 h. The toxicity and safety of methoxyflurane were evaluated. When administered over the dosage range 1-16% (v/v) intradermally, or by injections into muscle, or by repeat injections every 4 days for 16 days, all animals regained their pretreatment response to painful stimulations, and there was no evidence of gross injury to tissue. Deliberate intravenous injection of 0.8 ml of 6.7% (v/v) methoxyflurane microdroplets had no apparent anesthetic or toxic effect. The present study demonstrates that methoxyflurane microdroplets produce an anesthetic effect that is highly localized, stable in intensity, ultra-long in duration, and reversible.

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

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.

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.

Intradermal Vaccination With Adjuvanted Ebola Virus Soluble Glycoprotein Subunit Vaccine by Microneedle Patches Protects Mice Against Lethal Ebola Virus Challenge.

PubMed

Liu, Ying; Ye, Ling; Lin, Fang; Gomaa, Yasmine; Flyer, David; Carrion, Ricardo; Patterson, Jean L; Prausnitz, Mark R; Smith, Gale; Glenn, Gregory; Wu, Hua; Compans, Richard W; Yang, Chinglai

2018-06-08

In this study, we investigated immune responses induced by purified Ebola virus (EBOV) soluble glycoprotein (sGP) subunit vaccines via intradermal immunization with microneedle (MN) patches in comparison with intramuscular (IM) injection in mice. Our results showed that MN delivery of EBOV sGP was superior to IM injection in eliciting higher levels and longer lasting antibody responses against EBOV sGP and GP antigens. Moreover, sGP-specific immune responses induced by MN or IM immunizations were effectively augmented by formulating sGP with a saponin-based adjuvant, and they were shown to confer complete protection of mice against lethal mouse-adapted EBOV (MA-EBOV) challenge. In comparison, mice that received sGP without adjuvant by MN or IM immunizations succumbed to lethal MA-EBOV challenge. These results show that immunization with EBOV sGP subunit vaccines with adjuvant by MN patches, which have been shown to provide improved safety and thermal stability, is a promising approach to protect against EBOV infection.

Vial usage, device dead space, vaccine wastage, and dose accuracy of intradermal delivery devices for inactivated poliovirus vaccine (IPV).

PubMed

Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin

2017-03-27

Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall

GM-CSF has disparate roles during intranasal and intradermal Francisella tularensis infection.

PubMed

Kurtz, Sherry L; Bosio, Catharine M; De Pascalis, Roberto; Elkins, Karen L

2016-12-01

Our laboratory has employed in vitro and in vivo mouse models based on Francisella tularensis Live Vaccine Strain (LVS)-induced protection to elucidate immune correlates for intracellular bacteria. Among the effectors found was GM-CSF, a pleiotropic cytokine that is integral to the development and proliferation of myeloid cells, including alveolar macrophages. GM-CSF has roles in resistance to primary murine infection with several intracellular pathogens, but its role during Francisella infection is unknown. Francisella is an intracellular pathogen that infects lungs after inhalation, primarily invading alveolar macrophages. Here we show that GM-CSF has route-dependent roles during primary infection of mice with LVS. GM-CSF deficient (GM-CSF KO) mice were slightly more susceptible than wild type to intradermal infection, but had increased resistance to intranasal infection. Similarly, these mice had increased resistance to pulmonary infection with virulent F. tularensis (SchuS4). LVS-vaccinated GM-CSF KO mice had normal adaptive immune responses, as measured by T cell activities after LVS intradermal or intranasal vaccination, and survived lethal secondary LVS challenge. GM-CSF KO mice also had robust humoral responses, producing elevated levels of serum antibodies following LVS vaccination compared to wild type mice. Taken together, our data demonstrates that the absence of GM-CSF improves resistance to pulmonary, but not intradermal, infection with Francisella. Published by Elsevier Masson SAS.

A Color-coded Imageable Syngeneic Mouse Model of Stromal-cell Recruitment by Metastatic Lymphoma.

PubMed

Matsumoto, Takuro; Suetsugu, Atsushi; Shibata, Yuhei; Nakamura, Nobuhiko; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

2015-09-01

A syngeneic color-coded imageable lymphoma model has been developed to visualize recruitment of host stromal cells by malignant lymphoma during metastasis. The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were initially established. EL4-RFP cells were subsequently injected into the tail vein of C57/BL6-GFP transgenic mice. EL4-RFP metastasis was observed in the lymph nodes of the upper mediastinum and in the liver 28 days after cell injection. Large EL4-RFP liver metastases in C57/BL6-GFP mice contained GFP-expressing stromal cells derived from the host. In addition, EL4-RFP lymphoma metastasis was formed in peri-gastric lymph nodes, which were also enriched in host GFP-expressing cells. Furthermore, EL4-RFP lymphoma cells were also observed in the peripheral blood and bone marrow of C57/BL6-GFP transgenic mice, where they were associated with GFP-expressing host cells. Lymph node, liver and bone marrow metastases were found approximately 4 weeks after transplantation and all RFP-expressing metastases were highly enriched in GFP-expressing host stromal cells. This model of malignant lymphoma can be used to study early tumor development, metastasis, and the role of the stroma, as well as for discovery and evaluation of novel therapeutics for this treatment-resistant disease. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

PubMed

Kochba, Efrat; Levin, Yotam; Raz, Itamar; Cahn, Avivit

2016-09-01

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. 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. 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]). 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.

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

Fate of bone marrow stromal cells in a syngenic model of bone formation.

PubMed

Boukhechba, Florian; Balaguer, Thierry; Bouvet-Gerbettaz, Sébastien; Michiels, Jean-François; Bouler, Jean-Michel; Carle, Georges F; Scimeca, Jean-Claude; Rochet, Nathalie

2011-09-01

Bone marrow stromal cells (BMSCs) have been demonstrated to induce bone formation when associated to osteoconductive biomaterials and implanted in vivo. Nevertheless, their role in bone reconstruction is not fully understood and rare studies have been conducted to follow their destiny after implantation in syngenic models. The aim of the present work was to use sensitive and quantitative methods to track donor and recipient cells after implantation of BMSCs in a syngenic model of ectopic bone formation. Using polymerase chain reaction (PCR) amplification of the Sex determining Region Y (Sry) gene and in situ hybridization of the Y chromosome in parallel to histological analysis, we have quantified within the implants the survival of the donor cells and the colonization by the recipient cells. The putative migration of the BMSCs in peripheral organs was also analyzed. We show here that grafted cells do not survive more than 3 weeks after implantation and might migrate in peripheral lymphoid organs. These cells are responsible for the attraction of host cells within the implants, leading to the centripetal colonization of the biomaterial by new bone.

Influenza vaccination in healthcare workers; comparison of side effects and preferred route of administration of intradermal versus intramuscular administration.

PubMed

Meijer, W J; Wensing, A M J; Bos, A A; Kuiphuis, J C F; Hagelen, E M M; Wilschut, J C; de Vries, M J T; Riezebos-Brilman, A

2017-03-13

To explore the nature and severity of side effects and future preference of intradermal versus intramuscular influenza vaccination in healthcare workers. Prospective cohort study. Two University Medical Centers in The Netherlands. Healthcare workers receiving an influenza vaccination. Healthcare workers that were vaccinated during the influenza vaccination season of 2012-2013 were approached for participation in a questionnaire study. The questionnaire was divided into two parts. The first part had to be answered directly after vaccination and the second part two weeks after vaccination. The motivation for vaccine uptake, whether or not the HCWs had direct contact with patients and the prevalence and severity of local and systemic side effects of influenza vaccination were explored. In addition, it was assessed how participants experienced the vaccination and which type of administration they preferred for future vaccination. Side effects of vaccination were more prevalent in the intradermal group versus the intramuscular group (56% versus 26%, p<0.001). Local side effects were perceived as more severe in healthcare workers receiving the intradermal vaccine. Directly after vaccination, healthcare workers preferred the intradermal vaccination. Two weeks after vaccination both types of vaccine were equally appreciated. This study shows that there are significant differences in the nature and severity of side effects upon intramuscular and intradermal influenza vaccination. This difference did not result in a preference among the vaccinated subjects for one type of vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

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. © 2013 Wiley Periodicals, Inc.

Evaluation of intradermal vaccination at the anti rabies vaccination OPD.

PubMed

Mankeshwar, R; Silvanus, V; Akarte, S

2014-09-01

Rabies is a virtually 100% fatal acute viral encephalitis caused by an RNA virus belonging to family Rhabdoviridae and genus Lyssavirus. The virus can infect all warm blooded animals. The disease is transmitted to humans by the bite, lick or scratch of an infected animal. More than 99% of all human rabies deaths occur in the developing world. It is preventable with timely and proper usage of modern immunobiologicals (vaccines and immunoglobulins). Once exposure occurs, modern prophylaxis entails immediate wound care, local infiltration of rabies immune globulin and parenteral administration of modern cell culture vaccines in multiple doses. The annual medicinal (vaccines and other drugs) cost for animal bite treatment is Rs. 2 billion approximately (2004). The objective of the present study is to evaluate the performance of the Intradermal (i.d.) route visa vis the Intramuscular (i.m.) route in our clinical setting the Antirabies Vaccination (ARV) OPD, Sir J.J. Hospital, Mumbai. A total of 1460 patients were administered the Antirabies vaccine by the Intradermal route over the 1 year period as compared to 1075 patients who were administered the Antirabies vaccine by the Intramuscular route in the previous year. 1230 (84.2) of the patients who were administered the vaccine by the i.d. route completed the schedule and 230 (15.8%) partially completed the schedule. Four hundred thirty two (40%) of the patients who were administered the vaccine by the Intramuscular route completed the schedule and 643 (59.8%) partially completed the schedule. The vaccine cost for i.d. was Rs. 2,80,600. The vaccine cost for the intramuscular (i.m.) assuming 84% compliance was estimated as Rs. 15, 64, 000. Assuming 40% compliance the cost was estimated as Rs. 7, 82, 230. Thus a saving of Rs. 5, 01, 630 to Rs. 12, 83, 400 was effected. In our setting, the Intradermal regime was cost effective and increased patient adherence and enrolment. It has now been routinely adopted at the clinic.

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

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

Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine.

PubMed

Firbas, Christa; Boehm, Thomas; Buerger, Vera; Schuller, Elisabeth; Sabarth, Nicolas; Jilma, Bernd; Klade, Christoph S

2010-03-11

An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [(3)H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-gamma) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays. More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-gamma CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema. Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.

A Phase-1 Clinical Trial of a DNA Vaccine for Venezuelan Equine Encephalitis Delivered by Intramuscular or Intradermal Electroporation

DTIC Science & Technology

2016-05-25

A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation Drew... vaccines against VEEV available in the United States. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEEV) and...groups and were vaccinated with high and low doses of pWRG/VEE or a saline placebo by intramuscular (IM) or intradermal (ID) electroporation (EP

Towards Development of a Dermal Pain Model: In Vitro Activation of Rat and Human Transient Receptor Potential Ankyrin Repeat 1 and Safe Dermal Injection of o-Chlorobenzylidene Malononitrile to Rat.

PubMed

Annas, Anita; Berg, Anna-Lena; Nyman, Eva; Meijer, Thomas; Lundgren, Viveka; Franzén, Bo; Ståhle, Lars

2015-12-01

During clinical development of analgesics, it is important to have access to pharmacologically specific human pain models. o-Chlorobenzylidene malononitrile (CS) is a selective and potent agonist of the transient receptor potential ankyrin repeat 1 (TRPA1), which is a transducer molecule in nociceptors sensing reactive chemical species. While CS has been subject to extensive toxicological investigations in animals and human beings, its effects on intradermal or subcutaneous injection have not previously been reported. We have investigated the potential of CS to be used as an agonist on TRPA1 in human experimental pain studies. A calcium influx assay was used to confirm the capacity of CS to activate TRPA1 with >100,000 times the selectivity over the transient receptor potential vanilloid receptor 1. CS dose-dependently (EC50 0.9 μM) released calcitonin gene-related peptide in rat dorsal root ganglion cultures, supporting involvement in pain signalling. In a local tolerance study, injection of a single intradermal dose of 20 mM CS to rats resulted in superficial, circular crusts at the injection sites after approximately 4 days. The histopathology evaluation revealed a mild, acute inflammatory reaction in the epidermis and dermis at the intradermal CS injection site 1 day after administration. After 14 days, the epidermal epithelium was fully restored. The symptoms were not considered to be adverse, and it is suggested that doses up to 20 μL of 20 mM CS can be safely administered to human beings. In conclusion, our data support development of a CS human dermal pain model. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

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

Intradermal vaccination for infants and children

PubMed Central

Saitoh, Akihiko; Aizawa, Yuta

2016-01-01

ABSTRACT Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children. PMID:27135736

Evaluation of a new five-injection, two-site,intradermal schedule for purified chick embryo cell rabies vaccine: A randomized, open-label, active-controlled trial in healthy adult volunteers in India.

PubMed

Sudarshan, M K; Madhusudana, S N; Mahendra, B J; Ashwath Narayana, D H; Ananda Giri, M S; Popova, O; Vakil, H B

2005-07-01

Human rabies is an ongoing significant public health problem inmany developing countries, with India reporting the highest incidence of rabies-related deaths (∼20,000 per year). Many people living in India cannot afford the standard IM postexposure prophylaxis (PEP) with cell-culture vaccines, which are administered using a 5-dose regimen developed in Essen, Germany. A potentially less expensive intradermal (ID) regimen, based on the Essen regimen, has been developed at the Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India. The objective of this study was to compare the immunogenicity and local and systemic tolerability of the KIMS-1D regimen with those of the standard Essen IM regimen in healthy adult volunteers in India. This randomized, open-label, active-controlled trial was conductedat the Antirabies Clinic, Medical College, KIMS. Healthy adult volunteers were randomly assigned to receive purified chick embryo cell vaccine (PCECV) using the KIMS-1D regimen (0.1 mL injected ID at 2 body sites on days 0, 3, 7, 14, and 28 ["2-2-2-2-2"]) or the Essen IM regimen (1 mL injected IM at 1 body site on the same days Subjects were followed up for 365 days by the treating physician and encouraged to voluntarily report any adverse events (AEs). Serum rabies virus-neutralizing antibody (RVNA) concentrations were measured before the first injection on day 0 (baseline) and on days 14, 28, 90, 180, and 365, using the rapid fluorescent focus inhibition test. Ninety-one subjects were enrolled and included in the tolerabilityand immunogenicity analyses. The ID group comprised 45 subjects (26 men, 19 women; mean [SD] age, 20.84 [1.48] years); the IM group, 46 subjects (28 men, 18 women; mean [SD] age, 21.02 [1.16] years). The most common local AEs were pain at the injection site (2/225 [0.9%] in the ID group and 10/230 [4.3%] in the IM group; P < 0.006) and itching at the injection site (5/225 [2.2%] in the ID group and none in the IM group; P = 0.026). All of

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.

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

2017-06-01

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. © 2017 John Wiley & Sons Ltd.

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

PubMed Central

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. PMID:25746201

Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation.

PubMed

Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

2017-03-01

Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation.

Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation

PubMed Central

Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

2017-01-01

Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation. PMID:28381315

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.

Muzzle imprint mark: a patterned injury which may be constituted of intradermal blood extravasations.

PubMed

Pircher, R; Bielefeld, L; Geisenberger, D; Große Perdekamp, M; Pollak, S; Thierauf-Emberger, A

2014-11-01

The muzzle imprint mark in contact shots is usually regarded as a patterned pressure abrasion depicting the barrel end as well as adjacent constructional components of the weapon. Due to parching after exposure to air, the affected skin assumes a brown color, especially along the contours of the impacting structures. Apart from this well-known type of epidermal damage, the imprint mark may also be formed by intradermal hemorrhages. In some cases, these intracutaneous bleedings manifest themselves as circular, curved or straight reddish lines mirroring the surface relief of the weapon's muzzle end. To estimate the frequency of skin hematomas in muzzle imprints, 35 consecutive contact shots to the head (temple, forehead, submental and occipital region) were evaluated. In 3 cases, the muzzle imprint mark exclusively consisted of intracutaneous bruises surrounding the bullet entrance hole. In 14 cases, the muzzle imprint was composed of both excoriations and intradermal hematomas. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steel, Jason C.; Morrison, Brian J.; Mannan, Poonam

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 studymore » 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.« less

Transgenic mice that accept Luciferase- or GFP-expressing syngeneic tumor cells at high efficiencies.

PubMed

Aoyama, Naoki; Miyoshi, Hiroyuki; Miyachi, Hitoshi; Sonoshita, Masahiro; Okabe, Masaru; Taketo, Makoto Mark

2018-05-11

Jellyfish green fluorescent protein (GFP) and firefly luciferase can serve as versatile tracking markers for identification and quantification of transplanted cancer cells in vivo. However, immune reactions against these markers can hamper the formation of syngraft tumors and metastasis that follows. Here, we report two transgenic (Tg) mouse lines that express nonfunctional mutant marker proteins, namely modified firefly luciferase (Luc2) or enhanced GFP (EGFP). These mice, named as Tg-mLuc2 and Tg-mEGFP, turned out to be immunologically tolerant to the respective tracking markers and thus efficiently accepted syngeneic cancer cells expressing the active forms of the markers. We then injected intrarectally the F 1 hybrid Tg mice (BALB/c × C57BL/6J) with Colon-26 (C26) colon cancer cells that originated from a BALB/c mouse. Even when C26 cells expressed active Luc2 or EGFP, they formed primary tumors in the Tg mice with only 10 4 cells per mouse compared with more than 10 6 cells required in the nontransgenic BALB/c hosts. Furthermore, we detected metastatic foci of C26 cells in the liver and lungs of the Tg mice by tracking the specific reporter activities. These results show the usefulness of the Tg mouse lines as recipients for transplantation experiments with the non-self tracking marker-expressing cells. © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

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.

Evaluation of a new five-injection, two-site,intradermal schedule for purified chick embryo cell rabies vaccine: A randomized, open-label, active-controlled trial in healthy adult volunteers in India

PubMed Central

Sudarshan, M.K.; Madhusudana, S.N.; Mahendra, B.J.; Ashwath Narayana, D.H.; Ananda Giri, M.S.; Popova, O.; Vakil, H.B.

2005-01-01

Background: Human rabies is an ongoing significant public health problem inmany developing countries, with India reporting the highest incidence of rabies-related deaths (∼20,000 per year). Many people living in India cannot afford the standard IM postexposure prophylaxis (PEP) with cell-culture vaccines, which are administered using a 5-dose regimen developed in Essen, Germany. A potentially less expensive intradermal (ID) regimen, based on the Essen regimen, has been developed at the Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India. Objective: The objective of this study was to compare the immunogenicity and local and systemic tolerability of the KIMS-1D regimen with those of the standard Essen IM regimen in healthy adult volunteers in India. Methods: This randomized, open-label, active-controlled trial was conductedat the Antirabies Clinic, Medical College, KIMS. Healthy adult volunteers were randomly assigned to receive purified chick embryo cell vaccine (PCECV) using the KIMS-1D regimen (0.1 mL injected ID at 2 body sites on days 0, 3, 7, 14, and 28 [“2-2-2-2-2”]) or the Essen IM regimen (1 mL injected IM at 1 body site on the same days Subjects were followed up for 365 days by the treating physician and encouraged to voluntarily report any adverse events (AEs). Serum rabies virus-neutralizing antibody (RVNA) concentrations were measured before the first injection on day 0 (baseline) and on days 14, 28, 90, 180, and 365, using the rapid fluorescent focus inhibition test. Results: Ninety-one subjects were enrolled and included in the tolerabilityand immunogenicity analyses. The ID group comprised 45 subjects (26 men, 19 women; mean [SD] age, 20.84 [1.48] years); the IM group, 46 subjects (28 men, 18 women; mean [SD] age, 21.02 [1.16] years). The most common local AEs were pain at the injection site (2/225 [0.9%] in the ID group and 10/230 [4.3%] in the IM group; P < 0.006) and itching at the injection site (5/225 [2.2%] in the ID group

Attenuation of primary nonfunction for syngeneic islet graft using sodium 4-phenylbutyrate.

PubMed

Fu, S-H; Chen, S-T; Hsu, B R-S

2005-05-01

Sodium 4-phenylbutyrate (4-SPB), an aromatic derivative of butyric acid, was examined to elucidate its effect on islet engraftment in a syngeneic transplantation model using C57BL/6 mice. Diabetic mice that received subrenal implantation of 150 islets on day 0 and oral administration of twice daily 4-SPB (500 mg/kg body weight) on days -2 through 28 displayed a significantly shorter duration of posttransplantation temporary hyperglycemia than diabetic mice that received islets in isotonic sodium chloride solution (NaCl), namely 16 +/- 2 (n = 12) vs 23 +/- 2 days (n = 7; P < .05). Four weeks after transplantation, the insulin content (IC) of grafts from mice treated with islets and 4-SPB was substantially higher than that of grafts from mice treated with islets and NaCl, namely 2.59 +/- 0.37 (n = 8) vs 1.36 +/- 0.36 mug (n = 13; P < .01). The IC of pancreatic remnants showed no significant difference between groups after 2 and 4 weeks of incubation. In vitro studies demonstrated that the net glucose-stimulated insulin secretion (GSIS) and the ratio of net GSIS to the IC of islets cultured with 4-SPB (1 mM) did not differ significantly from those cultured with NaCl. The lipopolysaccharide-stimulated secretions of IL-1beta, IL-10, and IFNgamma from peritoneal exudate monocytes were significantly reduced by co-incubation with 4-SPB (1 mM). In conclusion, our data suggest that daily administration of 4-SPB reduces primary nonfunction and enhances islet engraftment in a syngeneic mouse transplantation model.

Heparin allergy: delayed-type non-IgE-mediated allergic hypersensitivity to subcutaneous heparin injection.

PubMed

Trautmann, Axel; Seitz, Cornelia S

2009-08-01

Itching erythematous or eczematous plaques around injection sites are quite frequent side effects of heparin treatment and clinical symptoms of delayed-type non-IgE-mediated allergic hypersensitivity (DTH) to heparin. For diagnosis, intradermal, patch, and subcutaneous challenge tests with heparins are suitable. In most cases, changing the subcutaneous therapy from unfractionated to low molecular weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Hirudin polypeptides, which exhibit a different chemical structure, are a safe therapeutic alternative for subcutaneous application, however. Importantly, despite DTH to subcutaneously injected heparins, most patients tolerate heparin intravenously. Moreover, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration without prior testing may be justified.

An intradermal skin test for determination of immunity to varicella

PubMed Central

Somekh, E; Bujanover, Y; Tal, G; Dalal, I; Tanay, A; Lehman, D

2001-01-01

AIMS—To evaluate the usefulness of a diluted, inactivated solution of attenuated varicella vaccine in predicting susceptibility to varicella and its correlation with specific antibody titre to varicella.
METHODS—In a prospective blinded study, 63 healthy subjects (aged 2-43 years) were studied. Skin test solution was prepared from vials of OKA strain virus which was inactivated by exposure of the vials to room temperature for 10 days; solution was diluted at 1/50 with normal saline and kept at 4°C until used for skin testing. The material was injected intradermally. Serum samples were drawn prior to skin testing and kept at −70°C until analysis for antibody assay by the indirect fluorescent antibody (IFA) method.
RESULTS—Forty three patients were IFA antibody positive; 41 of them reacted to the skin test. One of the 20 IFA negative patients reacted to the skin test. Sixteen patients had two serological tests performed, one month apart. Four out of these 16 patients tested negative with the skin test. All four had negative serology on both samples. Six of the 12 IFA positive patients showed a boost in the antibody titre one month after application of the skin test. The specificity and sensitivity of the skin test compared to the IFA assay were both 95%, and the positive and negative predictive values were 97% and 90% respectively.
CONCLUSIONS—Results suggest that a varicella skin test prepared using this simple and relatively cheap method is a safe, sensitive, and specific tool by which to assess immunity to varicella.

 PMID:11719333

An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock

PubMed Central

Morefield, Garry L; Tammariello, Ralph F; Purcell, Bret K; Worsham, Patricia L; Chapman, Jennifer; Smith, Leonard A; Alarcon, Jason B; Mikszta, John A; Ulrich, Robert G

2008-01-01

Background Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy. Methods As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures. Results The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B. Conclusion Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component. The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product. PMID:18768085

Sensitization or tolerance to Mycobacterium leprae antigen by route of injection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shepard, C.C.; Walker, L.L.; Van Landingham, R.M.

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 atmore » 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.« less

Intradermal reactions to purified protein derivative in patients with diabetes mellitus.

PubMed

Nwabudike, L C; Ionescu-Tîrgovişte, C

2005-01-01

Diabetes mellitus is known to adversely affect the immune system. Immune dysfunction is also associated with the etiology of diabetes mellitus. Immune dysfunction is associated with diminished chemotactic, phagocytic and monocyte activity. There is also increased T-cell activity. All these are associated with acute hyperglycemia. We investigated the cellular arm of the immune system of patients with diabetes mellitus using intradermal reactions (IDR) to purified protein derivative (PPD). Both groups high blood glucose [HBG] vs. low blood glucose [LBG]) were homogeneous in terms of size and sex and average age (24. vs. 22.; 21 F vs 25 M; 56.5yrs. vs. 54.5 yrs.). The LBG had a greater average duration of diabetes (13.6 yrs vs. 9.3 yrs), which suggests an increased tendency to complications of diabetes mellitus. The results showed an average blood glucose and IDR (HBG vs. LBG) of 235.8 +/- 46.5 mg/dl vs. 144.3 +/- 26.7 mg/dl and 18.5 +/- 8.5 mm vs. 12.2 +/- 7.0 mm respectively. These results showed that IDR is significantly affected by hyperglycemia. This increased IDR may be a consequence of the synergy between interferon-gamma and tumor necrosis factor alpha which is a significant factor in diabetes. Also, there is an accentuation of this synergy following injection of PPD. It appears to be clear that IDR to PPD may be influenced by the diabetic state, especially acute hyperglycemia. However, it also appears that IDR to PPD may not be an adequate method for assessing cutaneous cell-mediated immunity.

A syngeneic glioma model to assess the impact of neural progenitor target cell age on tumor malignancy

PubMed Central

Mikheev, Andrei M; Stoll, Elizabeth A; Mikheeva, Svetlana A; Maxwell, John-Patrick; Jankowski, Pawel P; Ray, Sutapa; Uo, Takuma; Morrison, Richard S; Horner, Philip J; Rostomily, Robert C

2010-01-01

Summary Human glioma incidence, malignancy and treatment resistance are directly proportional to patient age. Cell intrinsic factors are reported to contribute to human age-dependent glioma malignancy but suitable animal models to examine the role of aging are lacking. Here we developed an orthotopic syngeneic glioma model to test the hypothesis that the age of neural progenitor cells (NPCs), presumed cells of glioma origin, influences glioma malignancy. Gliomas generated from transformed donor 3-, 12-, and 18-month-old NPCs in same-aged adult hosts all formed highly invasive glial tumors that phenocopied the human disease. Survival analysis indicated increased malignancy of gliomas generated from older 12- and 18-month-old transformed NPCs compared with their 3-month counterparts (median survival of 38.5 and 42.5 vs. 77 days, respectively). This study showed for the first time that age of target cells at the time of transformation can affect malignancy and demonstrated the feasibility of a syngeneic model using transformed NPCs for future examination of the relative impacts of age-related cell intrinsic and cell-extrinsic factors in glioma malignancy. PMID:19489742

Noncoherent-intense-pulsed light for the treatment of relapsing hairy intradermal melanocytic nevus after shave excision.

PubMed

Moreno-Arias, G A; Ferrando, J

2001-01-01

Few reports about melanocytic lesions treatment by means of noncoherent-intense-pulsed light (NCIPL) have been published. Here we evaluate the clinical results of a relapsing hairy intradermal melanocytic nevus treated with a noncoherent-intense-pulsed light source. A facial repigmented hairy intradermal melanocytic nevus that relapsed after shave excision, received four treatment sessions of a noncoherent-intense-pulsed light source (EpiLight, ESC Medical Systems Ltd, Israel) with the following parameters: 755 nm, a fluence energy of 40-42.5 J/cm(2), triple mode, a pulse width of 3.8 ms, and a delay of 20 ms, at 4-week intervals. Complete pigment clearance and hair removal was obtained. We have neither observed repigmentation nor hair regrowth after a 6 month-follow-up. No side effects were documented. Noncoherent-intense-pulse light is an effective treatment for hairy-pigmented melanocytic nevus. Copyright 2001 Wiley-Liss, Inc.

Long survival and immunologic reconstitution following transplantation with syngeneic or allogeneic fetal liver and neonatal spleen cells. [X radiation, mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yunis, E.J.; Fernandes, G.; Smith, J.

1976-12-01

Spleen cells from newborn syngeneic and allogeneic mice that lack fully differentiated T lymphocytes can be used as a hematopoietic source to reconstitute both hematopoietic and lymphoid systems of lethally irradiated mice without producing a GVHR. Fetal liver cells from syngeneic and allogeneic mice that lack postthymic T lymphocytes can also be used for hematopoietic and immunologic reconstitution of lethally irradiated mice without producing GVHR. Immunologic deficiency is observed in some experiments in mice given supralethal irradiation (1000 R) and fetal liver as reconstituting hematopoietic tissue. The findings suggest that T cells, at an early stage of differentiation, are moremore » susceptible to tolerance induction than are T lymphocytes at later stages of differentiation and do not, in general, produce GVHR. It is postulated that hematopoietic cells, free of postthymic lymphoid cells, can be used for hematopoietic or immunologic reconstitution and celular engineering without producing GVHD.« less

Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes

PubMed Central

Hurst, David

2017-01-01

Objective. To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods. A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results. Posthurricane patients had 34.6 times more positive results (p < 0.0001) at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes (p < 0.0001); average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes (p < 0.0001). The posthurricane population was younger (p < 0.001) and included more patients with asthma or lower respiratory symptoms (p < 0.05). Conclusion. Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas. PMID:28491100

Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes.

PubMed

Saporta, Diego; Hurst, David

2017-01-01

Objective . To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods . A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results . Posthurricane patients had 34.6 times more positive results ( p < 0.0001) at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes ( p < 0.0001); average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes ( p < 0.0001). The posthurricane population was younger ( p < 0.001) and included more patients with asthma or lower respiratory symptoms ( p < 0.05). Conclusion . Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas.

Cluster Intradermal DNA Vaccination Rapidly Induces E7-specific CD8+ T Cell Immune Responses Leading to Therapeutic Antitumor Effects

PubMed Central

Peng, Shiwen; Trimble, Cornelia; Alvarez, Ronald D.; Huh, Warner K.; Lin, Zhenhua; Monie, Archana; Hung, Chien-Fu; Wu, T.-C.

2010-01-01

Intradermal administration of DNA vaccines via a gene gun represents a feasible strategy to deliver DNA directly into the professional antigen-presenting cells (APCs) in the skin. This helps to facilitate the enhancement of DNA vaccine potency via strategies that modify the properties of APCs. We have previously demonstrated that DNA vaccines encoding human papillomavirus type 16 (HPV-16) E7 antigen linked to calreticulin (CRT) are capable of enhancing the E7-specific CD8+ T cell immune responses and antitumor effects against E7-expressing tumors. It has also been shown that cluster (short-interval) DNA vaccination regimen generates potent immune responses in a minimal timeframe. Thus, in the current study we hypothesize that the cluster intradermal CRT/E7 DNA vaccination will generate significant antigen-specific CD8+ T cell infiltrates in E7-expressing tumors in tumor-bearing mice, leading to an increase in apoptotic tumor cell death. We found that cluster intradermal CRT/E7 DNA vaccination is capable of rapidly generating a significant number of E7-specific CD8+ T cells, resulting in significant therapeutic antitumor effects in vaccinated mice. We also observed that cluster intradermal CRT/E7 DNA vaccination in the presence of tumor generates significantly higher E7-specific CD8+ T cell immune responses in the systemic circulation as well as in the tumors. In addition, this vaccination regimen also led to significantly lower levels of CD4+Foxp3+ T regulatory cells and myeloid suppressor cells compared to vaccination with CRT DNA in peripheral blood and in tumor infiltrating lymphocytes, resulting in an increase in apoptotic tumor cell death. Thus, our study has significant potential for future clinical translation. PMID:18401437

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. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

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.

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.

Immune responses after fractional doses of inactivated poliovirus vaccine using newly developed intradermal jet injectors: a randomized controlled trial in Cuba.

PubMed

Resik, Sonia; Tejeda, Alina; Mach, Ondrej; Fonseca, Magile; Diaz, Manuel; Alemany, Nilda; Garcia, Gloria; Hung, Lai Heng; Martinez, Yenisleydis; Sutter, Roland

2015-01-03

The World Health Organization recommends that, as part of the new polio endgame, a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5th of full dose) IPV (fIPV) intradermally may reduce costs, but its administration is cumbersome with BCG needle and syringe. We evaluated performance of two newly developed intradermal-only jet injectors and compared the immune response induced by fIPV with that induced by full-dose IPV. Children between 12 and 20 months of age, who had previously received two doses of OPV, were enrolled in Camaguey, Cuba. Subjects received a single dose of IPV (either full-dose IPV intramuscularly with needle and syringe or fIPV intradermally administered with one of two new injectors or with BCG needle or a conventional needle-free injector). Serum was tested for presence of poliovirus neutralizing antibodies on day 0 (pre-IPV) and on days 3, 7 and 21 (post-vaccination). Complete data were available from 74.2% (728/981) subjects. Baseline median antibody titers were 713, 284, and 113 for poliovirus types 1, 2, and 3, respectively. Seroprevalence at study end were similar across the intervention groups (≥ 94.8%). The immune response induced with one new injector was similar to BCG needle and to the conventional injector; and superior to the other new injector. fIPV induced significantly lower boosting response compared to full-dose IPV. No safety concerns were identified. One of the two new injectors demonstrated its ability to streamline intradermal fIPV administration, however, further investigations are needed to assess the potential contribution of fIPV in the polio endgame plan. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PRODUCTION OF IMMUNOLOGICAL TOLERANCE IN MICE AFTER REPEATED INJECTIONS OF DISRUPTED SPLEEN CELLS

PubMed Central

Martinez, C.; Smith, J. M.; Blaese, M.; Good, R. A.

1963-01-01

1. Tolerance of male skin isografts has been regularly produced in female mice of the C57B1 strain sublines 1, 4, and 6 during adult life by repeated injection of completely disrupted spleen cells derived from male donors. The tolerant state is long-lasting since such grafts have remained in place more than 9 months. 2. Prolonged survival of homotransplants of skin has regularly been produced in DBA/2 mice during adult life by repeated injections of completely disrupted spleen cells from Balb/C donors. When injections of disrupted spleen cell material are continued over a sufficiently long period, permanent acceptance of the skin homografts may be obtained between these strains. 3. Immunological tolerance across even the strong H-2 histocompatibility barrier was obtained in the neonatal period and during adult life by repeated injection of disrupted spleen cell preparations. The tolerant state has been revealed by both mammary adenocarcinoma and skin homografting across this strong histocompatibility barrier. 4. In contradistinction to the tolerant state produced by injection of intact spleen cells in neonatal animals or during adult life or that produced by parabiotic union, the tolerance produced by repeated injection of disrupted spleen cell preparations cannot be transferred to syngenic neonatal mice with spleen cells of the tolerant animal. 5. The implications of these findings in transplantation biology and in consideration of the basic nature of tolerance are discussed. PMID:14087619

Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol☆

PubMed Central

Wallace, Anne M.; Hoh, Carl K.; Limmer, Karl K.; Darrah, Denise D.; Schulteis, Gery; Vera, David R.

2014-01-01

Lymphoseek is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node (SLN) mapping. We conducted a clinical trial which measured the injection site clearance and sentinel lymph node accumulation after a single intradermal injection of Lymphoseek or unfiltered [99mTc]sulfur colloid (TcSC) using a “2-day” protocol for SLN mapping of breast cancer. Eleven patients with breast cancer participated in this study. Five patients received an intradermal administration of 1.0 nmol of 99mTc-labeled Lymphoseek; SLN mapping was performed on four subjects within 19 to 27 h. Six subjects received an intradermal administration of TcSC; SLN mapping was performed on five subjects within 18 to 26 h. Lymphoseek exhibited a significantly (P<.001) faster injection site clearance than TcSC. The mean Lymphoseek clearance half-time was 2.18±1.09 h compared to 57.4±92.8 h for TcSC. The mean sentinel lymph node uptake of Lymphoseek (1.5±1.7%) and TcSC (3.5±3.1%) was statistically equivalent (P=.213). When an intradermal injection is employed, Lymphoseek demonstrated faster injection site clearance than unfiltered [99mTc]sulfur colloid and persistent SLN accumulation for at least 24 h. PMID:19647175

Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice.

PubMed

Chinnasamy, Dhanalakshmi; Yu, Zhiya; Theoret, Marc R; Zhao, Yangbing; Shrimali, Rajeev K; Morgan, Richard A; Feldman, Steven A; Restifo, Nicholas P; Rosenberg, Steven A

2010-11-01

Immunotherapies based on adoptive cell transfer are highly effective in the treatment of metastatic melanoma, but the use of this approach in other cancer histologies has been hampered by the identification of appropriate target molecules. Immunologic approaches targeting tumor vasculature provide a means for the therapy of multiple solid tumor types. We developed a method to target tumor vasculature, using genetically redirected syngeneic or autologous T cells. Mouse and human T cells were engineered to express a chimeric antigen receptor (CAR) targeted against VEGFR-2, which is overexpressed in tumor vasculature and is responsible for VEGF-mediated tumor progression and metastasis. Mouse and human T cells expressing the relevant VEGFR-2 CARs mediated specific immune responses against VEGFR-2 protein as well as VEGFR-2-expressing cells in vitro. A single dose of VEGFR-2 CAR-engineered mouse T cells plus exogenous IL-2 significantly inhibited the growth of 5 different types of established, vascularized syngeneic tumors in 2 different strains of mice and prolonged the survival of mice. T cells transduced with VEGFR-2 CAR showed durable and increased tumor infiltration, correlating with their antitumor effect. This approach provides a potential method for the gene therapy of a variety of human cancers.

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

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.

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. Copyright © 2013 Elsevier Inc. All rights reserved.

[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.

A pilot study of the validation of percutaneous testing in cats.

PubMed

Rossi, Michael A; Messinger, Linda; Olivry, Thierry; Hoontrakoon, Raweewan

2013-10-01

Intradermal testing is useful for the identification of environmental allergens to which cats could be hypersensitive; intradermal test reactions are often subtle and difficult to interpret in cats. Percutaneous testing is the standard technique for the detection of significant environmental allergens in people, but it has not yet been evaluated in cats with hypersensitivity dermatitis. The purpose of this study was to evaluate and compare the skin test responses of healthy cats to percutaneous application and intradermal injections of control solutions. Ten clinically healthy cats were studied. Percutaneous applications of 0.0275 and 0.1 mg/mL aqueous histamine, 6 mg/mL glycerinated histamine, 0.9% buffered saline and 50% glycerosaline solution were performed using Greer Pick (Greer Laboratories, Lenoir, NC, USA) and Duotip-Test II (Lincoln Diagnostics, Decatur, IL, USA) percutaneous applicators. Reactions were compared with intradermal injections of 0.0275 mg/mL aqueous histamine and 0.9% buffered saline as controls. Positive responses to histamine solutions were significantly greater with the Greer Pick than with the Duotip-Test II. There were no significant differences between the histamine reactions using the Greer Pick applicator and the intradermal injections. Percutaneous reactions to histamine were more well demarcated and easier to read than intradermal injection reactions. Reactions to the saline controls were not noted. Percutaneous application of 6 mg/mL glycerinated histamine solution, 50% glycerosaline solution and 0.9% buffered saline produced similar positive and negative control wheals. These observations warrant further studies of percutaneous allergen testing in cats with hypersensitivity dermatitis. © 2013 ESVD and ACVD.

Cyclin-dependent kinase 4 signaling acts as a molecular switch between syngenic differentiation and neural transdifferentiation in human mesenchymal stem cells

PubMed Central

Lee, Janet; Baek, Jeong-Hwa; Choi, Kyu-Sil; Kim, Hyun-Soo; Park, Hye-Young; Ha, Geun-Hyoung; Park, Ho; Lee, Kyo-Won; Lee, Chang Geun; Yang, Dong-Yun; Moon, Hyo Eun; Paek, Sun Ha; Lee, Chang-Woo

2013-01-01

Multipotent mesenchymal stem/stromal cells (MSCs) are capable of differentiating into a variety of cell types from different germ layers. However, the molecular and biochemical mechanisms underlying the transdifferentiation of MSCs into specific cell types still need to be elucidated. In this study, we unexpectedly found that treatment of human adipose- and bone marrow-derived MSCs with cyclin-dependent kinase (CDK) inhibitor, in particular CDK4 inhibitor, selectively led to transdifferentiation into neural cells with a high frequency. Specifically, targeted inhibition of CDK4 expression using recombinant adenovial shRNA induced the neural transdifferentiation of human MSCs. However, the inhibition of CDK4 activity attenuated the syngenic differentiation of human adipose-derived MSCs. Importantly, the forced regulation of CDK4 activity showed reciprocal reversibility between neural differentiation and dedifferentiation of human MSCs. Together, these results provide novel molecular evidence underlying the neural transdifferentiation of human MSCs; in addition, CDK4 signaling appears to act as a molecular switch from syngenic differentiation to neural transdifferentiation of human MSCs. PMID:23324348

Impact of Sodium Bicarbonate-Buffered Lidocaine on Patient Pain During Image-Guided Breast Biopsy.

PubMed

Vasan, Alison; Baker, Jay A; Shelby, Rebecca A; Soo, Mary Scott C

2017-09-01

This randomized, double-blind controlled study evaluated the effectiveness of sodium bicarbonate-buffered lidocaine on reducing pain during imaging-guided breast biopsies. This prospective, HIPAA-compliant study randomly assigned 85 women undergoing ultrasound- or stereotactic-guided core-needle breast biopsies to receive intradermally and intraparenchymally either 1% lidocaine buffered with sodium bicarbonate (9:1 ratio) (bicarbonate study group) or 1% lidocaine alone (control group). Pain was evaluated using a 0-to-10 Likert pain scale during both intradermal and intraparenchymal anesthesia injections and during tissue sampling. Prebiopsy breast pain, anxiety, medical history, demographics, biopsy type, radiologist level of training, breast density, and lesion histology were recorded. Data were analyzed using analysis of variance and analysis of covariance. Unadjusted mean pain scores were 1.47 and 2.07 (study and control groups, respectively; P = .15) during intradermal injections, and 1.84 and 2.98 (study and control groups, respectively; P = .03) during intraparenchymal injections. Tissue sampling mean pain scores were .81 and 1.71 (study and control groups, respectively; P = .07). Moderator analyses found (1) among patients with preprocedural pain, those in the bicarbonate group experienced less intradermal injection pain (0.85 ± 1.23) than patients in the control group (2.50 ± 2.09); (2) among patients with fatty or scattered fibroglandular tissue, those in the bicarbonate group (1.35 ± 1.95) experienced less intraparenchymal injection pain than the control group (3.52 ± 3.13); and (3) during ultrasound-guided biopsies, patients in the bicarbonate group experienced less tissue-sampling pain (0.23 ± 0.63) than the control group (1.79 ± 3.05). Overall, buffering lidocaine with sodium bicarbonate significantly reduced pain during intraparenchymal injections, and additional pain reduction was found in certain patient subgroups during intradermal

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

PubMed Central

Goddard, Erica T.; Fischer, Jacob; Schedin, Pepper

2016-01-01

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas. PMID:28060292

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer.

PubMed

Goddard, Erica T; Fischer, Jacob; Schedin, Pepper

2016-12-26

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas.

Accuracy and Significance of Polymerase Chain Reaction Detection of Sentinel Node Metastases in Breast Cancer Patients

DTIC Science & Technology

2000-10-01

oral presentation at the 1 998 AACR meeting and on the subsequent Cancer Research article, many investigators in the field have abandoned K19 as a...1999) "Comparison of Intradermal and Subcutaneous Injections in Lymphatic Mapping." Oral presentation_at the 33rd Annual Meeting of the Association of...Lannin D, Tafra L. Comparison of Intradermal and Subcutaneous Injections in Lymphatic Mapping, Oral presentation at the 33rd Annual Meeting of the

Intradermal immunization with inactivated swine influenza virus and adjuvant polydi(sodium carboxylatoethylphenoxy)phosphazene (PCEP) induced humoral and cell-mediated immunity and reduced lung viral titres in pigs.

PubMed

Magiri, Royford; Lai, Ken; Chaffey, Alyssa; Zhou, Yan; Pyo, Hyun-Mi; Gerdts, Volker; Wilson, Heather L; Mutwiri, George

2018-03-14

Swine influenza virus is endemic worldwide and it is responsible for significant economic losses to the swine industry. A vaccine that stimulates a rapid and long-lasting protective immune response to prevent this infection is highly sought. Poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP) has demonstrated adjuvant activity when formulated as part of multiple vaccines in mice and pigs. In this study we examined the magnitude and type of immune response induced in pigs vaccinated via the intramuscular or intradermal routes with inactivated swine influenza virus (SIV) H1N1 vaccine formulated with PCEP. Intradermal administration of PCEP-adjuvanted inactivated SIV vaccine stimulated significant anti-SIV antibody titres, increased neutralizing antibodies, and significantly reduced lung virus load with limited reduction of gross lung lesions after challenge with virulent H1N1 relative to control animals. These results indicate that PCEP may be effective as a vaccine adjuvant against swine influenza viruses in pigs and should be considered a potential candidate adjuvant for future swine intradermal influenza vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

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

Excitation of mouse superficial dorsal horn neurons by histamine and/or PAR-2 agonist: potential role in itch.

PubMed

Akiyama, Tasuku; Carstens, Mirela Iodi; Carstens, E

2009-10-01

Recent studies have suggested the existence of separate transduction mechanisms and sensory pathways for histamine and nonhistaminergic types of itch. We studied whether histamine and an agonist of the protease-activated receptor (PAR)-2, associated with nonhistaminergic itch, excite murine dorsal horn neurons. Single units were recorded in superficial lumbar dorsal horn of adult ICR mice anesthetized with pentobarbital. Unit activity was searched using a small intradermal hindpaw injection of histamine or the PAR-2 agonist SLIGRL-NH2. Isolated units were subsequently challenged with intradermal histamine followed by SLIGRL-NH2 (each 50 microg/1 microl) or reverse order, followed by mechanical, thermal, and algogenic stimuli. Forty-three units were classified as wide dynamic range (62%), nociceptive specific (22%), or mechano insensitive (16%). Twenty units gave prolonged (mean, 10 min) discharges to intradermal injection of histamine; 76% responded to subsequent SLIGRL-NH2, often more briefly. Units additionally responded to noxious heat (63%), cooling (43%), topical mustard oil (53%), and intradermal capsaicin (67%). Twenty-two other units gave prolonged (mean, 5 min) responses to initial intradermal injection of SLIGRL-NH2; 85% responded to subsequent intradermal histamine. They also responded to noxious heat (75%), mustard oil (93%), capsaicin (63%), and one to cooling. Most superficial dorsal horn neurons were excited by both histamine and the PAR-2 agonist, suggesting overlapping pathways for histamine- and non-histamine-mediated itch. Because the large majority of pruritogen-responsive neurons also responded to noxious stimuli, itch may be signaled at least partly by a population code.

Duration of efficacy increases with the repetition of botulinum toxin A injections in primary palmar hyperhidrosis: a study of 28 patients.

PubMed

Lecouflet, Marie; Leux, Christophe; Fenot, Marion; Célerier, Philippe; Maillard, Hervé

2014-06-01

Intradermal injections of botulinum toxin are effective but transitory in primary palmar hyperhidrosis. These injections are repeated when the symptoms recur. We do not know how the duration of efficacy changes when injections are repeated. In this retrospective study, we aimed to investigate the change in the duration of efficacy of botulinum toxin A (Dysport, Ipsen, Boulogne-Billancourt, France) with the repetition of injections in patients with primary palmar hyperhidrosis. From May 2001 to April 2012, 28 patients were treated with a dose of 250 U of botulinum toxin A per palm. We compared the duration of efficacy of the first and last toxin injections. The median duration of efficacy was 7 months for the first injection and 9.5 months for the last, the difference being statistically significant (P = .0002). Study limitations include a relatively small number of patients treated at a single center and evaluated retrospectively. To our knowledge, this study is the first to report a significant increase in the duration of efficacy of botulinum toxin A injections with the repetition of injections in patients with primary palmar hyperhidrosis. The reasons for this effect may be linked to the mechanism of action of botulinum toxin, and may improve our understanding of its pharmacologic effects. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Syngeneic Transplantation of Olfactory Ectomesenchymal Stem Cells Restores Learning and Memory Abilities in a Rat Model of Global Cerebral Ischemia.

PubMed

Veron, Antoine D; Bienboire-Frosini, Cécile; Girard, Stéphane D; Sadelli, Kevin; Stamegna, Jean-Claude; Khrestchatisky, Michel; Alexis, Jennifer; Pageat, Patrick; Asproni, Pietro; Mengoli, Manuel; Roman, François S

2018-01-01

Stem cells are considered as promising tools to repair diverse tissue injuries. Among the different stem cell types, the "olfactory ectomesenchymal stem cells" (OE-MSCs) located in the adult olfactory mucosa stand as one of the best candidates. Here, we evaluated if OE-MSC grafts could decrease memory impairments due to ischemic injury. OE-MSCs were collected from syngeneic F344 rats. After a two-step global cerebral ischemia, inducing hippocampal lesions, learning abilities were evaluated using an olfactory associative discrimination task. Cells were grafted into the hippocampus 5 weeks after injury and animal's learning abilities reassessed. Rats were then sacrificed and the brains collected for immunohistochemical analyses. We observed significant impairments in learning and memory abilities following ischemia. However, 4 weeks after OE-MSC grafts, animals displayed learning and memory performances similar to those of controls, while sham rats did not improve them. Immunohistochemical analyses revealed that grafts promoted neuroblast and glial cell proliferation, which could permit to restore cognitive functions. These results demonstrated, for the first time, that syngeneic transplantations of OE-MSCs in rats can restore cognitive abilities impaired after brain injuries and provide support for the development of clinical studies based on grafts of OE-MSCs in amnesic patients following brain injuries.

The use of serological tests in combination with the intradermal tuberculin test maximizes the detection of tuberculosis infected goats.

PubMed

Bezos, Javier; Roy, Álvaro; Infantes-Lorenzo, José Antonio; González, Isabel; Venteo, Ángel; Romero, Beatriz; Grau, Anna; Mínguez, Olga; Domínguez, Lucas; de Juan, Lucía

2018-05-01

The diagnosis of tuberculosis (TB) in goats is based mainly on the single and comparative intradermal tuberculin (SIT and CIT) tests and, exceptionally, on the interferon-gamma (IFN-γ) assay, however they are not perfect in terms of sensitivity and specificity. Nevertheless, various serological assays that provide a potential cost-effective approach for the control of TB are also available or under development, and a variety of results have been reported regarding the ability of these tests to detect infected animals, particularly in the early stages of infection. In the present study, SIT/CIT and IFN-γ tests and three different serological assays were evaluated during two consecutive herd testing events in a recently infected caprine herd (n = 447) with a high prevalence of infection in order to evaluate their performance and provide field data with which to improve the TB control programs in this species. The proportion of infected animals that tested positive among all the infected goats (T+/I+ value) in the last herd testing event ranged from 26.2% (IC95%; 19.3-34.5) to 85.7% (IC95%; 78.5-90.7) using cell-based diagnostic tests. The SIT/SCIT tests detected more infected goats than the IFN-γ test, regardless of the interpretation criteria. The T+/I+ value of serology was 83.2 (IC95%; 75.2-89), although it increased significantly (P < 0.05) when using samples collected 15 days after the intradermal test (100%, IC95%; 97-100). In general, a parallel interpretation of intradermal tests with serology maximized the detection of infected goats. These results demonstrate that serological tests are valuable diagnostic tools to maximize the detection of TB infected goats, even in recent outbreaks, accelerating the eradication process. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

The effect of subareolar isosulfan blue injection on pulse oximeter readings.

PubMed

Zengel, Baha; Yararbas, Ulkem; Bingolballi, Ozge; Denecli, Ali Galip

2014-02-01

Besides several side effects including anaphylaxis, blue dyes are also known to cause false pulse oximeter readings. We aimed to examine the effects of subareolar isosulfan blue injection on pulse oximeter (SpO2) readings. The study group included 27 patients undergoing SLNB using both radiocolloid and isosulfan blue. Another group of 27 patients constituted the control group. Pulse oximeter readings were compared. SpO2 decline ≥4 % was defined as significant. All but one (96.2 %) of the patients in the study group showed SpO2 declines, compared to only one patient in the control group. Median ± Interqartile Range (IR) SpO2 decrease was 3.0 ± 4.0 % in the study and 0.0 ± 1.0 % in the control group (p < 0.001). There were significant (≥4 %) SpO2 decreases in 13 (48.1 %) patients in the study group. Statistically significant differences were noted between the two groups in all recordings between 15 and 180 min (p < 0.001). Initial time for SpO2 fall and the time to the lowest SpO2 recording were 10.0 ± 10.0 and 40.0 ± 30.0 min respectively. Using subareolar injection, the frequency of false readings is comparable with intraparenchymal injections, and is higher than intradermal injections. Time to peak SpO2 fall, and the recovery period, are delayed in the subareolar technique.

Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells.

PubMed

Kochenderfer, James N; Yu, Zhiya; Frasheri, Dorina; Restifo, Nicholas P; Rosenberg, Steven A

2010-11-11

Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. To evaluate anti-CD19-CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. One infusion of anti-CD19-CAR-transduced T cells completely eliminated normal B cells from mice for at least 143 days. Anti-CD19-CAR-transduced T cells eradicated intraperitoneally injected lymphoma cells and large subcutaneous lymphoma masses. The antilymphoma efficacy of anti-CD19-CAR-transduced T cells was critically dependent on irradiation of mice before anti-CD19-CAR-transduced T-cell infusion. Anti-CD19-CAR-transduced T cells had superior antilymphoma efficacy compared with the anti-CD19 monoclonal antibody from which the anti-CD19 CAR was derived. Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19-CAR-transduced T cells in a clinically relevant murine model.

Semiconductor diode laser device adjuvanting intradermal vaccine

PubMed Central

Kimizuka, Yoshifumi; Callahan, John J.; Huang, Zilong; Morse, Kaitlyn; Katagiri, Wataru; Shigeta, Ayako; Bronson, Roderick; Takeuchi, Shu; Shimaoka, Yusuke; Chan, Megan P. K.; Zeng, Yang; Li, Binghao; Chen, Huabiao; Tan, Rhea Y. Y.; Dwyer, Conor; Mulley, Tyler; Leblanc, Pierre; Goudie, Calum; Gelfand, Jeffrey; Tsukada, Kosuke; Brauns, Timothy; Poznansky, Mark C.; Bean, David; Kashiwagi, Satoshi

2017-01-01

A brief exposure of skin to a low-power, non-tissue damaging laser light has been demonstrated to augment immune responses to intradermal vaccination. Both preclinical and clinical studies show that this approach is simple, effective, safe and well tolerated compared to standard chemical or biological adjuvants. Until now, these laser exposures have been performed using a diode-pumped solid-state laser (DPSSL) devices, which are expensive and require labor-intensive maintenance and special training. Development of an inexpensive, easy-to-use and small device would form an important step in translating this technology toward clinical application Here we report that we have established a handheld, near-infrared (NIR) laser device using semiconductor diodes emitting either 1061, 1258, or 1301 nm light that costs less than $4,000, and that this device replicates the adjuvant effect of a DPSSL system in a mouse model of influenza vaccination. Our results also indicate that a broader range of NIR laser wavelengths possess the ability to enhance vaccine immune responses, allowing engineering options for the device design. This small, low-cost device establishes the feasibility of using a laser adjuvant approach for mass-vaccination programs in a clinical setting, opens the door for broader testing of this technology with a variety of vaccines and forms the foundation for development of devices ready for use in the clinic. PMID:28365253

Semiconductor diode laser device adjuvanting intradermal vaccine.

PubMed

Kimizuka, Yoshifumi; Callahan, John J; Huang, Zilong; Morse, Kaitlyn; Katagiri, Wataru; Shigeta, Ayako; Bronson, Roderick; Takeuchi, Shu; Shimaoka, Yusuke; Chan, Megan P K; Zeng, Yang; Li, Binghao; Chen, Huabiao; Tan, Rhea Y Y; Dwyer, Conor; Mulley, Tyler; Leblanc, Pierre; Goudie, Calum; Gelfand, Jeffrey; Tsukada, Kosuke; Brauns, Timothy; Poznansky, Mark C; Bean, David; Kashiwagi, Satoshi

2017-04-25

A brief exposure of skin to a low-power, non-tissue damaging laser light has been demonstrated to augment immune responses to intradermal vaccination. Both preclinical and clinical studies show that this approach is simple, effective, safe and well tolerated compared to standard chemical or biological adjuvants. Until now, these laser exposures have been performed using a diode-pumped solid-state laser (DPSSL) devices, which are expensive and require labor-intensive maintenance and special training. Development of an inexpensive, easy-to-use and small device would form an important step in translating this technology toward clinical application. Here we report that we have established a handheld, near-infrared (NIR) laser device using semiconductor diodes emitting either 1061, 1258, or 1301nm light that costs less than $4000, and that this device replicates the adjuvant effect of a DPSSL system in a mouse model of influenza vaccination. Our results also indicate that a broader range of NIR laser wavelengths possess the ability to enhance vaccine immune responses, allowing engineering options for the device design. This small, low-cost device establishes the feasibility of using a laser adjuvant approach for mass-vaccination programs in a clinical setting, opens the door for broader testing of this technology with a variety of vaccines and forms the foundation for development of devices ready for use in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Residual Limb Hyperhidrosis Managed by Botulinum Toxin Injections, Enhanced by the Iodine-Starch Test: A Case Report.

PubMed

Hansen, Colby R; Godfrey, Bradeigh

2017-04-01

Hyperhidrosis of the residual limb is a common condition affecting patients with amputations. The iodine-starch test is used by dermatologists to identify focal areas of hyperhidrosis before treatment with botulinum toxin. Here, we describe a case of a patient with a transtibial amputation with moderate-to-severe hyperhidrosis who received intradermal botulinum toxin injections to treat residual limb hyperhidrosis, with particular emphasis given to the utility of the iodine-starch test in managing this common condition. The iodine-starch test successfully identified hyperhidrotic areas before treatment as well as confirmed the physiologic anhidrotic effect of the botulinum toxin treatment. V. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Lack of Humoral Immune Response to the Tetracycline (Tet) Activator in Rats Injected Intracranially with Tet-off rAAV Vectors

PubMed Central

Han, Ye; Chang, Qin A.; Virag, Tamas; West, Neva C.; George, David; Castro, Maria G.; Bohn, Martha C.

2010-01-01

The ability to safely control transgene expression from viral vectors is a long-term goal in the gene therapy field. We have previously reported tight regulation of GFP expression in rat brain using a self-regulating tet-off rAAV vector. The immune responses against tet regulatory elements observed by other groups in nonhuman primates after intramuscular injection of tet-on encoding vectors raise concerns about the clinical value of tet-regulated vectors. However, previous studies have not examined immune responses following injection of AAV vectors into brain. Therefore, rat striatum was injected with tet-off rAAV harboring a therapeutic gene for Parkinson's disease, either hAADC or hGDNF. The expression of each gene was tightly controlled by the tet-off regulatory system. Using an ELISA developed with purified GST-tTA protein, no detectable immunogenicity against tTA was observed in sera of rats that received an intrastriatal injection of either vector. In contrast, sera from rats intradermally injected with an adenovirus containing either tTA or rtTA, as positive controls, had readily detectable antibodies. These observations suggest that tet-off rAAV vectors do not elicit an immune response when injected into rat brain and that these may offer safer vectors for Parkinson's disease than vectors with constitutive expression. PMID:20164859

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

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

A clinical decision support system for diagnosis of Allergic Rhinitis based on intradermal skin tests.

PubMed

Jabez Christopher, J; Khanna Nehemiah, H; Kannan, A

2015-10-01

Allergic Rhinitis is a universal common disease, especially in populated cities and urban areas. Diagnosis and treatment of Allergic Rhinitis will improve the quality of life of allergic patients. Though skin tests remain the gold standard test for diagnosis of allergic disorders, clinical experts are required for accurate interpretation of test outcomes. This work presents a clinical decision support system (CDSS) to assist junior clinicians in the diagnosis of Allergic Rhinitis. Intradermal Skin tests were performed on patients who had plausible allergic symptoms. Based on patient׳s history, 40 clinically relevant allergens were tested. 872 patients who had allergic symptoms were considered for this study. The rule based classification approach and the clinical test results were used to develop and validate the CDSS. Clinical relevance of the CDSS was compared with the Score for Allergic Rhinitis (SFAR). Tests were conducted for junior clinicians to assess their diagnostic capability in the absence of an expert. The class based Association rule generation approach provides a concise set of rules that is further validated by clinical experts. The interpretations of the experts are considered as the gold standard. The CDSS diagnoses the presence or absence of rhinitis with an accuracy of 88.31%. The allergy specialist and the junior clinicians prefer the rule based approach for its comprehendible knowledge model. The Clinical Decision Support Systems with rule based classification approach assists junior doctors and clinicians in the diagnosis of Allergic Rhinitis to make reliable decisions based on the reports of intradermal skin tests. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pigmented Epithelioid Melanocytoma (PEM)/Animal Type Melanoma (ATM): Quest for an Origin. Report of One Unusual Case Indicating Follicular Origin and Another Arising in an Intradermal Nevus.

PubMed

Tarasen, Ashley; Carlson, J Andrew; Leonard, M Kathryn; Merlino, Glenn; Kaetzel, David; Slominski, Andrzej T

2017-08-15

Pigmented epithelioid melanocytoma (PEM) is a tumor encompassing epithelioid blue nevus of Carney complex (EBN of CNC) and was previously termed animal-type melanoma. Histologically PEMs are heavily pigmented spindled and epithelioid dermal melanocytic tumors with infiltrative borders, however, their origin remains unclear. Stem cells for the epidermis and hair follicle are located in the bulge area of the hair follicle with the potential to differentiate into multiple lineages. Multiple cutaneous carcinomas, including follicular cutaneous squamous cell carcinoma (FSCC), are thought to arise from stem cells in the follicular bulge. We present two cases of PEM/ATM in a 63 year-old male on the scalp with follicular origin and a 72 year-old female on the upper back arising in an intradermal nevus. Biopsy of both cases revealed a proliferation of heavily pigmented dermal nests of melanocytes with atypia. The Case 1 tumor was in continuation with the outer root sheath of the hair follicle in the bulge region. Case 2 arose in an intradermal melanocytic nevus. Rare mitotic figures, including atypical mitotic figures, were identified in both cases. We present two cases of PEM, with histologic evidence suggesting two origins: one from the follicular bulb and one from an intradermal nevus.

THE INFLUENCE OF INTRADERMAL INFECTION WITH STAPHYLOCOCCUS AND TYPHOID MICROBES ON THE COURSE OF ACUTE RADIATION SICKNESS IN GUINEA PIGS (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shal'nova, G.A.

1961-07-01

The course of staphylococcus and typhoid infection was studied in 252 intradermally infected guinea pigs irradiated with 100, 200, 300, and 500 r. Depression of leukocytic and phagocytic reactions in the inflammation sites and an increased number of microbes were observed on the 4th day following exposure. (R.V.J.)

Infusion pressure and pain during microneedle injection into skin of human subjects.

PubMed

Gupta, Jyoti; Park, Sohyun S; Bondy, Brian; Felner, Eric I; Prausnitz, Mark R

2011-10-01

Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures caused more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Subcutaneous adipose tissue thickness in adults - correlation with BMI and recommendations for pen needle lengths for subcutaneous self-injection.

PubMed

Ludescher, Burkhard; Rommel, Marc; Willmer, Tobias; Fritsche, Andreas; Schick, Fritz; Machann, Juergen

2011-12-01

One of the aims of a subcutaneous (SC) injection is to avoid intradermal or intramuscular injections. Pen systems are an alternative solution to single-use syringes and have become standard for example diabetes therapy. Shorter and smaller needles minimize pain and the risk of intramuscular injections. The thickness of subcutaneous adipose tissue (SCAT) varies with position and with body mass index (BMI). The aim of this study was the creation of a map of SCAT thickness at typical spots for SC self-injection. MRI scans of 116 prospectively enroled volunteers (56 men and 60 women) were analysed. SCAT thickness was determined at 17 spots over the abdominal wall, left thigh, buttocks and upper arm, typical sites for subcutaneous self-injection. SCAT thicknesses were correlated with BMI and waist-to-hip ratio (WHR), and a linear curve fit was performed. The best fitting linear functions for the prediction of the SCAT thickness dependent on BMI and WHR were derived. Correlations between SCAT and BMI were higher (0·67-0·21) than with WHR (-0·67 to 0·09). In women, correlation coefficients between SCAT data at the abdomen and BMI/WHR were higher than in men. On the other hand, data showed better correlations at the extremities in men. The data, with correlation between BMI and fat thickness at different injection sites in relation to gender, provide guidance in selecting an adequate pen needle length for deep and safe subcutaneous self-injection. WHR was a much weaker predictor when compared to BMI. © 2011 Blackwell Publishing Ltd.

Pigmented Epithelioid Melanocytoma (PEM)/Animal Type Melanoma (ATM): Quest for an Origin. Report of One Unusual Case Indicating Follicular Origin and Another Arising in an Intradermal Nevus †

PubMed Central

Tarasen, Ashley; Carlson, J. Andrew; Leonard, M. Kathryn; Merlino, Glenn; Kaetzel, David

2017-01-01

Pigmented epithelioid melanocytoma (PEM) is a tumor encompassing epithelioid blue nevus of Carney complex (EBN of CNC) and was previously termed animal-type melanoma. Histologically PEMs are heavily pigmented spindled and epithelioid dermal melanocytic tumors with infiltrative borders, however, their origin remains unclear. Stem cells for the epidermis and hair follicle are located in the bulge area of the hair follicle with the potential to differentiate into multiple lineages. Multiple cutaneous carcinomas, including follicular cutaneous squamous cell carcinoma (FSCC), are thought to arise from stem cells in the follicular bulge. We present two cases of PEM/ATM in a 63 year-old male on the scalp with follicular origin and a 72 year-old female on the upper back arising in an intradermal nevus. Biopsy of both cases revealed a proliferation of heavily pigmented dermal nests of melanocytes with atypia. The Case 1 tumor was in continuation with the outer root sheath of the hair follicle in the bulge region. Case 2 arose in an intradermal melanocytic nevus. Rare mitotic figures, including atypical mitotic figures, were identified in both cases. We present two cases of PEM, with histologic evidence suggesting two origins: one from the follicular bulb and one from an intradermal nevus. PMID:28809777

Immunobiologic effects of cytokine gene transfer of the B16-BL6 melanoma.

PubMed

Strome, S E; Krauss, J C; Cameron, M J; Forslund, K; Shu, S; Chang, A E

1993-12-01

The genetic modification of tumors offers an approach to modulate the host immune response to relatively weak native tumor antigens. We examined the immunobiologic effects of various cytokine genes transferred into the poorly immunogenic B16-BL6 murine melanoma. Retroviral expression vectors containing cDNAs for interleukin 2, interleukin 4, interferon gamma, or a neomycin-resistant control were electroporated into a B16-BL6 tumor clone. Selected transfected clones were examined for in vitro cytokine secretion and in vivo tumorigenicity. When cells from individual clones were injected intradermally into syngeneic mice, the interleukin 4-secreting clone grew significantly slower than did the neomycin-resistant transfected control, while the growth of the interleukin 2- and interferon gamma-expressing clones was not affected. Despite minimal cytokine secretion by interferon gamma-transfected cells, these cells expressed upregulated major histocompatibility class I antigen and were more susceptible to lysis by allosensitized cytotoxic T lymphocytes compared with parental or neomycin-resistant transfected tumor targets. We observed diverse immunobiologic effects associated with cytokine gene transfer into the B16-BL6 melanoma. Interleukin 4 transfection of tumor resulted in decreased in vivo tumorigenicity that may be related to a host immune response. Further studies to evaluate the host T-cell response to these gene-modified tumors are being investigated.

Comparison of intradermal and percutaneous testing to histamine, saline and nine allergens in healthy adult cats.

PubMed

Gentry, Christina M; Messinger, Linda

2016-10-01

Intradermal testing (IDT) in cats has potential limitations; this has led to an interest in novel testing methods. A pilot study demonstrated that healthy cats produced reliable percutaneous glycerinated (PG) histamine wheals, whereas percutaneously applied glycerosaline did not lead to wheal formation. The purpose of this study was to determine if percutaneously applied aqueous and glycerinated allergens would lead to irritant reactions in healthy cats. Percutaneous testing (PCT) with both glycerinated and aqueous allergens and IDT were compared in twelve healthy cats. The lateral thorax was clipped and histamine, saline and nine allergens were tested in rows. Objective and subjective evaluations were performed at 15, 20 and 25 min, and 4 h. Results were evaluated as positive or negative at 15, 20, 25 min and 4 h. Skin test reactions for intradermal (ID) histamine wheals were larger when compared to PG and percutaneous aqueous (PA) at the immediate reading points (P < 0.05) subjectively and objectively; however, PG was not significantly different from ID when compared as either positive (2-4) or negative (0-1). PG histamine and allergen reactions, when present, were larger than equivalent PA reactions. PG and PA allergens did not cause irritant reactions at tested concentrations. Bassia scoparia (kochia), when tested at 1000 PNU/mL with IDT, was suspected to be an irritant. Percutaneously (PCT) applied allergens did not cause irritant reactions in healthy cats. PG histamine wheals, although smaller than ID histamine wheals, were easily recognizable and PCT was simple to perform. © 2016 ESVD and ACVD.

Protective Immunity in Mice Achieved with Dry Powder Formulation and Alternative Delivery of Plague F1-V Vaccine▿

PubMed Central

Huang, Joanne; D'Souza, Ajit J.; Alarcon, Jason B.; Mikszta, John A.; Ford, Brandi M.; Ferriter, Matthew S.; Evans, Michelle; Stewart, Todd; Amemiya, Kei; Ulrich, Robert G.; Sullivan, Vincent J.

2009-01-01

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V fusion protein of Y. pestis for vaccination against plaque in a mouse model. Mice were immunized with reconstituted spray-freeze-dried F1-V powder via intramuscular injection, microneedle-based intradermal delivery, or noninvasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against lethal subcutaneous challenge with 1,000 50% lethal doses of Y. pestis at levels equivalent to those elicited by unprocessed liquid formulations (70 to 90% protection). The feasibility of intradermal and intranasal delivery of reconstituted powder F1-V vaccine was also demonstrated. Overall, microneedle-based intradermal delivery was shown to be similar in efficacy to intramuscular injection, while intranasal administration required an extra dose of vaccine to achieve similar protection. In addition, the results suggest that seroconversion against F1 may be a better predictor of protection against Y. pestis challenge than seroconversion against either F1-V or V. In summary, we demonstrate the preclinical feasibility of using a reconstituted powder F1-V formulation and microneedle-based intradermal delivery to provide protective immunity against plague in a mouse model. Intranasal delivery, while feasible, was less effective than injection in this study. The potential use of these alternative delivery methods and a powder vaccine formulation may result in substantial health and economic benefits. PMID:19261773

Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.

PubMed

Huang, Joanne; D'Souza, Ajit J; Alarcon, Jason B; Mikszta, John A; Ford, Brandi M; Ferriter, Matthew S; Evans, Michelle; Stewart, Todd; Amemiya, Kei; Ulrich, Robert G; Sullivan, Vincent J

2009-05-01

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V fusion protein of Y. pestis for vaccination against plaque in a mouse model. Mice were immunized with reconstituted spray-freeze-dried F1-V powder via intramuscular injection, microneedle-based intradermal delivery, or noninvasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against lethal subcutaneous challenge with 1,000 50% lethal doses of Y. pestis at levels equivalent to those elicited by unprocessed liquid formulations (70 to 90% protection). The feasibility of intradermal and intranasal delivery of reconstituted powder F1-V vaccine was also demonstrated. Overall, microneedle-based intradermal delivery was shown to be similar in efficacy to intramuscular injection, while intranasal administration required an extra dose of vaccine to achieve similar protection. In addition, the results suggest that seroconversion against F1 may be a better predictor of protection against Y. pestis challenge than seroconversion against either F1-V or V. In summary, we demonstrate the preclinical feasibility of using a reconstituted powder F1-V formulation and microneedle-based intradermal delivery to provide protective immunity against plague in a mouse model. Intranasal delivery, while feasible, was less effective than injection in this study. The potential use of these alternative delivery methods and a powder vaccine formulation may result in substantial health and economic benefits.

Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting.

PubMed

Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J Michael; Kanerva, Anna; Hemminki, Akseli

2016-05-01

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8(+) T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors.

Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting

PubMed Central

Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J. Michael; Kanerva, Anna; Hemminki, Akseli

2016-01-01

ABSTRACT Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8+ T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors. PMID:27467954

The effects of topical sodium cromoglicate on itch and flare in human skin induced by intradermal histamine: a randomised double-blind vehicle controlled intra-subject design trial

PubMed Central

2011-01-01

Background Itch is a prominent feature of many skin diseases, particularly atopic dermatitis and cutaneous mastocytosis. Sodium cromoglicate (SCG), a chromone developed for the treatment of allergic disease has been shown to reduce the severity of itch when applied topically to subjects with atopic dermatitis. The aim of this study was to investigate whether topical sodium cromoglicate can reduce the severity of itch induced by intradermal histamine. Methods SCG was introduced into the skin of healthy volunteers both by iontophoresis and by topical application using a new 4% cutaneous emulsion (Altoderm™). The skin was then challenged with intradermal histamine. Measurements were made of severity of itch, size of wheal and flare and change in blood flux Results SCG significantly reduced the severity of itch (P = 0.0045) and flare (P = 0.0143) when delivered by iontophoresis. SCG 4% cutaneous emulsion significantly reduced severity of itch (P = 0.024) and flare (P = 0.015) in atopic subjects. Trend analysis showed increasing effect on itch with increased concentrations of SCG, which was significant (P = 0.046). There were no effects on wheal or blood flux. Conclusions Topically applied SCG, administered in a new cutaneous emulsion base, significantly reduced the itch and flare caused by intradermal histamine. The effect was greatest in atopic subjects and increased with the concentration of SCG in the emulsion. Trial registration ISRCTN35671014 PMID:21385340

Topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial.

PubMed

Hung, Ivan Fan-Ngai; Zhang, Anna Jinxia; To, Kelvin Kai-Wang; Chan, Jasper Fuk-Woo; Li, Patrick; Wong, Tin-Lun; Zhang, Ricky; Chan, Tuen-Ching; Chan, Brian Chun-Yuan; Wai, Harrison Ho; Chan, Lok-Wun; Fong, Hugo Pak-Yiu; Hui, Raymond Kar-Ching; Kong, Ka-Lun; Leung, Arthur Chun-Fung; Ngan, Abe Ho-Ting; Tsang, Louise Wing-Ki; Yeung, Alex Pat-Chung; Yiu, Geo Chi-Ngo; Yung, Wing; Lau, Johnson Y-N; Chen, Honglin; Chan, Kwok-Hung; Yuen, Kwok-Yung

2016-02-01

Pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. We aimed to clarify its effect in a younger age group. In this double-blind, randomised controlled trial, we enrolled healthy volunteers aged 18-30 years in early 2014 to receive the 2013-14 northern-hemisphere winter trivalent influenza vaccine at the Queen Mary Hospital, (Hong Kong, China). Eligible participants were randomly assigned (1:1:1:1) to one of the four vaccination groups: the study group, topical imiquimod-cream followed by intradermal trivalent influenza vaccine (INF-Q-ID), or one of three control groups, topical aqueous-cream control followed by intradermal trivalent influenza vaccine (INF-C-ID), topical aqueous-cream control followed by intramuscular trivalent influenza vaccine (INF-C-IM), and topical imiquimod-cream followed by intradermal normal-saline injection (SAL-Q-ID). Randomisation was by computer-generated lists in blocks of four. The type of topical treatment was masked from volunteers and investigators, although not from the study nurse. Serum haemagglutination-inhibition and microneutralisation-antibody titres were assayed. The primary outcome was seroconversion at day 7 after treatment for three vaccine strains of influenza (A/California/07/2009 H1N1-like virus [A/California/H1N1], A/Victoria/361/2011 H3N2-like virus [A/Victoria/H3N2], and B/Massachusetts/2/2012-like virus [B/Yamagata lineage]) and four non-vaccine strains (A/HK/485197/14 [H3N2 Switzerland-like lineage], prototype A/WSN/1933 [H1N1], A/HK/408027/09 [prepandemic seasonal H1N1], and B/HK/418078/11 [Victoria lineage]). Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02103023. We enrolled 160 healthy volunteers between March 1 and May 31, 2014, and 40 participants were randomly assigned to each study group. For the A/California/H1N1 strain

Lentinan: hematopoietic, immunological, and efficacy studies in a syngeneic model of acute myeloid leukemia.

PubMed

McCormack, Emmet; Skavland, Jørn; Mujic, Maja; Bruserud, Øystein; Gjertsen, Bjørn Tore

2010-01-01

Lentinan, a beta-glucan nutritional supplement isolated from the shitake mushroom (Lentula edodes), is a biological response modifier with immunostimulatory properties. Concomitantly, the role of beta-glucans as chemoimmunotherapeutic in a number of solid cancers has been widely documented. We investigated the effects of nutritional grade lentinan upon BN rats and in a preclinical syngeneic model of acute myeloid leukemia. BN rats supplemented daily with lentinan exhibited weight gains, increased white blood cells, monocytes, and circulating cytotoxic T-cells; and had a reduction in anti-inflammatory cytokines IL-4, IL-10, and additionally IL-6. Lentinan treatment of BN rats with BNML leukemia resulted in improved cage-side health and reduced cachexia in the terminal stage of this aggressive disease. Combination of lentinan with standards of care in acute myeloid leukemia, idarubicin, and cytarabine increased average survival compared with monotherapy and reduced cachexia. These results indicate that nutritional supplementation of cancer patients with lentinan should be further investigated.

Protective effect of intradermal BCG against leprosy; a case-control study in central Brazil.

PubMed

Rodrigues, M L; Silva, S A; Neto, J C; de Andrade, A L; Martelli, C M; Zicker, F

1992-09-01

A case-control study was undertaken to evaluate the protective efficacy of intradermal BCG against leprosy in a high-endemic area of leprosy in central Brazil. Sixty-two cases and 186 controls were included in the study. Cases were all newly diagnosed leprosy patients under 16 years of age attending an outpatient health service, and all of them were schoolchildren. Three controls under 16 years old, frequency matched by sex and age group, were selected from schools geographically located in the area from which the cases came. The presence of BCG was negatively associated with leprosy, indicating a 5.3 risk of leprosy for those nonvaccinated and protective efficacy of 81%. Paucibacillary patients were more likely to have a BCG scar than multibacillary patients.

Expanded experience with an intradermal skin test to predict for the presence or absence of carboplatin hypersensitivity.

PubMed

Markman, Maurie; Zanotti, Kristine; Peterson, Gertrude; Kulp, Barbara; Webster, Kenneth; Belinson, Jerome

2003-12-15

Carboplatin-associated hypersensitivity is increasingly recognized as a potentially serious toxicity when this agent is administered for more than six total cycles. Our group has used a predictive skin test in women with gynecologic cancers who have previously received more than six cumulative cycles of platinum-based chemotherapy. Thirty minutes before all subsequent carboplatin courses, a 0.02-mL aliquot from the solution prepared for treatment is injected intradermally. A positive test is considered to be a > or = 5-mm wheal, with a surrounding flare. From October 1998 through March 2003, 126 patients received a total of 717 carboplatin skin tests (median per patient, four tests; range, one to 54 tests). Of the 668 negative tests (93% of the total performed), 10 were associated with evidence of carboplatin hypersensitivity (1.5% false-negative rate; 95% CI, 0.6% to 2.4%), none of which were severe (eg, dyspnea, hypotension, cardiac/respiratory compromise). Of the 41 positive tests, the decision was made to not deliver the drug to 32 patients, although seven women ultimately underwent a future attempt at re-treatment with a platinum agent using a desensitization program. In seven episodes where patients received the carboplatin despite the finding of a positive test, six were associated with the development of symptoms of anaphylaxis (none severe). A negative carboplatin skin test seems to predict with reasonable reliability for the absence of a severe hypersensitivity reaction with the subsequent drug infusion. The implications of a positive test remain less certain, but limited experience with continued treatment suggests this approach must be undertaken with considerable caution.

Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model.

PubMed

Akiyama, Tasuku; Carstens, Mirela Iodi; Carstens, E

2011-06-01

Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.

Efficient intradermal delivery of superoxide dismutase using a combination of liposomes and iontophoresis for protection against UV-induced skin damage.

PubMed

Kigasawa, Kaoru; Miyashita, Moeko; Kajimoto, Kazuaki; Kanamura, Kiyoshi; Harashima, Hideyoshi; Kogure, Kentaro

2012-01-01

Superoxide dismutase (SOD) is a potent antioxidant agent that protects against UV-induced skin damage. However, its high molecular weight is a significant obstacle for efficient delivery into the skin through the stratum corneum and development of antioxidant activity. Recently, we developed a non-invasive transfollicular delivery system for macromolecules using a combination of liposomes and iontophoresis, that represents promising technology for enhancing transdermal administration of charged drugs (IJP, 403, 2011, Kajimoto et al.). In this study, in rats we attempted to apply this system to intradermal delivery of SOD for preventing UV-induced skin injury. SOD encapsulating in cationic liposomes was subjected to anodal iontophoresis. After iontophoretic treatment, the liposomes were diffused widely in the viable skin layer around hair follicles. In contrast, passive diffusion failed to transport liposomes efficiently into the skin. Iontophoretic delivery of liposomes encapsulating SOD caused a marked decrease in the production of oxidative products, such as malondialdehyde, hexanoyl lysine, and 8-hydroxi-2-deoxyguanosine, in UV-irradiated skin. These findings suggested that functional SOD can be delivered into the skin using a combination of iontophoresis and a liposomal system. In conclusion, we succeeded in developing an efficient intradermal SOD delivery system, that would be useful for delivery of other macromolecules.

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.

Sex differences in the MB49 syngeneic, murine model of bladder cancer.

PubMed

White-Gilbertson, Shai; Davis, Megan; Voelkel-Johnson, Christina; Kasman, Laura M

The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro . MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro . The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice.

[Autoantibody formation against the antigens of the synaptonemal complex in the syngeneic immunization of male Mus musculus].

PubMed

Dadashev, S Ia; Gorach, G G; Kolomiets, O L

1994-01-01

Male mice were immunized with the suspension of synaptonemal complexes (SC) isolated from mouse spermatocytes nuclei. The indirect immunofluorescent analysis showed the active binding of sera obtained from immunized mice to SC of mouse spermatocyte spreads. At early and mid-pachytene, SC can be clearly identified in 19 autosome bivalents and in sex chromosome bivalent. According to the electron microscopic analysis, all structural elements of SC bind antibodies. Metaphase chromosomes were not stained with the immune sera. Specificity of interaction between SC components and antibodies was confirmed in a series of control experiments. Analysis of sera obtained from mice after their syngeneic immunization with isolated SC fraction suggested that certain mouse SC components induce the formation of autoantibodies. This, in turn, suggests that these SC components are meiosis-specific.

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

PubMed

Azzarito, Tommaso; Lugini, Luana; 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.

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

Local Expression of Indoleamine 2,3 Dioxygenase in Syngeneic Fibroblasts Significantly Prolongs Survival of an Engineered Three-Dimensional Islet Allograft

PubMed Central

Jalili, Reza B.; Forouzandeh, Farshad; Rezakhanlou, Alireza Moeen; Hartwell, Ryan; Medina, Abelardo; Warnock, Garth L.; Larijani, Bagher; Ghahary, Aziz

2010-01-01

OBJECTIVE The requirement of systemic immunosuppression after islet transplantation is of significant concern and a major drawback to clinical islet transplantation. Here, we introduce a novel composite three-dimensional islet graft equipped with a local immunosuppressive system that prevents islet allograft rejection without systemic antirejection agents. In this composite graft, expression of indoleamine 2,3 dioxygenase (IDO), a tryptophan-degrading enzyme, in syngeneic fibroblasts provides a low-tryptophan microenvironment within which T-cells cannot proliferate and infiltrate islets. RESEARCH DESIGN AND METHODS Composite three-dimensional islet grafts were engineered by embedding allogeneic mouse islets and adenoviral-transduced IDO–expressing syngeneic fibroblasts within collagen gel matrix. These grafts were then transplanted into renal subcapsular space of streptozotocin diabetic immunocompetent mice. The viability, function, and criteria for graft take were then determined in the graft recipient mice. RESULTS IDO-expressing grafts survived significantly longer than controls (41.2 ± 1.64 vs. 12.9 ± 0.73 days; P < 0.001) without administration of systemic immunesuppressive agents. Local expression of IDO suppressed effector T-cells at the graft site, induced a Th2 immune response shift, generated an anti-inflammatory cytokine profile, delayed alloantibody production, and increased number of regulatory T-cells in draining lymph nodes, which resulted in antigen-specific impairment of T-cell priming. CONCLUSIONS Local IDO expression prevents cellular and humoral alloimmune responses against islets and significantly prolongs islet allograft survival without systemic antirejection treatments. This promising finding proves the potent local immunosuppressive activity of IDO in islet allografts and sets the stage for development of a long-lasting nonrejectable islet allograft using stable IDO induction in bystander fibroblasts. PMID:20522587

Respiratory allergy to Blomia tropicalis: Immune response in four syngeneic mouse strains and assessment of a low allergen-dose, short-term experimental model

PubMed Central

2010-01-01

, immunization with a relatively low BtE dose (10 μg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose BtE immunization, for the development of allergy-associated immune and lung inflammatory responses. Conclusions The described short-term model of BtE-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and BtE induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of BtE. PMID:20433763

Effects of hyperthermia and calcium channel blocker co-therapy on mice injected with Meth A solid of Meth A ascites tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prince, R.N.

1986-01-01

A study was made to determine the effectiveness of treating tumor-injected mice with verapamil, a calcium antagonist, and hyperthermia. The co-treatment reduced the incidence of tumors in animals injected with Meth A solid cells. It was shown that the decrease in tumors corresponded to increases in natural killer (NK) cell activity measured in a /sup 51/Cr release assay, in the amount of anti-Meth A antibody measured in an immunofluorescence assay, and a decrease in the amount of intra-tumor cyclic AMP measured by radioimmunoassay in co-treated compared to untreated sarcoma-injected animals. A role of the immune system for mediating the preventionmore » of sarcoma growth was indicated by Winn assays. Splenocytes sensitized in vivo against Meth A solid cells for 14 days exhibited an enhanced cytotoxic activity against syngeneic target cells compared to untreated tumor-sensitized splenocytes following heat-drug co-treatment. It was established that the stimulation of cytotoxic T cells against a histocompatibility antigen (H-2/sup d/) present on Meth A sarcoma cells resulted in tumor cell lysis. Animals bearing established Meth A solid sarcomas did not manifest tumor regressions following the administration of co-treatment alone or the adoptive transfer of co-treated tumor-sensitized splenocytes. The growth of Meth A ascites and Meth A ascites-derived solid sarcomas, unlike Meth A solid cell tumors, were not prevented in Winn assays. Additionally, the lifespan of animals injected with Meth A ascites cells was reduced by 50% compared to animals injected with Meth A solid sarcoma cells.« less

Intralesional botulinum toxin-A injection for the treatment of multiple eccrine hidrocystomas.

PubMed

Gheisari, Mehdi; Hamedani, Behnaz; Robati, RezaM; Mozafari, Nikoo

2018-01-31

Multiple eccrine hidrocystomas (MEH) are benign cystic lesions of the sweat gland ducts. They are characterized by translucent, skin-colored or bluish dome-shaped papules on the face, causing cosmetic concern. Recently, botulinum toxin-A, because of its antiperspirant properties, has been used to treat facial MEH. However, there are only some case reports in the literature. Here, we conducted a prospective study to assess the efficacy and safety of intralesional injection of botulinum toxin-A (Dysport) for the treatment of MEH. Twenty patients (3 men and 17 women), aged from 31 to 75 years old, participated in this study. A 300 unit vial of botulinum toxin-A (Dysport, Ipsenn Biopharm, United Kingdom) was diluted with 4 ml of saline solution without preservative to achieve a concentration of 7.5U/.1 ml. Up to 1.5 unit of botulinum toxin was injected intradermally at the base of each lesion to raise a visible wheal. The patients were evaluated 7 days later, and any clinical changes or adverse effects were recorded. In all patients, more than 75% of eccrine hidrocystoma lesions resolved without any scaring. The result sustained for 2-5 months. In two patients mild smile asymmetry and in one patient lagophthalmos were noted approximately 5-7 days after injection that gradually resolved in 3 weeks. Intralesional botulinum toxin-A for treatment of multiple hidrocystomas is a simple and well-tolerated procedure. It is accompanied by excellent results, a good postoperative course, and no risk of scarring. It can be considered in patients who did not respond to other treatment or even as the first line therapy.

Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model

PubMed Central

Akiyama, Tasuku; Carstens, Mirela Iodi

2011-01-01

Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors. PMID:21430273

Age-related changes in localization of injected radiolabelled lymphocytes in the lymph nodes of antigen-stimulated mice.

PubMed Central

Inchley, C J; Micklem, H S; Barrett, J; Hunter, J; Minty, C

1976-01-01

The localization of i.v. injected syngeneic lymph node cells, radiolabelled with 51Cr or 75Se-L-selenomethionine, was studied in male CBA/H mice aged between 3 and 30 months. The following results were obtained. (1) Localization of cells from young adult donors was greater in the s.c. lymph nodes of old than of young recipients, the main increase being between 15 and 17 months of age. Increases in lymph node weight and DNA-synthesis were also seen at this time; but the rise in cell localization was significant even when calculated per unit of tissue weight. Splenic localization either declined slightly with age or, like the liver, showed no significant change. (2) Local antigenic stimulation by a single injection of sheep erythrocytes into one front footpad, 24 hr before lymph node cell injection, resulted in increased localization in the regional lymph nodes of 3-17 month old, but rarely of 24-30 month old mice. (3) No consistent differences in localization were observed between lymph node cells from 4-month and 25-month old donors. Both age-related and antigen-related increases in cell localization were at least partly attributable to an enhanced rate of entry of lymphocytes from the blood to the lymph nodes. Although the changes underlying the decline in antigen-related localization of cells in old recipients have still to be clarified, it is probable that the defective immune responses of old mice result partly from this decline. PMID:991459

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

Sex differences in the MB49 syngeneic, murine model of bladder cancer

PubMed Central

White-Gilbertson, Shai; Davis, Megan; Voelkel-Johnson, Christina; Kasman, Laura M.

2016-01-01

OBJECTIVE The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). METHODS Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro. RESULTS MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro. CONCLUSIONS The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice. PMID:26998503

Comparison of volume, security, and biomechanical strength of square and Aberdeen termination knots tied with 4-0 polyglyconate and used for termination of intradermal closures in canine cadavers.

PubMed

Regier, Penny J; Smeak, Daniel D; Coleman, Kristin; McGilvray, Kirk C

2015-08-01

To compare volumes of square knots and Aberdeen knots in vitro and evaluate security of these knot types when used as buried terminal knots for continuous intradermal wound closures in canine cadavers. Experimental study. 24 surgically closed, full-thickness, 4-cm, epidermal wounds in 4 canine cadavers and 80 knots tied in vitro. Continuous intradermal closures were performed with 4-0 polyglyconate and completed with a buried knot technique. Surgeon (intern or experienced surgeon) and termination knot type (4-throw square knot or 2 + 1 Aberdeen knot; 12 each) were randomly assigned. Closed wounds were excised, and 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, and mode of construct failure were recorded. Volumes of 2 + 1 Aberdeen (n = 40) and 4-throw square knots (40) tied on a suture board were measured on the basis of a cylindrical model. Aberdeen knots had a mean smaller volume (0.00045 mm(3)) than did square knots (0.003838 mm(3)). Maximum load and displacement did not differ between construct types. Mean stiffness of Aberdeen knot constructs was greater than that of square knots. The 2 + 1 Aberdeen knot had a smaller volume than the 4-throw square knot and was as secure. Although both knots may be reliably used in a clinical setting as the termination knot at the end of a continuous intradermal line, the authors advocate use of the Aberdeen terminal knot on the basis of ease of burying the smaller knot.

Comparison of intradermal dilutional testing, skin prick testing, and modified quantitative testing for common allergens.

PubMed

Peltier, Jacques; Ryan, Matthew W

2007-08-01

To compare and correlate wheal size using the Multi-Test II applicator with the endpoint obtained by intradermal dilutional testing (IDT) for 5 common allergens. To examine the safety of modified quantitative testing (MQT) for determining immunotherapy starting doses. Prospective comparative clinical study. A total of 134 subjects were simultaneously skin tested for immediate hypersensitivity using the Multi-Test II device and IDT. There was a 77% concordance between results from IDT and results from MQT. When there was a difference, MQT predicted a safer endpoint for starting immunotherapy in all but 2 cases. Wheal size by SPT is predictive of endpoint by IDT. MQT is nearly as effective as formal IDT in determining endpoint. Modified quantitative testing appears to be a safe alternative to IDT for determining starting doses for immunotherapy.

The activity of mouse Kupffer cells following intravenous injection of T4 bacteriophage

PubMed Central

Inchley, C. J.

1969-01-01

The response of macrophages from the livers and spleens of mice given a single immunizing dose of T4 bacteriophage has been studied. Following their rapid removal from the circulation, phage particles were found to be concentrated in the liver to a level twelve times that for the spleen. Investigation of the fate of ingested phage showed that it was disposed of more rapidly in the liver than in the spleen, as measured by the disappearance of viable T4 particles and by the loss of radioactive label following injection of [131I]T4. It was also found that antigen-containing Kupffer cells could elicit little or no antibody synthesis on transfer into normal syngeneic recipients, or on incubation with lymphoid cells in vitro. It is suggested that these macrophages differ from other components of the reticulo-endothelial system in their treatment of T4 antigen, and may be concerned mainly with its breakdown and disposal rather than with providing a stimulus for the initiation of antibody synthesis. PMID:5370053

The proliferative response of cloned Peyer's patch switch T cells to syngeneic and allogeneic stimuli.

PubMed

Kawanishi, H; Ozato, K; Strober, W

1985-06-01

We previously defined a concanavalin A (Con A)-induced cloned T cell population in Peyer's patches (PP) that causes sIgM-bearing B cells to switch to sIgA-bearing B cells. In the present study we show that such IgA-specific switch T cells proliferate when exposed to syngeneic stimulator cells, i.e., the switch T cells are autoreactive. Detailed study of this phenomenon disclosed that both B cells and macrophages were capable of causing switch T cell proliferation, and in both cases, stimulation was enhanced by preactivation of the stimulator cells with lipopolysaccharide (LPS). In addition, fresh T cells can act as stimulators, but only if preactivated with Con A. Finally, it was clearly shown in blocking studies with the use of various antibodies directed at class II MHC specificities that class II MHC antigens were the stimulatory determinants. These studies suggest that IgA-specific switch T cells arise in PP as a result of autologous cell-cell interactions with activated (antigen-stimulated) B cells, macrophages, or T cells.

Area 3a Neuron Response to Skin Nociceptor Afferent Drive

PubMed Central

Favorov, Oleg V.; Li, Yongbiao; Quibrera, Miguel; Tommerdahl, Mark

2009-01-01

Area 3a neurons are identified that respond weakly or not at all to skin contact with a 25–38 °C probe, but vigorously to skin contact with the probe at ≥49 °C. Maximal rate of spike firing associated with 1- to 7-s contact at ≥49 °C occurs 1-2 s after probe removal from the skin. The activity evoked by 5-s contact with the probe at 51 °C remains above-background for ∼20 s after probe retraction. After 1-s contact at 55–56 °C activity remains above-background for ∼4 s. Magnitude of spike firing associated with 5-s contact increases linearly as probe temperature is increased from 49–51 °C. Intradermal capsaicin injection elicits a larger (∼2.5×) and longer-lasting (100×) increase in area 3a neuron firing rate than 5-s contact at 51 °C. Area 3a neurons exhibit enhanced or novel responsivity to 25–38 °C contact for a prolonged time after intradermal injection of capsaicin or α, β methylene adenosine triphosphate. Their 1) delayed and persisting increase in spike firing in response to contact at ≥49 °C, 2) vigorous and prolonged response to intradermal capsaicin, and 3) enhanced and frequently novel response to 25–38 °C contact following intradermal algogen injection or noxious skin heating suggest that the area 3a neurons identified in this study contribute to second pain and mechanical hyperalgesia/allodynia. PMID:18534992

Cholera toxin B-subunit gene enhances mucosal immunoglobulin A, Th1-type, and CD8+ cytotoxic responses when coadministered intradermally with a DNA vaccine.

PubMed

Sanchez, Alba E; Aquino, Guillermo; Ostoa-Saloma, Pedro; Laclette, Juan P; Rocha-Zavaleta, Leticia

2004-07-01

A plasmid vector encoding the cholera toxin B subunit (pCtB) was evaluated as an intradermal genetic adjuvant for a model DNA vaccine expressing the human papillomavirus type 16 L1 capsid gene (p16L1) in mice. p16L1 was coadministered with plasmid pCtB or commercial polypeptide CtB as a positive control. Coadministration of pCtB induced a significant increment of specific anti-L1 immunoglobulin A (IgA) antibodies in cervical secretions (P < 0.05) and fecal extracts (P < 0.005). Additionally, coadministration of pCtB enhanced the production of interleukin-2 and gamma interferon by spleen cells but did not affect the production of interleukin-4, suggesting a Th1-type helper response. Furthermore, improved CD8+ T-cell-mediated cytotoxic activity was observed in mice vaccinated with the DNA vaccine with pCtB as an adjuvant. This adjuvant effect was comparable to that induced by the CtB polypeptide. These results indicate that intradermal coadministration of pCtB is an adequate means to enhance the mucosa-, Th1-, and CD8(+)-mediated cytotoxic responses induced by a DNA vaccine.

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.

Cost-effectiveness of an influenza vaccination program offering intramuscular and intradermal vaccines versus intramuscular vaccine alone for elderly.

PubMed

Leung, Man-Kit; You, Joyce H S

2016-05-11

Intradermal (ID) injection is an alternative route for influenza vaccine administration in elderly with potential improvement of vaccine coverage. This study aimed to investigate the cost-effectiveness of an influenza vaccination program offering ID vaccine to elderly who had declined intramuscular (IM) vaccine from the perspective of Hong Kong public healthcare provider. A decision analytic model was used to simulate outcomes of two programs: IM vaccine alone (IM program), and IM or ID vaccine (IM/ID program) in a hypothetic cohort of elderly aged 65 years. Outcome measures included influenza-related direct medical cost, infection rate, mortality rate, quality-adjusted life years (QALYs) loss, and incremental cost per QALY saved (ICER). Model inputs were derived from literature. Sensitivity analyses evaluated the impact of uncertainty of model variables. In base-case analysis, the IM/ID program was more costly (USD52.82 versus USD47.59 per individual to whom vaccine was offered) with lower influenza infection rate (8.71% versus 9.65%), mortality rate (0.021% versus 0.024%) and QALYs loss (0.00336 versus 0.00372) than the IM program. ICER of IM/ID program was USD14,528 per QALY saved. One-way sensitivity analysis found ICER of IM/ID program to exceed willingness-to-pay threshold (USD39,933) when probability of influenza infection in unvaccinated elderly decreased from 10.6% to 5.4%. In 10,000 Monte Carlo simulations of elderly populations of Hong Kong, the IM/ID program was the preferred option in 94.7% of time. An influenza vaccination program offering ID vaccine to elderly who had declined IM vaccine appears to be a highly cost-effective option. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fibromodulin deficiency reduces collagen structural network but not glycosaminoglycan content in a syngeneic model of colon carcinoma.

PubMed

Olsson, P Olof; Kalamajski, Sebastian; Maccarana, Marco; Oldberg, Åke; Rubin, Kristofer

2017-01-01

Tumor barrier function in carcinoma represents a major challenge to treatment and is therefore an attractive target for increasing drug delivery. Variables related to tumor barrier include aberrant blood vessels, high interstitial fluid pressure, and the composition and structure of the extracellular matrix. One of the proteins associated with dense extracellular matrices is fibromodulin, a collagen fibrillogenesis modulator expressed in tumor stroma but scarce in normal loose connective tissues. Here, we investigated the effects of fibromodulin on stroma ECM in a syngeneic murine colon carcinoma model. We show that fibromodulin deficiency decreased collagen fibril thickness but glycosaminoglycan content and composition were unchanged. Furthermore, vascular density, pericyte coverage and macrophage amount were unaffected. Fibromodulin can therefore be a unique effector of dense collagen matrix assembly in tumor stroma and, without affecting other major matrix components or the cellular composition, can function as a main agent in tumor barrier function.

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine.

PubMed

Morse, Kaitlyn; Kimizuka, Yoshifumi; Chan, Megan P K; Shibata, Mai; Shimaoka, Yusuke; Takeuchi, Shu; Forbes, Benjamin; Nirschl, Christopher; Li, Binghao; Zeng, Yang; Bronson, Roderick T; Katagiri, Wataru; Shigeta, Ayako; Sîrbulescu, Ruxandra F; Chen, Huabiao; Tan, Rhea Y Y; Tsukada, Kosuke; Brauns, Timothy; Gelfand, Jeffrey; Sluder, Ann; Locascio, Joseph J; Poznansky, Mark C; Anandasabapathy, Niroshana; Kashiwagi, Satoshi

2017-08-15

Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates that the NIR laser adjuvant has the capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. In this study we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations. We found that a continuous wave (CW) NIR laser adjuvant broadly modulates migratory DC (migDC) populations, specifically increasing and activating the Lang + and CD11b - Lang - subsets in skin, and that the Ab responses augmented by the CW NIR laser are dependent on DC subsets expressing CCR2 and Langerin. In comparison, a pulsed wave NIR laser adjuvant showed limited effects on the migDC subsets. Our vaccination study demonstrated that the efficacy of the CW NIR laser is significantly better than that of the pulsed wave laser, indicating that the CW NIR laser offers a desirable immunostimulatory microenvironment for migDCs. These results demonstrate the unique ability of the NIR laser adjuvant to selectively target specific migDC populations in skin depending on its parameters, and highlight the importance of optimization of laser parameters for desirable immune protection induced by an NIR laser-adjuvanted vaccine. Copyright © 2017 by The American Association of Immunologists, Inc.

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.

Capsaicin did not evoke pain from human hand vein segments but did so after injections into the paravascular tissue.

PubMed

Arndt, J O; Kindgen-Milles, D; Klement, W

1993-04-01

1. To see if pain from veins is mediated by C fibre endings, the C fibre stimulant capsaicin was applied intravenously, and, for comparison, paravenously and intracutaneously. 2. Capsaicin, dissolved in the fat emulsion Intralipid, was applied intravenously by continuous perfusion of vascularly isolated hand vein segments as well as by injections into occluded finger veins. Using the latter approach chemicals reach the paravascular space. 3. Pain intensities were recorded continuously with an electronically controlled visual analogue scale for deriving capsaicin concentration-pain intensity relations and the time course of pain (latencies, pain durations). 4. Capsaicin always evoked pain upon injection into skin and paravenous tissue (0.3-6.5 microM) and into occluded finger veins (3.3-33 microM), whereas it had no effect whatsoever when perfused through hand vein segments even at a concentration of 650 microM. 5. Pain intensity increased with concentration and usually reached the tolerance maximum at the fivefold threshold concentration, so that the concentration-pain intensity relations were congruent for the various routes of drug application. 6. The latencies and pain durations were independent of the capsaicin concentration, but were substantially longer with injections into occluded finger veins (latency 10-30 s, pain duration 60-120 s) than with intradermal or paravenous injections (2-9 s, 10-28 s). 7. These observations show for the first time a functional similarity between the nociceptive C fibre system of the skin and the paravascular tissues, and by inference, they dismiss the possibility that C fibre endings mediate pain in cutaneous veins.

Job Language Performance Requirements for MOS 91C, Clinical Specialist, Reference Soldier’s Manual Dated 30 August 1977.

DTIC Science & Technology

1977-08-30

Administer a rectal suppository 081-91C-1240 Administer an injection (SC or IM) 081-91C-1241 Administer an intradermal injection 081-91C-1242 Administer a...in this language task: Shouting Radio communications Coded messages Spellings Conversation Requests wI-3 SPEAKING *TASK: Formulate and produce

A study for characterization of IgE-mediated cutaneous immediate and late-phase reactions in non-allergic domestic cats.

PubMed

Seals, Shanna L; Kearney, Michael; Del Piero, Fabio; Hammerberg, Bruce; Pucheu-Haston, Cherie M

2014-05-15

Immunoglobulin-E (IgE) mediated reactions can be induced by intradermal injection of anti-IgE antibodies in both humans and dogs. These reactions grossly and histologically mimic changes seen in naturally occurring allergic dermatitis in these species. Similar studies have not been conducted in the cat. Purified polyclonal rabbit-origin IgG specific for canine IgE (anti-IgE) and rabbit immunoglobulin G (IgG) were injected intradermally in 7 non-allergic laboratory colony cats. Wheal measurements were obtained and biopsies collected before injection and at injection sites after 20 min, 6, 24, and 48 h. Injection of anti-IgE induced an immediate wheal response which was significantly larger than that seen after injection of rabbit IgG. Anti-IgE injected skin was also significantly thicker than IgG-injected skin. This corresponded with a significant increase in number of visibly degranulated mast cells in anti-IgE samples when compared to IgG samples. Injection of anti-IgE was associated with the rapid recruitment of inflammatory cells to the injected dermis. The number of inflammatory cells and mononuclear cells were significantly elevated after the injection of anti-IgE when compared to IgG-injected skin. Both eosinophils and neutrophils were significantly increased in anti-IgE samples relative to IgG, although neutrophils were only transiently increased. The high eosinophil and relatively low neutrophil cell counts in these samples were consistent with previously documented histologic features of naturally occurring feline allergic skin disease. Immunohistochemistry identified a significantly overall increased CD1a(+) cells after the intradermal injection of anti-IgE when compared to IgG and non-injected skin. CD3(+), CD8(+) and CD4(+) were also significantly increased overall in anti-IgE injected skin relative to IgG injected skin. These data document the gross and cellular response to injection of anti-IgE in the skin of healthy, non-allergic cats and support a

Immunologic responses against hydrolyzed soy protein in dogs with experimentally induced soy hypersensitivity.

PubMed

Puigdemont, Anna; Brazís, Pilar; Serra, Montserrat; Fondati, Alessandra

2006-03-01

To assess whether dogs with experimentally induced type I hypersensitivity against soy protein would respond to soy hydrolysate and develop cutaneous or gastrointestinal tract reactions after intradermal and oral challenge exposure. 12 naïve Beagle pups (9 sensitized and 3 control dogs). 9 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization period, serum concentrations of soy-specific IgE were determined and an intradermal test was performed to confirm the dogs were sensitized against soy protein. An intradermal challenge test and an oral challenge test with native and hydrolyzed soy protein were conducted on 6 sensitized and 2 control dogs. High serum concentrations of soy-specific IgE and positive results for the intradermal test were observed for the 9 sensitized dogs after completion of the sesitization process. Sensitized dogs challenge exposed with hydrolyzed soy protein had a reduced inflammatory response after intradermal injection and no clinical response after an oral challenge exposure, compared with responses after intradermal and oral challenge exposure with native soy protein. Soy-sensitized dogs did not respond to oral administration of hydrolyzed soy protein. Thus, hydrolyzed soy protein may be useful in diets formulated for the management of dogs with adverse reactions to food.

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

Avoiding and treating dermal filler complications.

PubMed

Lemperle, Gottfried; Rullan, Peter P; Gauthier-Hazan, Nelly

2006-09-01

All fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of and accept these risks. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., too superficial an implantation of a long-lasting filler substance). Such adverse events can be treated with intradermal 5-fluorouracil, steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunologic phenomena such as late-onset allergy and nonallergic foreign body granuloma. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions shall remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granuloma in the subcutaneous fat.

The infiltration of experimentally induced lung metastases of colon carcinoma CC531 by adoptively transferred interleukin-2-activated natural killer cells in Wag rats.

PubMed

Kuppen, P J; Basse, P H; Goldfarb, R H; Van De Velde, C J; Fleuren, G J; Eggermont, A M

1994-02-15

The number of IL-2-activated natural killer (A-NK) cells reaching the tumor site in vivo may be crucial for their anti-tumor effect following adoptive immunotherapy. We investigated in a syngeneic rat model the infiltration of established lung metastases by adoptively transferred A-NK cells. The Wag rat colon carcinoma CC531 was injected via a tail vein to induce pulmonary metastases. Syngeneic A-NK cells were labeled with the fluorescent dye rhodamine (TRITC) and next injected via a tail vein in rats bearing day-12 lung tumors. The number of A-NK cells in tumor and in normal tissue per rat was counted in sections after administration of A-NK cells. At all time points tested, a significant linear relationship between the cross-section area of the tumor and the number of infiltrating cells was observed, but small tumor areas became fully infiltrated earlier than larger areas. At 24 hr after injection, approximately 10% of the injected cells were found in the tumor tissue and the average A-NK-cell-to-tumor-cell ratio was estimated to be 1:3. A-NK cells were found in the liver too, although the number of cells per mm2 tissue was low compared with the pulmonary tumor tissue. Very low numbers of A-NK cells were found in kidney, adrenal gland, spleen, and blood. We conclude that, in this syngeneic rat model, adoptively transferred A-NK cells are able to find and specifically infiltrate pulmonary metastases in a time-dependent fashion.

Minipigs as an Animal Model for Dermal Vaccine Delivery

PubMed Central

Ploemen, Ivo HJ; Hirschberg, Hoang JHB; Kraan, Heleen; Zeltner, Adrian; van Kuijk, Sandra; Lankveld, Danielle PK; Royals, Michael; Kersten, Gideon FA; Amorij, Jean-Pierre

2014-01-01

Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery. Here we describe the immunization of Göttingen minipigs by using intradermal and intramuscular delivery of hepatitis B surface antigen (HBsAg). Intradermal vaccine delivery by needle and syringe and by needle-free jet injection induced humoral antiHBsAg responses. Priming immunization by using the disposable syringe jet injector (DSJI) resulted in a higher antibody titer than did conventional intradermal immunization and a titer comparable to that after intramuscular vaccination with HBsAg and Al(OH)3 adjuvant. This study highlights the utility of the minipig model in vaccine studies assessing the efficacy of conventional and novel methods of dermal delivery. Moreover, we include suggestions regarding working with minipigs during dermal vaccine delivery studies, thereby fostering future work in this area of vaccinology. PMID:24512961

Immune response in domestic ducks following intradermal delivery of inactivated vaccine against H5N1 highly pathogenic avian influenza virus adjuvanted with oligodeoxynucleotides containing CpG motifs.

PubMed

Yuk, Seong-Su; Lee, Dong-Hun; Park, Jae-Keun; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Gomis, Susantha; Song, Chang-Seon

2015-08-01

Ducks are a natural reservoir for H5N1 highly pathogenic avian influenza (HPAI) viruses, which produces a range of clinical outcomes from asymptomatic infections to severe disease with mortality. Vaccination against HPAI is one of the few methods available for controlling avian influenza virus (AIV) infection in domestic ducks; therefore, it is necessary to improve vaccine efficacy against HPAI in domestic ducks. However, few studies have focused on enhancing the immune response by testing alternative administration routes and adjuvants. While attempting to maximize the efficacy of a vaccine, it is important to select an appropriate vaccine delivery route and adjuvant to elicit an enhanced immune response. Although several studies have indicated that the vaccination of ducks against HPAI viruses has offered protection against lethal virus challenge, the immunogenicity of the vaccine still requires improvement. In this study, we characterized the immune response following a novel vaccination strategy against H5N1 HPAI virus in domestic ducks. Our novel intradermal delivery system and the application of the cytosine-phosphodiester-guanine (CpG) oligodeoxynucleotide (ODN) adjuvant allowed us to obtain information regarding the sustained vaccine immunity. Compared with the intramuscular route of vaccination, the intradermal route resulted in higher antibody titer as well as lower antibody deviation following secondary vaccination. In addition, the use of a CpG-ODN adjuvant had a dose-sparing effect on antibody titer. Furthermore, when a high dose of antigen was used, the CpG-ODN-adjuvanted vaccine maintained a high mean antibody titer. This data demonstrates that intradermal immunization combined with administration of CpG-ODN as an adjuvant may be a promising strategy for improving vaccine efficacy in domestic ducks. © 2015 Poultry Science Association Inc.

Transient engraftment of syngeneic bone marrow after conditioning with high-dose cyclophosphamide and thoracoabdominal irradiation in a patient with aplastic anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsue, K.; Niki, T.; Shiobara, S.

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 somemore » cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.« less

Cell-mediated T lymphocyte responses against syngeneic cells modified with amino-reactive hapten (AED-NH2): H-2Dk serves as an element for cell-mediated lympholysis to amino-reactive hapten (AED-NH2)-modified self.

PubMed

Mizuochi, T; Fujiwara, H; Takai, Y; Hamaoka, T

1985-02-01

Spleen cells from C3H/He mice immunized to the newly synthesized amino-reactive hapten, 5-sulfo-1-naphthoxy acetic acid N-hydroxysuccinimide (AED-NH2), were stimulated in vitro with AED-NH2 modified syngeneic cells. After 5 days of culture, effector cells were assayed for their cytotoxic activity against AED-NH2-modified target blast cells. In contrast to other amino-reactive haptens reported so far, a strong cytotoxic activity against AED-NH2-modified syngeneic cells was found in H-2b mice as well as in H-2k mice. Furthermore, Dk-restricted anti-AED-NH2 CTL recognition was observed in H-2k mice as shown by cold target inhibition. Previous studies have demonstrated the predominant influence of K over D region self determinants, and of the chemical reactivity of the haptenic reagent in Ir gene control of CTL response to hapten-self. The present report illustrates the importance of the hapten itself in genetic regulation of these CTL responses.

Nine μg intradermal influenza vaccine and 15 μg intramuscular influenza vaccine induce similar cellular and humoral immune responses in adults

PubMed Central

Nougarede, Nolwenn; Bisceglia, Hélène; Rozières, Aurore; Goujon, Catherine; Boudet, Florence; Laurent, Philippe; Vanbervliet, Beatrice; Rodet, Karen; Hennino, Ana; Nicolas, Jean-François

2014-01-01

Intanza® 9 μg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 μg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 μg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 μg (n = 38) or IM 15 μg (n = 42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 μg vaccine are similar to those to the standard IM 15 μg vaccine. PMID:25483667

Nine μg intradermal influenza vaccine and 15 μg intramuscular influenza vaccine induce similar cellular and humoral immune responses in adults.

PubMed

Nougarede, Nolwenn; Bisceglia, Hélène; Rozières, Aurore; Goujon, Catherine; Boudet, Florence; Laurent, Philippe; Vanbervliet, Beatrice; Rodet, Karen; Hennino, Ana; Nicolas, Jean-François

2014-01-01

Intanza® 9 μg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 μg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 μg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 μg (n=38) or IM 15 μg (n=42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 μg vaccine are similar to those to the standard IM 15 μg vaccine.

Impact on caesarean section rates following injections of sterile water (ICARIS): a multicentre randomised controlled trial.

PubMed

Lee, Nigel; Mårtensson, Lena B; Homer, Caroline; Webster, Joan; Gibbons, Kristen; Stapleton, Helen; Dos Santos, Natalie; Beckmann, Michael; Gao, Yu; Kildea, Sue

2013-05-03

Sterile water injections have been used as an effective intervention for the management of back pain during labour. The objective of the current research is to determine if sterile water injections, as an intervention for back pain in labour, will reduce the intrapartum caesarean section rate. A double blind randomised placebo controlled trialSetting: Maternity hospitals in AustraliaParticipants: 1866 women in labour, ≥18 years of age who have a singleton pregnancy with a fetus in a cephalic presentation at term (between 37 + 0 and 41 + 6 weeks gestation), who assess their back pain as equal to or greater than seven on a visual analogue scale when requesting analgesia and able to provide informed consent. Participants will be randomised to receive either 0.1 to 0.3 millilitres of sterile water or a normal saline placebo via four intradermal injections into four anatomical points surrounding the Michaelis' rhomboid over the sacral area. Two injections will be administered over the posterior superior iliac spine (PSIS) and the remaining two at two centimetres posterior, and one centimetre medial to the PSIS respectively. Proportion of women who have a caesarean section in labour.Randomisation: Permuted blocks stratified by research site.Blinding (masking):Double-blind trial in which participants, clinicians and research staff blinded to group assignment. Funded by the National Health and Medical Research CouncilTrial registration:Australian New Zealand Clinical Trials Registry (No ACTRN12611000221954). Sterile water injections, which may have a positive effect on reducing the CS rate, have been shown to be a safe and simple analgesic suitable for most maternity settings. A procedure that could reduce intervention rates without adversely affecting safety for mother and baby would benefit Australian families and taxpayers and would reduce requirements for maternal operating theatre time. Results will have external validity, as the technique may be easily applied to

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.

Influence of reserpine on in vivo localization of injected lymph node cells in the mouse.

PubMed Central

Bellavia, A; Micklem, H S

1987-01-01

The effects of reserpine, and other agents that affect the storage and availability of 5-hydroxytryptamine (5HT), on the localization of injected 51Cr-labelled syngeneic lymph node cells have been investigated. A high dose (5 mg/kg) of reserpine to the recipients reduced localization in the lymph nodes and prevented the usual accumulation of lymphocytes in lymph nodes draining the site of an antigen (sheep erythrocytes: SE) injection. These effects were partially reversible by the monoamine oxidase inhibitor nialamide. This dose of reserpine produced deep sedation throughout the period of the experiment. Lower doses, up to 2.5 mg/kg, produced little sedation and had no effect on the localization of lymphocytes. Other workers had previously reported reduced localization of cells in delayed-type hypersensitivity (DTH) lesions after treatment of the recipients with 5 mg/kg reserpine, and had interpreted this in terms of a role of 5HT in promoting vascular permeability and egress of blood cells. The effect of lower doses of reserpine was not reported. We suggest that the effects on cell localization in both sets of experiments may have been secondary to the general state of sedation and not attributable to a direct local influence of 5HT. Other effects of reserpine included prolonged retention of lymphocytes in lungs and blood, and a reduction of cellularity and DNA synthesis in the thymus, spleen and lymph nodes. PMID:3817871

Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy.

PubMed

Machado, Yoan; Duinkerken, Sanne; Hoepflinger, Veronika; Mayr, Melissa; Korotchenko, Evgeniia; Kurtaj, Almedina; Pablos, Isabel; Steiner, Markus; Stoecklinger, Angelika; Lübbers, Joyce; Schmid, Maximillian; Ritter, Uwe; Scheiblhofer, Sandra; Ablinger, Michael; Wally, Verena; Hochmann, Sarah; Raninger, Anna M; Strunk, Dirk; van Kooyk, Yvette; Thalhamer, Josef; Weiss, Richard

2017-11-28

Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14 + dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

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

A double-blind, placebo-controlled study of preventive immunotherapy with E.P.D., in the treatment of seasonal allergic disease.

PubMed

Di Stanislao, C; Di Berardino, L; Bianchi, I; Bologna, G

1997-02-01

Control of seasonal symptoms by means of a preventive and easy to use (only one intradermal injection eight weeks before the pollen peak) immunotherapy, is recommended nowadays. We verified the clinical efficacy of E.P.D. (Enzyme Potentiated Desensibilization) in a double-blind, placebo-controlled study. This particular immunotherapy consists of an intradermal injection mix, made up of allergenic extracts at extremely low doses and an enzyme called beta-glucuronidase. The vaccine is administered once a year, eight weeks before pollen peaks. We studied a group of 40 patients allergic to grass pollen. The results, analysed statistically on the basis of a symptoms score, showed good clinical efficacy and a significant reduction of drug consumption during the high pollen period. Due to the clinical effectiveness, easy administration (only on injection) and excellent tolerance of the immunotherapy, E.P.D. is particularly suited for the prevention of seasonal symptoms in patients allergic to grass pollen.

Self-Assembly DNA Polyplex Vaccine inside Dissolving Microneedles for High-Potency Intradermal Vaccination.

PubMed

Liao, Jing-Fong; Lee, Jin-Ching; Lin, Chun-Kuang; Wei, Kuo-Chen; Chen, Pin-Yuan; Yang, Hung-Wei

2017-01-01

The strong immunogenicity induction is the powerful weapon to prevent the virus infections. This study demonstrated that one-step synthesis of DNA polyplex vaccine in microneedle (MN) patches can induce high immunogenicity through intradermal vaccination and increase the vaccine stability for storage outside the cold chain. More negative charged DNA vaccine was entrapped into the needle region of MNs followed by DNA polyplex formation with branched polyethylenimine (bPEI) pre-coated in the cavities of polydimethylsiloxane (PDMS) molds that can deliver more DNA vaccine to immune-cell rich epidermis with high transfection efficiency. Our data in this study support the safety and immunogenicity of the MN-based vaccine; the MN patch delivery system induced an immune response 3.5-fold as strong as seen with conventional intramuscular administration; the DNA polyplex formulation provided excellent vaccine stability at high temperature (could be stored at 45ºC for at least 4 months); the DNA vaccine is expected to be manufactured at low cost and not generate sharps waste. We think this study is significant to public health because there is a pressing need for an effective vaccination in developing countries.

Concordance between peri-areolar blue dye and peri-incisional radiotracer injections for sentinel node mapping in patients with a history of primary breast cancer excisonal biopsy.

PubMed

Mehrabibahar, M; Azizi, S; Jangjoo, A; Saremi, E; Kakhki, V R Dabbagh; Sadeghi, R; Chicken, D W; Keshtgar, M

2014-01-01

We evaluated the concordance between peri-areolar blue dye and peri-incisional radiotracer injections for axillary sentinel node mapping of patients with the history of previous breast lesion excisional biopsy. 80 patients with the history of previous excisional biopsy of the breast lesions were included. All patients received two injections of 99mTc-antimony sulfide colloid in both ends of incision line in an intradermal fashion. 2 mL patient blue V dye was injection to all patients in the peri-areolar area of the index quadrant after induction of anesthesia. All blue or hot nodes were harvested as sentinel lymph nodes. At least one sentinel node could be detected during surgery in 79 patients. In total 94 sentinel nodes were detected. All detected sentinel nodes were hot. In three patients sentinel nodes were detected by gamma probe but not blue dye. The tumor location in all of these patients was in the upper lateral quadrant and the incision line was extended into the axillary tail of the breast in all of them. 91 out of 94 sentinel nodes were stained blue, which amounts to 95.8% concordance between blue dye and radiotracer on a per node analysis. Single peri-areolar injection in the index quadrant would suffice for sentinel node mapping of patients with history of excisional biopsy. Care should be taken in patients with large excisional biopsy in the extreme proximity to axilla.

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

A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods.

PubMed

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

2008-04-23

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. 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. 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. 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 introduced without further studies. Controlled

Feasibility of sustainable provision of intradermal post exposure prophylaxis against rabies at primary care level –evidence from rural Haryana

PubMed Central

2014-01-01

Background Rabies is the most severe and neglected public health problem in India. Management of animal bite with post exposure prophylaxis is the only existent strategy to prevent rabies related deaths. Cost-effective and sustainable programme for provision of post exposure prophylaxis (PEP) is needed in India. Methods In this study, we have documented the experience of implementation of intra-dermal anti rabies vaccination in Animal Bite Management (ABM) clinic at Primary Health Centre (PHC). This study facility belonged to Comprehensive Rural Health Services Project, Ballabgarh in Faridabad district of Haryana. Hospital service record of ABM clinic was analyzed and various feasibility issues such as costing of services, vaccine wastage and other operational issues in providing PEP services at PHC level were documented. Results A total of 619 patients were treated in the ABM clinic. Service utilization of ABM clinic was increased by 38% in the second year of implementation. Mean age of the patients was 23.9 years (SD: 18.8) and majority (70.4%) were males. Majority (86%) of the patients received the first dose of anti-rabies vaccine within the recommended 48 hours. A total 446 vaccine vials (1 ml) were consumed of which 20.8% was contributed in vaccine wastage. User-fee (350 Indian Rupees) collected from the patients. User-fee was re-used to purchase vaccines, intradermal (ID) syringes and other consumables required to ensure regular availability of ARV services at the PHC. Conclusions This study demonstrated the cost-effective and sustainable model of provision of PEP against rabies at primary care level. ID PEP provision at primary care level not only address the unmet need of animal bite management in the community also reduces the out of pocket expenditure of the patients. PMID:24965875

Development and psychometric validation of a self-administered questionnaire assessing the acceptance of influenza vaccination: the Vaccinees' Perception of Injection (VAPI©) questionnaire

PubMed Central

Chevat, Catherine; Viala-Danten, Muriel; Dias-Barbosa, Carla; Nguyen, Van Hung

2009-01-01

Background Influenza is among the most common infectious diseases. The main protection against influenza is vaccination. A self-administered questionnaire was developed and validated for use in clinical trials to assess subjects' perception and acceptance of influenza vaccination and its subsequent injection site reactions (ISR). Methods The VAPI questionnaire was developed based on interviews with vaccinees. The initial version was administered to subjects in international clinical trials comparing intradermal with intramuscular influenza vaccination. Item reduction and scale construction were carried out using principal component and multitrait analyses (n = 549). Psychometric validation of the final version was conducted per country (n = 5,543) and included construct and clinical validity and internal consistency reliability. All subjects gave their written informed consent before being interviewed or included in the clinical studies. Results The final questionnaire comprised 4 dimensions ("bother from ISR"; "arm movement"; "sleep"; "acceptability") grouping 16 items, and 5 individual items (anxiety before vaccination; bother from pain during vaccination; satisfaction with injection system; willingness to be vaccinated next year; anxiety about vaccination next year). Construct validity was confirmed for all scales in most of the countries. Internal consistency reliability was good for all versions (Cronbach's alpha ranging from 0.68 to 0.94), as was clinical validity: scores were positively correlated with the severity of ISR and pain. Conclusion The VAPI questionnaire is a valid and reliable tool, assessing the acceptance of vaccine injection and reactions following vaccination. Trial registration NCT00258934, NCT00383526, NCT00383539. PMID:19261173

Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

PubMed Central

Gerull, Sabine; Stern, Martin; Apperley, Jane; Beelen, Dietrich; Brinch, Lorentz; Bunjes, Donald; Butler, Andrew; Ganser, Arnold; Ghavamzadeh, Ardeshir; Koh, Mickey B; Komarnicki, Mieczyslaw; Kröger, Nicolaus; Maertens, Johan; Maschan, Alexei; Peters, Christina; Rovira, Montserrat; Sengeløv, Henrik; Socié, Gerard; Tischer, Johanna; Oneto, Rosi; Passweg, Jakob; Marsh, Judith

2013-01-01

Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source. PMID:23894010

Intanza® 9 µg intradermal seasonal influenza vaccine for adults 18 to 59 years of age

PubMed Central

Leroux-Roels, Isabel; Weber, Françoise

2013-01-01

Seasonal influenza in healthy working-age adults accounts for a substantial part of the socioeconomic burden of this disease. Intanza® 9 μg (sanofi pasteur) is a microneedle-delivered intradermal trivalent inactivated influenza vaccine approved in 2009 for the prevention of seasonal influenza in adults 18 to 59 y of age. The microneedle system reliably and reproducibly delivers the vaccine to the dermis. Clinical studies show that Intanza 9 μg is as immunogenic and as well tolerated in working-age adults as a reference intramuscular trivalent inactivated vaccine. Local reactions to Intanza 9 μg, mainly erythema, are transient, mostly mild or moderate, and do not affect acceptability. Intanza 9 μg is considered satisfactory by at least 95% of both vaccinees and prescribers, especially because of the short needle and rapid administration. Because Intanza® 9 μg offers an alternative to intramuscular vaccines, it might help increase influenza vaccine coverage rates. PMID:23442585

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

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

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. 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. 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. 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. International Standard Randomised Controlled Trial Number (ISRCTN) 60284968.

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

Flow cytometric analysis of regulatory T cells during hyposensitization of acquired allergic contact dermatitis.

PubMed

Fraser, Kathleen; Abbas, Mariam; Hull, Peter R

2014-01-01

We previously demonstrated that repeated intradermal steroid injections administered at weekly intervals into positive patch-test sites induce hyposensitization and desensitization. To examine changes in CD4CD25CD127lo/ regulatory T cells during the attenuation of the patch-test response. Ten patients with known allergic contact dermatitis were patch tested weekly for 10 weeks. The patch-test site was injected intradermally with 2 mg triamcinolone. At weeks 1 and 7, a biopsy was performed on the patch-test site in 6 patients, and flow cytometry was performed assessing CD4CD25CD127lo/ regulatory T cells. Secondary outcomes were clinical score, reaction size, erythema, and temperature. Statistical analysis included regression, correlation, and repeated-measures analysis of variance. The percentage of CD4CD25CD127lo/ regulatory T cells, measured by flow cytometry, increased from week 1 to week 7 by an average of 19.2%. The average grade of patch-test reaction decreased from +++ (vesicular reaction) to ++ (palpable erythema). The mean drop in temperature following treatment was 0.28°C per week. The mean area decreased 8.6 mm/wk over 10 weeks. Intradermal steroid injections of weekly patch-test reactions resulted in hyposensitization of the allergic contact dermatitis reaction. CD4CD25CD127lo/ regulatory T cells showed a tendency to increase; however, further studies are needed to determine if this is significant.

Hepatitis B revaccination in healthy non-responder Chinese children: five-year follow-up of immune response and immunologic memory.

PubMed

Zhuang, Gui-Hua; Yan, Hong; Wang, Xue-Liang; Hwang, Lu-Yu; Wu, Qian; Wang, Li-Rong; Gao, Hai-Yan

2006-03-15

To assess persistence of anti-HBs and immunologic memory of non-responders after revaccination, 40 healthy non-responder children were given a three-dose recombinant hepatitis B vaccine revaccination randomly by intramuscular (10 microg per dose) or intradermal (2 microg per dose) route and followed up to five years. All 17 intramuscular and 22 of 23 intradermal children developed a seroprotective antibody response (anti-HBs>or=10 mIU/mL) after revaccination. Children of intramuscular group had significantly higher seroprotection rates and anti-HBs geometric mean titers than the intradermal group. At year 5, 50% of children in intramuscular group, but only 18.2% of intradermal group still maintained seroprotection (P=0.075). By the end of follow-up, a booster dose (5 microg) was given to those who had lost seroprotection. All the eight intramuscular children developed an anamnestic response with increase of anti-HBs level by 215 times, but two of the 18 intradermal children failed to produce seroprotective level. Three-routine-dose intramuscular revaccination was significantly more effective than low-dose intradermal revaccination with the same number of injections. No child seroconverted to HBsAg, and 11 had transient infections indicated by seroconversion to anti-HBc. These results demonstrated that non-responders could benefit from three doses intramuscular revaccination not only in high proportion of anti-HBs conversion but also in long-term persistence of seroprotection, and more importantly in preservation of the immunologic memory years after loss of protective anti-HBs.

Investigating skin penetration depth and shape following needle-free injection at different pressures: A cadaveric study.

PubMed

Seok, Joon; Oh, Chang Taek; Kwon, Hyun Jung; Kwon, Tae Rin; Choi, Eun Ja; Choi, Sun Young; Mun, Seog Kyun; Han, Seung-Ho; Kim, Beom Joon; Kim, Myeung Nam

2016-08-01

The effectiveness of needle-free injection devices in neocollagenesis for treating extended skin planes is an area of active research. It is anticipated that needle-free injection systems will not only be used to inject vaccines or insulin, but will also greatly aid skin rejuvenation when used to inject aesthetic materials such as hyaluronic acid, botulinum toxin, and placental extracts. There has not been any specific research to date examining how materials penetrate the skin when a needle-free injection device is used. In this study, we investigated how material infiltrates the skin when it is injected into a cadaver using a needle-free device. Using a needle-free injector (INNOJECTOR™; Amore Pacific, Seoul, Korea), 0.2 ml of 5% methylene blue (MB) or latex was injected into cheeks of human cadavers. The device has a nozzle diameter of 100 µm and produces a jet with velocity of 180 m/s. This jet penetrates the skin and delivers medicine intradermally via liquid propelled by compressed gasses. Materials were injected at pressures of 6 or 8.5 bars, and the injection areas were excised after the procedure. The excised areas were observed visually and with a phototrichogram to investigate the size, infiltration depth, and shape of the hole created on the skin. A small part of the area that was excised was magnified and stained with H&E (×40) for histological examination. We characterized the shape, size, and depth of skin infiltration following injection of 5% MB or latex into cadaver cheeks using a needle-free injection device at various pressure settings. Under visual inspection, the injection at 6 bars created semi-circle-shaped hole that penetrated half the depth of the excised tissue, while injection at 8.5 bars created a cylinder-shaped hole that spanned the entire depth of the excised tissue. More specific measurements were collected using phototrichogram imaging. The shape of the injection entry point was consistently spherical regardless of the

Polidocanol injection for chemical delay and its effect on the survival of rat dorsal skin flaps.

PubMed

Menevşe, Gülsüm Tetik; TeomanTellioglu, Ali; Altuntas, Nurgül; Cömert, Ayhan; Tekdemir, Ibrahim

2014-06-01

Surgical delay is an invasive method requiring a two-stage surgical procedure. Hence, methods that may serve as an alternative to surgical delay have become the focus of interest of research studies. From a conceptual view, any technique that interrupts the blood flow along the edges of a proposed flap will render the flap ischemic and induce a delay phenomenon. Polidocanol (Aethoxysklerol(®)-Kreussler) was initially used as a local anesthetic. Nowadays, it has been used as a sclerosing agent to treat telangiectasias and varicose veins. The aim of this experimental study was to investigate the effects of polidocanol injected around the periphery of a random flap as a sclerosing agent on flap delay and survival in a random flap model. A preliminary histopathologic study was performed on two rats to evaluate the sclerosing effect and distribution of polidocanol injection. After the preliminary study, the main study was carried out with three groups: group 1: dorsal flap (n = 10); group 2: dorsal flap + surgical delay (n = 10), group 3: dorsal flap + chemical delay (n = 10). Tissue samples obtained from the flap and injection area revealed destruction of intradermal vessels. The area affected with sclerosis was limited to 0.1 cm beyond the injection site. Mean viable flap areas were 52.1 ± 4.38% (44.0-58.2) in group 1, 64.8 ± 8.92% (57.2-89.2) in group 2, and 71.8 ± 5.18% (64.0-84.0) in group 3. A statistically highly significant difference was found between the surgical delay and chemical delay groups versus the group without delay (p < 0.001 and p < 0.001, respectively). The difference between the mean viable flap areas was not statistically significant in the surgical and chemical delay groups (p = 0.056). In conclusion, this study has shown that polidocanol injection around the dorsal flap in the rat is a safe and easy method for nonsurgical delay. The results have shown a flap survival benefit that is superior to controls and equivalent to surgical delay. The

Alternative vaccine administration by powder injection: Needle-free dermal delivery of the glycoconjugate meningococcal group Y vaccine

PubMed Central

Schiffter, Heiko A.; Carlisle, Robert C.; Rollier, Christine S.; Prud’homme, Robert K.; Pollard, Andrew J.

2017-01-01

Powder-injectors use gas propulsion to deposit lyophilised drug or vaccine particles in the epidermal and sub epidermal layers of the skin. We prepared dry-powder (Tg = 45.2 ± 0.5°C) microparticles (58.1 μm) of a MenY-CRM197 glyconjugate vaccine (0.5% wt.) for intradermal needle-free powder injection (NFPI). SFD used ultrasound atomisation of the liquid vaccine-containing excipient feed, followed by lyophilisation above the glass transition temperature (Tg’ = − 29.9 ± 0.3°C). This resulted in robust particles (density~ 0.53 ±0.09 g/cm3) with a narrow volume size distribution (mean diameter 58.1 μm, and span = 1.2), and an impact parameter (ρvr ~ 11.5 kg/m·s) sufficient to breach the Stratum corneum (sc). The trehalose, manitol, dextran (10 kDa), dextran (150 kDa) formulation, or TMDD (3:3:3:1), protected the MenY-CRM197 glyconjugate during SFD with minimal loss, no detectable chemical degradation or physical aggregation. In a capsular group Y Neisseria meningitidis serum bactericidal assay (SBA) with human serum complement, the needle free vaccine, which contained no alum adjuvant, induced functional protective antibody responses in vivo of similar magnitude to the conventional vaccine injected by hypodermic needle and syringe and containing alum adjuvant. These results demonstrate that needle-free vaccination is both technically and immunologically valid, and could be considered for vaccines in development. PMID:28837693

Doxil Synergizes with Cancer Immunotherapies to Enhance Antitumor Responses in Syngeneic Mouse Models

PubMed Central

Rios-Doria, Jonathan; Durham, Nicholas; Wetzel, Leslie; Rothstein, Raymond; Chesebrough, Jon; Holoweckyj, Nicholas; Zhao, Wei; Leow, Ching Ching; Hollingsworth, Robert

2015-01-01

Based on the previously described roles of doxorubicin in immunogenic cell death, both doxorubicin and liposomal doxorubicin (Doxil) were evaluated for their ability to boost the antitumor response of different cancer immunotherapies including checkpoint blockers (anti–PD-L1, PD-1, and CTLA-4 mAbs) and TNF receptor agonists (OX40 and GITR ligand fusion proteins) in syngeneic mouse models. In a preventative CT26 mouse tumor model, both doxorubicin and Doxil synergized with anti–PD-1 and CTLA-4 mAbs. Doxil was active when CT26 tumors were grown in immunocompetent mice but not immunocompromised mice, demonstrating that Doxil activity is increased in the presence of a functional immune system. Using established tumors and maximally efficacious doses of Doxil and cancer immunotherapies in either CT26 or MCA205 tumor models, combination groups produced strong synergistic antitumor effects, a larger percentage of complete responders, and increased survival. In vivo pharmacodynamic studies showed that Doxil treatment decreased the percentage of tumor-infiltrating regulatory T cells and, in combination with anti–PD-L1, increased the percentage of tumor-infiltrating CD8+ T cells. In the tumor, Doxil administration increased CD80 expression on mature dendritic cells. CD80 expression was also increased on both monocytic and granulocytic myeloid cells, suggesting that Doxil may induce these tumor-infiltrating cells to elicit a costimulatory phenotype capable of activating an antitumor T-cell response. These results uncover a novel role for Doxil in immunomodulation and support the use of Doxil in combination with checkpoint blockade or TNFR agonists to increase response rates and antitumor activity. PMID:26408258

Suppressive Effect of Immunization with Mouse Fetal Antigens on Growth of Cells Infected with Rauscher Leukemia Virus and on Plasma-Cell Tumors

PubMed Central

Hanna, M. G.; Tennant, R. W.; Coggin, J. H.

1971-01-01

The recovery of spleen cells infected with Rauscher leukemia virus (RLV) and grown in Millipore diffusion chambers, the development of RLV-induced splenomegaly, and the cumulative mortality from a transplanted ascites plasma-cell tumor were all suppressed in young adult BALB/c male mice previously primed at 3-weekly intervals with x-irradiated, syngeneic embryo cells. RLV-induced splenomegaly was also suppressed by adoptive transfer of postpartal spleen cells, as well as spleen cells for animals primed with syngeneic embryo cells. Similar suppressions were not observed in mice primed with neonatal or normal syngeneic cells. Further, injection of fetal cells was not effective in suppressing the immune function of normal spleen cells, as measured by ability to elaborate a primary immunoglobulin M response to heterologous erythrocyte antigen. The results of this study add to the broad spectrum of tumors of experimental animals and man known to contain neoantigens common to fetal cells. PMID:4942913

Development of an intradermal DNA vaccine delivery strategy to achieve single-dose immunity against respiratory syncytial virus.

PubMed

Smith, Trevor R F; Schultheis, Katherine; Morrow, Matthew P; Kraynyak, Kimberly A; McCoy, Jay R; Yim, Kevin C; Muthumani, Karuppiah; Humeau, Laurent; Weiner, David B; Sardesai, Niranjan Y; Broderick, Kate E

2017-05-15

Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, and an effective, safe RSV vaccine remains an unmet need. Here we assess a novel vaccination strategy based on the intradermal delivery of a SynCon® DNA-based vaccine encoding engineered RSV-F antigen using a surface electroporation device (SEP) to target epidermal cells, in clinically relevant experimental models. We demonstrate the ability of this strategy to elicit robust immune responses. Importantly we demonstrate complete resistance to pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A challenge model. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine, there was no enhanced lung inflammation upon virus challenge after DNA vaccination. In summary the data presented outline the pre-clinical development of a highly efficacious, tolerable and safe non-replicating vaccine delivery strategy. Copyright © 2017. Published by Elsevier Ltd.

Intradermal skin tests for rocuronium and cisatracurium in patients with a history of allergy: a retrospective study.

PubMed

Kim, Yu Yil; Kim, Ik Thae; Shin, Sung In; Yim, So Mang

2018-04-24

Neuromuscular blocking agents (NMBAs) are a leading cause of perioperative anaphylaxis. However, the performance of systematic screening skin tests to detect reactions for NMBAs prior to general anesthesia is not recommended. We retrospectively examined intradermal tests (IDTs) for rocuronium and cisatracurium in patients with a history of allergy. We reviewed the records of patients who underwent IDTs for NMBAs between January 1 and December 31, 2016. We analyzed the patients' allergy histories and skin test results for NMBAs. The overall prevalence of positive IDTs was 5.8% (26/451), and there was no significant difference in prevalence among allergy types (P = 0.655). In logistic regression analysis, there was no allergy history that had a significant effect on positive IDT for NMBAs. We found no association between allergy history and positive skin test for NMBAs. Therefore, a systematic screening test for NMBAs or other anesthetic agents before anesthesia is not considered necessary even in patients with an allergy history.

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

Accidental needle sticks, the Occupational Safety and Health Administration, and the fallacy of public policy.

PubMed

Wolf, Bruce L; Marks, Albert; Fahrenholz, John M

2006-07-01

Current Occupational Safety and Health Administration (OSHA) guidelines mandate the use of safety needles when allergy injections are given. Safety needles for intradermal testing remain optional. Whether safety needles reduce the number of accidental needle sticks (ANSs) in the outpatient setting has yet to be proven. To determine the rate of ANSs with new (safety) needles vs old needles used in allergy immunotherapy and intradermal testing. Allergy practices from 22 states were surveyed by e-mail. Seventy practices (28%) responded to the survey. Twice as many ANSs occurred in practices giving immunotherapy when using new needles vs old needles (P < .01). The rate of ANSs was roughly the same for intradermal testing with new needles vs old needles. These findings further question whether OSHA's guidelines for safety needle use in outpatient practice need revision and if allergy practices might be excluded from the requirement to use safety needles.

Intradermal immunisation using the TLR3-ligand Poly (I:C) as adjuvant induces mucosal antibody responses and protects against genital HSV-2 infection

PubMed Central

Bardel, Emilie; Doucet-Ladeveze, Remi; Mathieu, Cyrille; Harandi, Ali M; Dubois, Bertrand; Kaiserlian, Dominique

2016-01-01

Development of vaccines able to induce mucosal immunity in the genital and gastrointestinal tracts is a major challenge to counter sexually transmitted pathogens such as HIV-1 and HSV-2. Herein, we showed that intradermal (ID) immunisation with sub-unit vaccine antigens (i.e., HIV-1 gp140 and HSV-2 gD) delivered with Poly(I:C) or CpG1668 as adjuvant induces long-lasting virus-specific immunoglobulin (Ig)-G and IgA antibodies in the vagina and feces. Poly(I:C)-supplemented sub-unit viral vaccines caused minimal skin reactogenicity at variance to those containing CpG1668, promoted a delayed-type hypersensitivity (DTH) to the vaccine and protected mice from genital and neurological symptoms after a lethal vaginal HSV-2 challenge. Interestingly, Poly(I:C12U) (Ampligen), a Poly(I:C) structural analogue that binds to TLR3 but not MDA-5, promoted robust mucosal and systemic IgG antibodies, a weak skin DTH to the vaccine but not IgA responses and failed to confer protection against HSV-2 infection. Moreover, Poly(I:C) was far superior to Poly(I:C12U) at inducing prompt and robust upregulation of IFNß transcripts in lymph nodes draining the injection site. These data illustrate that ID vaccination with glycoproteins and Poly(I:C) as adjuvant promotes long-lasting mucosal immunity and protection from genital HSV-2 infection, with an acceptable skin reactogenicity profile. The ID route thus appears to be an unexpected inductive site for mucosal immunity and anti-viral protection suitable for sub-unit vaccines. This works further highlights that TLR3/MDA5 agonists such as Poly(I:C) may be valuable adjuvants for ID vaccination against sexually transmitted diseases. PMID:29263853

Soft fibrin gels promote selection and growth of tumorigenic cells

NASA Astrophysics Data System (ADS)

Liu, Jing; Tan, Youhua; Zhang, Huafeng; Zhang, Yi; Xu, Pingwei; Chen, Junwei; Poh, Yeh-Chuin; Tang, Ke; Wang, Ning; Huang, Bo

2012-08-01

The identification of stem-cell-like cancer cells through conventional methods that depend on stem cell markers is often unreliable. We developed a mechanical method for selecting tumorigenic cells by culturing single cancer cells in fibrin matrices of ~100 Pa in stiffness. When cultured within these gels, primary human cancer cells or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe combined immunodeficiency mice led to the formation of solid tumours at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as ten such cells were able to survive and form tumours in the lungs of wild-type non-syngeneic mice.

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

2017-12-01

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.

Post-exposure prophylaxis against rabies at two newly designated intradermal rabies vaccination clinics in Kerala, India.

PubMed

J, Teena M; Mathew, T; S, Anish T; M, Sujina C; Philip, R R

2012-01-01

The two-site intradermal rabies vaccination (IDRV) regimen was recently introduced in Kerala. We aimed to determine factors associated with exposure of category III severity among patients seeking prophylaxis against rabies at IDRV clinics. This hospital-based, cross-sectional study was done at two clinics in Thiruvananthapuram district, Kerala. Data were collected using a semi-structured questionnaire by direct interview and 320 patients were included. Bivariate analysis of quantitative variables was done using t-test and that of qualitative variables using chi-square test. The mean (standard deviation) age of patients was 32.4 (19.6) years. Among the 320 cases, 202 (63.1%) had category III exposure. Lower extremities were the most frequent site of exposure (146, 45.6%). The most frequent mode of exposure was being bitten by an animal (214, 66.9%), often a dog. Residence in rural areas, exposure to dogs and wounds on the extremities had a significant association with severity of exposure. Animal exposures were more among people from rural areas. About two-thirds of exposures which necessitated post-exposure prophylaxis were category III. Copyright 2012, NMJI.

High frequency ultrasound to assess skin thickness in healthy adults.

PubMed

Van Mulder, T J S; de Koeijer, M; Theeten, H; Willems, D; Van Damme, P; Demolder, M; De Meyer, G; Beyers, K C L; Vankerckhoven, V

2017-03-27

Intradermal immunization is gaining increased attention due to multiple factors: (1) intradermal (ID) vaccination has been shown to induce improved immunogenicity compared to intramuscular (IM) vaccination; (2) ID vaccination has been shown to have a dose-sparing potential over IM leading to a reduced vaccine cost and an increased availability of vaccines worldwide. However, the currently used Mantoux technique for ID injection is difficult to standardize and requires training. The aim of the study was (1) to assess the epidermal and dermal thickness at the proximal ventral and dorsal forearm (PVF & PDF) and deltoid in adults aged 18-65years (2) to determine the maximum penetration depth and needle characteristics for the development of a platform of medical devices suited for intradermal injection, VAX-ID™. Mean thickness of the PVF, PDF and deltoid were measured using high-frequency ultrasound of healthy adults aged 18-65years. Correlation with gender, age and BMI was assessed using Mann-Whitney U Test, Spearman correlation and Wilcoxon Signed Ranks Test, respectively. Results showed an overall mean skin thickness of 1.19mm (0.65-1.55mm) at the PVF, 1.44mm (0.78-1.84mm) at the PDF, and 2.12mm (1,16-3.19mm) at the deltoid. Thickness of PVF & PDF and deltoid were significantly different for men vs women (p mean <0.001, <0.001, <0.001, and p min <0.001, 0.012, <0.001, respectively). A significant association was found for age at the deltoid region (p<0.001). Skin thickness for PVF, PDF & deltoid was significantly associated to BMI (p<0.001). Significant differences in skin thickness were seen for the PVF, PDF and deltoid region for gender, and BMI. Age only influenced the skin thickness at deltoid region. A needle length of 1.0mm is best option for intradermal injection at the dorsal forearm (NCT02363465). Copyright © 2016 Elsevier Ltd. All rights reserved.

Rejection of syngeneic colon carcinoma by CTLs expressing single-chain antibody receptors codelivering CD28 costimulation.

PubMed

Haynes, Nicole M; Trapani, Joseph A; Teng, Michele W L; Jackson, Jacob T; Cerruti, Loretta; Jane, Stephen M; Kershaw, Michael H; Smyth, Mark J; Darcy, Phillip K

2002-11-15

A new strategy to improve the therapeutic utility of redirected T cells for cancer involves the development of novel Ag-specific chimeric receptors capable of stimulating optimal and sustained T cell antitumor activity in vivo. Given that T cells require both primary and costimulatory signals for optimal activation and that many tumors do not express critical costimulatory ligands, modified single-chain Ab receptors have been engineered to codeliver CD28 costimulation. In this study, we have compared the antitumor potency of primary T lymphocytes expressing carcinoembryonic Ag (CEA)-reactive chimeric receptors that incorporate either TCR-zeta or CD28/TCR-zeta signaling. Although both receptor-transduced T cell effector populations demonstrated cytolysis of CEA(+) tumors in vitro, T cells expressing the single-chain variable fragment of Ig (scFv)-CD28-zeta chimera had a far greater capacity to control the growth of CEA(+) xenogeneic and syngeneic colon carcinomas in vivo. The observed enhanced antitumor activity of T cells expressing the scFv-CD28-zeta receptor was critically dependent on perforin and the production of IFN-gamma. Overall, this study has illustrated the ability of a chimeric scFv receptor capable of harnessing the signaling machinery of both TCR-zeta and CD28 to augment T cell immunity against tumors that have lost expression of both MHC/peptide and costimulatory ligands in vivo.

FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model.

PubMed

Szymiczek, Agata; Pastorino, Sandra; Larson, David; Tanji, Mika; Pellegrini, Laura; Xue, Jiaming; Li, Shuangjing; Giorgi, Carlotta; Pinton, Paolo; Takinishi, Yasutaka; Pass, Harvey I; Furuya, Hideki; Gaudino, Giovanni; Napolitano, Andrea; Carbone, Michele; Yang, Haining

2017-03-15

Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy. The mechanism of action of FTY720 in MM was assessed by measuring the activity of phosphatase protein 2A (PP2A)-a major target of FTY720. The binding of the endogenous inhibitor SET to PP2A in presence of FTY720 was evaluated by immunoblotting and immunoprecipitation. Signaling and activation of programmed cell death were evaluated by immunoblotting and flow cytometry. A syngeneic mouse model was used to evaluate anti-tumor efficacy and toxicity profile of FTY720 in vivo. We show that FTY720 significantly suppressed MM cell viability and anchorage-independent growth without affecting normal HM cells. FTY720 inhibited the phosphatase activity of PP2A by displacement of SET protein, which appeared overexpressed in MM, as compared to HM cells. FTY720 promoted AKT dephosphorylation and Bcl-2 degradation, leading to induction of programmed cell death, as demonstrated by caspase-3 and PARP activation, as well as by cytochrome c and AIF intracellular translocation. Moreover, FTY720 administration in vivo effectively reduced tumor burden in mice without apparent toxicity. Our preclinical data indicate that FTY720 is a potentially promising therapeutic agent for MM treatment.

Comparison of the Immunogenicity and Safety of a Split-virion, Inactivated, Trivalent Influenza Vaccine (Fluzone®) Administered by Intradermal or Intramuscular Route in Healthy Adults

PubMed Central

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

2011-01-01

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 Systema), 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 6 μg 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

Live imaging of transforming growth factor-β activated kinase 1 activation in Lewis lung carcinoma 3LL cells implanted into syngeneic mice and treated with polyinosinic:polycytidylic acid.

PubMed

Takaoka, Saori; Kamioka, Yuji; Takakura, Kanako; Baba, Ai; Shime, Hiroaki; Seya, Tsukasa; Matsuda, Michiyuki

2016-05-01

Transforming growth factor-β activated kinase 1 (TAK1) has been shown to play a crucial role in cell death, differentiation, and inflammation. Here, we live-imaged robust TAK1 activation in Lewis lung carcinoma 3LL cells implanted into the s.c. tissue of syngeneic C57BL/6 mice and treated with polyinosinic:polycytidylic acid (PolyI:C). First, we developed and characterized a Förster resonance energy transfer-based biosensor for TAK1 activity. The TAK1 biosensor, named Eevee-TAK1, responded to stress-inducing reagents such as anisomycin, tumor necrosis factor-α, and interleukin1-β. The anisomycin-induced increase in Förster resonance energy transfer was abolished by the TAK1 inhibitor (5z)-7-oxozeaenol. Activity of TAK1 in 3LL cells was markedly increased by PolyI:C in the presence of macrophages. 3LL cells expressing Eevee-TAK1 were implanted into mice and observed through imaging window by two-photon excitation microscopy. During the growth of tumor, the 3LL cells at the periphery of the tumor showed higher TAK1 activity than the 3LL cells located at the center of the tumor, suggesting that cells at the periphery of the tumor mass were under stronger stress. Injection of PolyI:C, which is known to induce regression of the implanted tumors, induced marked and homogenous TAK1 activation within the tumor tissues. The effect of PolyI:C faded within 4 days. These observations suggest that Eevee-TAK1 is a versatile tool to monitor cellular stress in cancer tissues. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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

Modulation of human allogeneic and syngeneic pluripotent stem cells and immunological implications for transplantation.

PubMed

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

2016-04-01

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague

PubMed Central

Sebbane, Florent; Jarrett, Clayton O.; Gardner, Donald; Long, Daniel; Hinnebusch, B. Joseph

2006-01-01

Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread. PMID:16567636

Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague.

PubMed

Sebbane, Florent; Jarrett, Clayton O; Gardner, Donald; Long, Daniel; Hinnebusch, B Joseph

2006-04-04

Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread.

Characterization of the rhesus macaque (Macaca mulatta) scrub typhus model: Susceptibility to intradermal challenge with the human pathogen Orientia tsutsugamushi Karp

PubMed Central

Sunyakumthorn, Piyanate; Somponpun, Suwit J.; Im-erbsin, Rawiwan; Anantatat, Tippawan; Jenjaroen, Kemajittra; Dunachie, Susanna J.; Lombardini, Eric D.; Burke, Robin L.; Blacksell, Stuart D.; Jones, James W.; Mason, Carl J.; Richards, Allen L.; Day, Nicholas P. J.

2018-01-01

Background Scrub typhus is an important endemic disease in tropical Asia caused by Orientia tsutsugamushi for which no effective broadly protective vaccine is available. The successful evaluation of vaccine candidates requires well-characterized animal models and a better understanding of the immune response against O. tsutsugamushi. While many animal species have been used to study host immunity and vaccine responses in scrub typhus, only limited data exists in non-human primate (NHP) models. Methodology/Principle findings In this study we evaluated a NHP scrub typhus disease model based on intradermal inoculation of O. tsutsugamushi Karp strain in rhesus macaques (n = 7). After an intradermal inoculation with 106 murine LD50 of O. tsutsugamushi at the anterior thigh (n = 4) or mock inoculum (n = 3), a series of time course investigations involving hematological, biochemical, molecular and immunological assays were performed, until day 28, when tissues were collected for pathology and immunohistochemistry. In all NHPs with O. tsutsugamushi inoculation, but not with mock inoculation, the development of a classic eschar with central necrosis, regional lymphadenopathy, and elevation of body temperature was observed on days 7–21 post inoculation (pi); bacteremia was detected by qPCR on days 6–18 pi; and alteration of liver enzyme function and increase of white blood cells on day 14 pi. Immune assays demonstrated raised serum levels of soluble cell adhesion molecules, anti-O. tsutsugamushi-specific antibody responses (IgM and IgG) and pathogen-specific cell-mediated immune responses in inoculated macaques. The qPCR assays detected O. tsutsugamushi in eschar, spleen, draining and non-draining lymph nodes, and immuno-double staining demonstrated intracellular O. tsutsugamushi in antigen presenting cells of eschars and lymph nodes. Conclusions/Significance These data show the potential of using rhesus macaques as a scrub typhus model, for evaluation of correlates of

The effect of platelet-rich plasma on the outcome of short-term narrowband-ultraviolet B phototherapy in the treatment of vitiligo: a pilot study.

PubMed

Ibrahim, Zeinab A; El-Ashmawy, Amal A; El-Tatawy, Rania A; Sallam, Fersan A

2016-06-01

Narrowband - ultraviolet B (NB-UVB) is an emerging, effective, and safe therapy for vitiligo, but the treatment course often requires a long duration of time which may carry a potential risk for various side effects and patients' noncompliance. To explore the effect of platelet-rich plasma (PRP) injection on the outcome of short-term NB-UVB therapy for the patients with stable vitiligo. The study included 60 stable vitiligo patients with overall symmetrical lesions. For each patient, the left side of the body was treated with NB-UVB alone (control side) while the right side was treated with NB-UVB therapy in addition to intradermal injection of PRP, every 2 weeks for 4 months. There was statistically highly significant improvement in the repigmentation in the combination group(PRP plus NB-UVB) compared with NB-UVB group. Intradermal PRP injection in combination with NB-UVB could be considered as a simple, safe, tolerable, and cheap technique for treatment of vitiligo. It shortens the duration of NB-UVB therapy and is expected to increase patient compliance. Longer follow-up is needed. © 2015 Wiley Periodicals, Inc.

In vitro generation of helper T cells and suppressor T cells that regulate the cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells.

PubMed

Gualde, N; Weinberger, O; Ratnofsky, S; Benacerraf, B; Burakoff, S J

1982-04-01

Helper T cells and suppressor T cells have been generated in vitro that regulate the cytolytic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified syngeneic cells. B6D2F1 helper cells generated to TNP-modified parental (P1) cells augment the CTL response to those P1-TNP-modified antigens but not to P2-TNP-modified antigens. The generation of these helper T cells requires the presence of splenic adherent cells and these helper T cells are radioresistant. A soluble factor can be obtained from the helper T cell cultures that can also augment the CTL response. The suppressor T cells generated in culture do not demonstrate the specificity observed with the helper T cells; however, they are antigen-dependent in their induction. Whether helper or suppressor activity is obtained depends upon the length of time cells are cultured in vitro.

In vitro generation of helper T cells and suppressor T cells that regulate the cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gualde, N.; Weinberger, O.; Ratnofsky, S.

1982-04-01

Helper T cells and suppressor T cells have been generated in vitro that regulate the cytolytic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified syngeneic cells. B6D2F1 helper cells generated to TNP-modified parental (P1) cells augment the CTL response to those P1-TNP-modified antigens but not to P2-TNP-modified antigens. The generation of these helper T cells requires the presence of splenic adherent cells and these helper T cells are radioresistant. A soluble factor can be obtained from the helper T cell cultures that can also augment the CTL response. The suppressor T cells generated in culture do not demonstrate the specificity observedmore » with the helper T cells; however, they are antigen-dependent in their induction. Whether helper or suppressor activity is obtained depends upon the length of time cells are cultured in vitro.« less

Multimodality cellular and molecular imaging of concomitant tumour enhancement in a syngeneic mouse model of breast cancer metastasis.

PubMed

Parkins, Katie M; Dubois, Veronica P; Hamilton, Amanda M; Makela, Ashley V; Ronald, John A; Foster, Paula J

2018-06-12

The mechanisms that influence metastatic growth rates are poorly understood. One mechanism of interest known as concomitant tumour resistance (CTR) can be defined as the inhibition of metastasis by existing tumour mass. Conversely, the presence of a primary tumour has also been shown to increase metastatic outgrowth, termed concomitant tumour enhancement (CTE). The majority of studies evaluating CTR/CTE in preclinical models have relied on endpoint histological evaluation of tumour burden. The goal of this research was to use conventional magnetic resonance imaging (MRI), cellular MRI, and bioluminescence imaging to study the impact of a primary tumour on the development of brain metastases in a syngeneic mouse model. Here, we report that the presence of a 4T1 primary tumour significantly enhances total brain tumour burden in Balb/C mice. Using in vivo BLI/MRI we could determine this was not related to differences in initial arrest or clearance of viable cells in the brain, which suggests that the presence of a primary tumour can increase the proliferative growth of brain metastases in this model. The continued application of our longitudinal cellular and molecular imaging tools will yield a better understanding of the mechanism(s) by which this physiological inhibition (CTR) and/or enhancement (CTE) occurs.

Aedes mosquito saliva modulates Rift Valley fever virus pathogenicity.

PubMed

Le Coupanec, Alain; Babin, Divya; Fiette, Laurence; Jouvion, Grégory; Ave, Patrick; Misse, Dorothee; Bouloy, Michèle; Choumet, Valerie

2013-01-01

Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants. Mosquito saliva contains compounds that counteract the hemostatic, inflammatory, and immune responses of the host. Modulation of these defensive responses may facilitate virus infection. Indeed, Aedes mosquito saliva played a crucial role in the vector's capacity to effectively transfer arboviruses such as the Cache Valley and West Nile viruses. The role of mosquito saliva in the transmission of Rift Valley fever virus (RVFV) has not been investigated. Using a murine model, we explored the potential for mosquitoes to impact the course of RVF disease by determining whether differences in pathogenesis occurred in the presence or absence of mosquito saliva and salivary gland extract. C57BL/6NRJ male mice were infected with the ZH548 strain of RVFV via intraperitoneal or intradermal route, or via bites from RVFV-exposed mosquitoes. The virus titers in mosquitoes and mouse organs were determined by plaque assays. After intraperitoneal injection, RVFV infection primarily resulted in liver damage. In contrast, RVFV infection via intradermal injection caused both liver and neurological symptoms and this route best mimicked the natural infection by mosquitoes. Co-injections of RVFV with salivary gland extract or saliva via intradermal route increased the mortality rates of mice, as well as the virus titers measured in several organs and in the blood. Furthermore, the blood cell counts of infected mice were altered compared to those of uninfected mice. Different routes of infection determine the pattern in which the virus spreads and the organs it targets. Aedes saliva significantly increases the pathogenicity of RVFV.

A single center, open label study of intradermal administration of an inactivated purified chick embryo cell culture rabies virus vaccine in adults.

PubMed

Recuenco, Sergio; Warnock, Eli; Osinubi, Modupe O V; Rupprecht, Charles E

2017-08-03

In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only, although RVs are licensed for use by the intradermal (ID) route in many other countries. Recent limitations in supplies of RV in the USA reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential ID RV administration. A clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster vaccination. Enrollment included 130 adult volunteers. The arms with IM administration received vaccine according to the current ACIP recommendations: Pre-EP, three 1mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine Booster, one 1ml dose. The ID groups received the same schedule, but doses administered were in a volume of 0.1mL (0.25 I.U.). The rate of increase in rabies virus neutralizing antibody titers 14-21days after vaccination were similar in the ID and correspondent IM groups. The GMT values for ID vaccination were slightly lower than those for IM vaccination, for both naïve and booster groups, and these differences were statistically significant by t-test. Fourteen days after completing vaccination, all individuals developed RV neutralizing antibody titers over the minimum arbitrary value obtained with the rapid fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold until the end of the trial, 160days after completed vaccination. No serious adverse reactions were reported. Most frequent adverse reactions were erythema, induration and tenderness, localized at the site of injection. Multi use of 1mL rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and inmunogenic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age.

PubMed

Gorse, Geoffrey J; Falsey, Ann R; Johnson, Carol M; Morrison, Dennis; Fried, David L; Ervin, John E; Greenberg, David P; Ozol-Godfrey, Ayca; Landolfi, Victoria; Tsang, Peter H

2013-12-05

This clinical trial examined the safety and immunogenicity of annual revaccination with Fluzone(®) Intradermal (Sanofi Pasteur, Swiftwater, PA) vaccine compared to a standard intramuscular (IM) split-virion trivalent influenza vaccine (Fluzone(®), Sanofi Pasteur). This phase II, active-controlled, multi-centre, open-label trial was conducted in 2009 and 2010, and enrolled 1250 adults 18-64 years of age who were randomly selected from participants in a phase III influenza vaccine trial the previous year (NCT00772109). Subjects who had previously received the ID vaccine were randomized 2:1 to be revaccinated with the ID or IM vaccine and those who previously received the IM vaccine were randomized 1:1. Solicited reactions were recorded on the day of vaccination and continuing for the next 7 days, non-serious adverse events for 28 days, and serious adverse events for 6 months after vaccination. Hemagglutination inhibition antibody titres were assessed pre-vaccination and at day 28. Reactions were well-tolerated and resolved in the first 7 days, but erythema, induration, swelling, pruritus and ecchymosis were reported by more subjects receiving the ID vaccine than the IM vaccine. Compared to receipt of IM vaccine in the previous year, ID vaccine in the previous year led to statistically higher rates of erythema, swelling and induration after IM vaccine in the second year. Injection-site pain and systemic reactions did not differ between ID and IM vaccines. No treatment-related serious adverse events were reported. Geometric mean antibody titres, seroprotection rates, and seroconversion rates were non-inferior for the ID and IM vaccines for all three viral strains. The ID vaccine was as immunogenic as the IM vaccine, and raised no safety concerns. It can be used interchangeably with the IM vaccine for annual revaccination in adults 18-64 years of age in consecutive years without safety concerns. Copyright © 2013 Elsevier Ltd. All rights reserved.

The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients

PubMed Central

Gochi, A; Orita, K; Fuchimoto, S; Tanaka, N; Ogawa, N

2001-01-01

To investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg−1i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day−1) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5- and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5- and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micro- metastatic foci when compared to

Hydrodynamic gene delivery in human skin using a hollow microneedle device.

PubMed

Dul, M; Stefanidou, M; Porta, P; Serve, J; O'Mahony, C; Malissen, B; Henri, S; Levin, Y; Kochba, E; Wong, F S; Dayan, C; Coulman, S A; Birchall, J C

2017-11-10

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

The Netherlands strain of BTV serotype 8 in white-tailed deer

USDA-ARS?s Scientific Manuscript database

To determine the susceptibility of U.S. white-tailed deer to the European strain of BTV-8 (EU-BTV-8) isolated in The Netherlands, eight seronegative deer were injected subcutaneously in the neck and intradermally in the inner left leg. Two deer were sham inoculated to serve as uninfected controls an...

Incremental costs of introducing jet injection technology for delivery of routine childhood vaccinations: comparative analysis from Brazil, India, and South Africa.

PubMed

Griffiths, Ulla K; Santos, Andreia C; Nundy, Neeti; Jacoby, Erica; Matthias, Dipika

2011-01-29

Disposable-syringe jet injectors (DSJIs) have the potential to deliver vaccines safely and affordably to millions of children around the world. We estimated the incremental costs of transitioning from needles and syringes to delivering childhood vaccines with DSJIs in Brazil, India, and South Africa. Two scenarios were assessed: (1) DSJI delivery of all vaccines at current dose and depth; (2) a change to intradermal (ID) delivery with DSJIs for hepatitis B and yellow fever vaccines, while the other vaccines are delivered by DSJIs at current dose and depth. The main advantage of ID delivery is that only a small fraction of the standard dose may be needed to obtain an immune response similar to that of subcutaneous or intramuscular injection. Cost categories included were vaccines, injection equipment, waste management, and vaccine transport. Some delivery cost items, such as training and personnel were excluded as were treatment cost savings caused by a reduction in diseases transmitted due to unsafe injections. In the standard dose and depth scenario, the incremental costs of introducing DSJIs per fully vaccinated child amount to US$ 0.57 in Brazil, US$ 0.65 in India and US$ 1.24 in South Africa. In the ID scenario, there are cost savings of US$ 0.11 per child in Brazil, and added costs of US$ 0.45 and US$ 0.76 per child in India and South Africa, respectively. The most important incremental cost item is jet injector disposable syringes. The incremental costs should be evaluated against other vaccine delivery technologies that can deliver the same benefits to patients, health care workers, and the community. DSJIs deserve consideration by global and national decision-makers as a means to expand access to ID delivery and to enhance safety at marginal additional cost. Copyright © 2010 Elsevier Ltd. All rights reserved.

Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients

PubMed Central

Woodley, David T.; Cogan, Jon; Hou, Yingping; Lyu, Chao; Marinkovich, M. Peter; Keene, Douglas

2017-01-01

BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease caused by mutations in the gene encoding type VII collagen, the major component of anchoring fibrils (AF). We previously demonstrated that gentamicin produced functional type VII collagen in RDEB cells harboring nonsense mutations. Herein, we determined whether topical or intradermal gentamicin administration induces type VII collagen and AFs in RDEB patients. METHODS. A double-blind, placebo-controlled pilot trial assessed safety and efficacy of topical and intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2 open erosion sites for 2 weeks. The intradermal arm tested daily intradermal injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2 days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and AFs at the test sites and safety assessment. A secondary outcome assessed wound closure of topically treated erosions. RESULTS. Both topical and intradermal gentamicin administration induced type VII collagen and AFs at the dermal-epidermal junction of treatment sites. Newly created type VII collagen varied from 20% to 165% of that expressed in normal human skin and persisted for 3 months. Topical gentamicin corrected dermal-epidermal separation, improved wound closure, and reduced blister formation. There were no untoward side effects from gentamicin treatments. Type VII collagen induction did not generate anti–type VII collagen autoantibodies in patients’ blood or skin. CONCLUSION. Topical and intradermal gentamicin suppresses nonsense mutations and induces type VII collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily available treatment for RDEB patients with nonsense mutations. TRIAL REGISTRATION. ClinicalTrials.gov NCT02698735. FUNDING. Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa

Intradermal Skin Testing in Allergic Rhinitis and Asthma with Negative Skin Prick Tests.

PubMed

Erel, Fuat; Sarioglu, Nurhan; Kose, Mehmet; Kaymakci, Mustafa; Gokcen, Mucahide; Kepekci, Ahmet Hamdi; Arslan, Mehmet

2017-06-01

Taking medical history, physical examination, and performing some in vivo and in vitro tests are necessary for the diagnosis of allergy. Skin prick test (SPT) is considered as the standard method and first-line approach for the detection of allergic sensitization. Although mainly SPT is used for the detection of allergic sensitization, intradermal skin test (IDST) may be necessary, especially in patients with a negative SPT result. IDST is quite safe; however, is nowadays seldom used for detection of inhalant allergy and its value remains controversial. We aimed to investigate whether IDST is useful and necessary in diagnosis of respiratory allergies or not. This study involved 4223 patients with allergic rhinitis (AR) and/or bronchial asthma (BA). SPT results were positive in 2419 patients (57%) and negative in 1804 (43%). IDST was applied to 344 patients with marked allergic symptoms and with negative SPT results. Out of 344 patients, 152 (44%) showed allergic sensitization to IDST. The most commonly encountered allergic response was against the house dust mite (HDM) (32.6%). Allergic response against fungal spores was also relatively high (22%), while the pollen allergy rate (4.3%) was quite low. In BA patients with negative prick test, IDST made a significant contribution to the diagnosis of HDM allergy (p=0.003). To avoid missed diagnosis of AR and BA, particularly regarding  the HDM allergy, application of IDST may be beneficial; therefore, IDST should be considered as the next step after SPT for diagnosis of allergy prior to in vitro or provocation tests.

Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod-induced psoriasis-like inflammation.

PubMed

Pohin, Mathilde; Guesdon, William; Mekouo, Adela Andrine Tagne; Rabeony, Hanitriniaina; Paris, Isabelle; Atanassov, Hristo; Favot, Laure; Mcheik, Jiad; Bernard, François-Xavier; Richards, Carl D; Amiaud, Jérôme; Blanchard, Frédéric; Lecron, Jean-Claude; Morel, Franck; Jégou, Jean-François

2016-07-01

Oncostatin M (OSM) has been reported to be overexpressed in psoriasis skin lesions and to exert proinflammatory effects in vitro on human keratinocytes. Here, we report the proinflammatory role of OSM in vivo in a mouse model of skin inflammation induced by intradermal injection of murine OSM-encoding adenovirus (AdOSM) and compare with that induced by IL-6 injection. Here, we show that OSM potently regulates the expression of genes involved in skin inflammation and epidermal differentiation in murine primary keratinocytes. In vivo, intradermal injection of AdOSM in mouse ears provoked robust skin inflammation with epidermal thickening and keratinocyte proliferation, while minimal effect was observed after AdIL-6 injection. OSM overexpression in the skin increased the expression of the S100A8/9 antimicrobial peptides, CXCL3, CCL2, CCL5, CCL20, and Th1/Th2 cytokines, in correlation with neutrophil and macrophage infiltration. In contrast, OSM downregulated the expression of epidermal differentiation genes, such as cytokeratin-10 or filaggrin. Collectively, these results support the proinflammatory role of OSM when it is overexpressed in the skin. However, OSM expression was not required in the murine model of psoriasis induced by topical application of imiquimod, as demonstrated by the inflammatory phenotype of OSM-deficient mice or wild-type mice treated with anti-OSM antibodies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recombinant neutral endopeptidase attenuates substance P-induced plasma extravasation in the guinea pig skin.

PubMed

Rubinstein, I; Iwamoto, I; Ueki, I F; Borson, D B; Nadel, J A

1990-01-01

To determine whether exogenously administered neutral endopeptidase (NEP; enkephalinase, EC 3.4.24.11) inhibits the substance P-induced increase in vascular permeability in the skin, we examined the effects of recombinant human NEP on plasma extravasation induced by intradermal injection of substance P in guinea pig skin. Injection of substance P (2.5 X 10(-8) M) induced significant plasma extravasation in the skin (53 +/- 4 mm2 of Evans blue extravasation; mean +/- 1 SEM). In vitro incubation of substance P with recombinant human NEP prior to injection prevented the substance P-induced plasma extravasation in the skin in a dose-dependent fashion. Intradermal preinjection of recombinant human NEP partially inhibited plasma extravasation induced by subsequent injection of substance P (52 +/- 9% of the control without NEP). The H1 and H2 histamine antagonists pyrilamine and cimetidine, and a muscarinic antagonist, atropine, had no effects on substance P-induced responses. Two products of substance P degradation by NEP containing the carboxy-terminal portion, substance P7-11 and substance P8-11, were also without effect. These findings suggest that recombinant human NEP can attenuate substance P-induced increases in vascular permeability in guinea pig skin and, therefore, may be useful in treating dermatologic disorders in which abnormal responses to substance P or other neuropeptides cleaved by NEP may occur.

Nociceptive Afferent Activity Alters the SI RA Neuron Response to Mechanical Skin Stimulation

PubMed Central

Favorov, O.V.; Li, Y.; Lee, J.; Quibrera, P.M.; Tommerdahl, M.

2010-01-01

Procedures that reliably evoke cutaneous pain in humans (i.e., 5–7 s skin contact with a 47–51 °C probe, intradermal algogen injection) are shown to decrease the mean spike firing rate (MFR) and degree to which the rapidly adapting (RA) neurons in areas 3b/1 of squirrel monkey primary somatosensory cortex (SI) entrain to a 25-Hz stimulus to the receptive field center (RFcenter) when stimulus amplitude is “near-threshold” (i.e., 10–50 μm). In contrast, RA neuron MFR and entrainment are either unaffected or enhanced by 47–51 °C contact or intradermal algogen injection when the amplitude of 25-Hz stimulation is 100–200 μm (suprathreshold). The results are attributed to an “activity dependence” of γ-aminobutyric acid (GABA) action on the GABAA receptors of RA neurons. The nociceptive afferent drive triggered by skin contact with a 47–51 °C probe or intradermal algogen is proposed to activate nociresponsive neurons in area 3a which, via corticocortical connections, leads to the release of GABA in areas 3b/1. It is hypothesized that GABA is hyperpolarizing/inhibitory and suppresses stimulus-evoked RA neuron MFR and entrainment whenever RA neuron activity is low (as when the RFcenter stimulus is weak/near-threshold) but is depolarizing/excitatory and augments MFR and entrainment when RA neuron activity is high (when the stimulus is strong/suprathreshold). PMID:20308203

Intradermal testing after negative skin prick testing for patients with high suspicion of allergy.

PubMed

Larrabee, Yuna C; Reisacher, William

2015-06-01

Skin testing is a widely accepted method for identifying inhalant allergies. Intradermal (ID) testing is often performed after negative skin prick testing (SPT) when a practitioner has a high level of clinical suspicion for a particular allergen. A retrospective chart review study was performed over a 5-year period in patients with negative SPT for airborne allergens who also underwent ID testing based on a high level of suspicion for clinical allergy. Eighty-seven patients had negative SPT and went on to receive an average of 7 ID tests per patient. A total of 592 ID tests were performed after negative SPT. Of these, 20.8% (123/592) had a positive ID result with negative SPT. The allergens with the greatest percentage of positive ID results with negative SPTs were dog, cat, D. farinae, and D. pteronyssinus (33.3%, 34.3%, 39.4%, and 39.6%, respectively). The allergens least likely to test positive on ID testing after negative SPT were red maple, Cladosporium, and Alternaria (0%, 6.3%, and 6.5%, respectively). Approximately 20% of all negative results on SPT will have a positive ID test, more likely for indoor allergens. If a high suspicion for allergy exists in a patient with a negative SPT result, it may be useful to proceed with ID testing. However, the clinical significance of a positive ID test after negative SPT still needs to be elucidated. © 2015 ARS-AAOA, LLC.

Injection System for Multi-Well Injection Using a Single Pump

PubMed Central

Wovkulich, Karen; Stute, Martin; Protus, Thomas J.; Mailloux, Brian J.; Chillrud, Steven N.

2015-01-01

Many hydrological and geochemical studies rely on data resulting from injection of tracers and chemicals into groundwater wells. The even distribution of liquids to multiple injection points can be challenging or expensive, especially when using multiple pumps. An injection system was designed using one chemical metering pump to evenly distribute the desired influent simultaneously to 15 individual injection points through an injection manifold. The system was constructed with only one metal part contacting the fluid due to the low pH of the injection solutions. The injection manifold system was used during a three-month pilot scale injection experiment at the Vineland Chemical Company Superfund site. During the two injection phases of the experiment (Phase I = 0.27 L/min total flow, Phase II = 0.56 L/min total flow), flow measurements were made 20 times over three months; an even distribution of flow to each injection well was maintained (RSD <4%). This durable system is expandable to at least 16 injection points and should be adaptable to other injection experiments that require distribution of air-stable liquids to multiple injection points with a single pump. PMID:26140014

Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice.

PubMed

Impellizzeri, Daniela; Esposito, Emanuela; Di Paola, Rosanna; Ahmad, Akbar; Campolo, Michela; Peli, Angelo; Morittu, Valeria Maria; Britti, Domenico; Cuzzocrea, Salvatore

2013-01-01

N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35. Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.

Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice

PubMed Central

2013-01-01

Introduction N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). Methods CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35. Results Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. Conclusions We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA. PMID:24246048

Long-pulsed 1064-nm Nd: YAG laser ameliorates LL-37-induced rosacea-like skin lesions through promoting collagen remodeling in BALB/c mice.

PubMed

Kim, Miri; Kim, Jongsic; Jeong, Seo-Won; Jo, Hyunmu; Park, Hyun Jeong

2018-02-01

Long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser (LPND) effectively treats rosacea, although the underlying mechanism is unclear, to evaluate the histological effects and molecular mechanism of LPND on LL-37-induced rosacea-like skin lesions in mice. Intradermal injection of LL-37 was performed into the dorsal skin of BALB/c mice (n = 30) twice a day for 2 days. Fifteen mice were treated with LPND. After 48 h, the excised skin sample was stained for histology and type I collagen; transforming growth factor (TGF)-β, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase (TIMP)-1, tumor necrosis factor (TNF)-α, and interleukin (IL)-1α mRNA levels were determined by real-time RT-PCR. Intradermal injection of LL-37 induced rosacea-like clinical features. LPND treatment significantly reduced erythema and increased dermal collagen production. Levels of Type I collagen, TGF-β, and MMP-1 mRNA were significantly higher in LPND-treated mice than in untreated mice. LPND may improve rosacea by ameliorating dermal connective tissue disorganization and elastosis through MMP-mediated dermal collagen remodeling.

Biocompatibility of hyaluronic acid hydrogels prepared by porous hyaluronic acid microbeads

NASA Astrophysics Data System (ADS)

Kim, Jin-Tae; Lee, Deuk Yong; Kim, Tae-Hyung; Song, Yo-Seung; Cho, Nam-Ihn

2014-05-01

Hyaluronic acid hydrogels (HAHs) were synthesized by immersing HA microbeads crosslinked with divinyl sulfone in a phosphate buffered saline solution to evaluate the biocompatibility of the gels by means of cytotoxicity, genotoxicity ( in vitro chromosome aberration test, reverse mutation assay, and in vivo micronucleus test), skin sensitization, and intradermal reactivity. The HAHs induced no cytotoxicity or genotoxicity. In guinea pigs treated with grafts and prostheses, no animals died and there were no abnormal clinical signs. The sensitization scores were zero in all guinea pigs after 24 h and 48 h challenge, suggesting that the HAHs had no contact allergic sensitization in the guinea pig maximization test. No abnormal signs were found in New Zealand White rabbits during the 72 h observation period after the injection. There was no difference between the HAHs and negative control mean scores because skin reaction such as erythema or oedema was not observed after injection. Experimental results suggest that the HAHs would be suitable for soft tissue augmentation due to the absence of cytotoxicity, genotoxicity, skin sensitization, and intradermal reactivity.

Non-injection Drug Use and Injection Initiation Assistance among People Who Inject Drugs in Tijuana, Mexico.

PubMed

Ben Hamida, Amen; Rafful, Claudia; Jain, Sonia; Sun, Shelly; Gonzalez-Zuniga, Patricia; Rangel, Gudelia; Strathdee, Steffanie A; Werb, Dan

2018-02-01

Although most people who inject drugs (PWID) report receiving assistance during injection initiation events, little research has focused on risk factors among PWID for providing injection initiation assistance. We therefore sought to determine the influence of non-injection drug use among PWID on their risk to initiate others. We used generalized estimating equation (GEE) models on longitudinal data among a prospective cohort of PWID in Tijuana, Mexico (Proyecto El Cuete IV), while controlling for potential confounders. At baseline, 534 participants provided data on injection initiation assistance. Overall, 14% reported ever initiating others, with 4% reporting this behavior recently (i.e., in the past 6 months). In a multivariable GEE model, recent non-injection drug use was independently associated with providing injection initiation assistance (adjusted odds ratio [AOR] = 2.42, 95% confidence interval [CI] = 1.39-4.20). Further, in subanalyses examining specific drug types, recent non-injection use of cocaine (AOR = 9.31, 95% CI = 3.98-21.78), heroin (AOR = 4.00, 95% CI = 1.88-8.54), and methamphetamine (AOR = 2.03, 95% CI = 1.16-3.55) were all significantly associated with reporting providing injection initiation assistance. Our findings may have important implications for the development of interventional approaches to reduce injection initiation and related harms. Further research is needed to validate findings and inform future approaches to preventing entry into drug injecting.

Biogenicity and Syngeneity of Organic Matter in Ancient Sedimentary Rocks: Recent Advances in the Search for Evidence of Past Life

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 withmore » 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.« less

Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma.

PubMed

Roth, Udo; Razawi, Hanieh; Hommer, Julia; Engelmann, Katja; Schwientek, Tilo; Müller, Stefan; Baldus, Stephan E; Patsos, Georgios; Corfield, Anthony P; Paraskeva, Christos; Hanisch, Franz-Georg

2010-01-01

This is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE and is complemented by Western blot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms of over 2000 protein spots, 13 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in MALDI MS. Progression-associated proteins belong to the functional complexes of anaerobic glycolysis/gluconeogenesis, steroid biosynthesis, prostaglandin biosynthesis, the regulation and maintenance of the cytoskeleton, protein biosynthesis and degradation, the regulation of apoptosis or other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in colorectal carcinoma. Among upregulated proteins we identified 3-HMG-CoA synthase, protein phosphatase 1, prostaglandin E synthase 2, villin 1, annexin A1, triosephosphate isomerase, phosphoserine aminotransferase 1, fumarylacetoacetate hydrolase and pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78, cathepsin D, lamin A/C and quinolate phosphoribosyltransferase were downregulated.

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.

Shortening intradermal rabies post-exposure prophylaxis regimens to 1 week: Results from a phase III clinical trial in children, adolescents and adults.

PubMed

Kerdpanich, Phirangkul; Chanthavanich, Pornthep; De Los Reyes, Mari Rose; Lim, Jodor; Yu, Delia; Ama, Ma Cecilia; Mojares, Zenaida; Casula, Daniela; Arora, Ashwani Kumar; Pellegrini, Michele

2018-06-01

This phase III clinical trial compared the immunogenicity and safety of a purified chick-embryo cell rabies vaccine (PCECV) administered according to a shortened post-exposure prophylaxis (PEP) 4-site/1-week intradermal regimen, compared with the currently recommended 2-site/Thai Red Cross (TRC) regimen. This controlled, open-label, multi-center study (NCT02177032) enrolled healthy individuals ≥1 year of age, randomized into 4 groups to receive intradermal PCECV according to one of the 2 regimens, with or without human rabies immunoglobulin (HRIG) administration at first visit (in adults only). Rabies virus neutralizing antibody (RVNA) concentrations and percentages of participants with RVNA concentrations ≥0.5 IU/mL (considered as adequate concentrations following PEP) were assessed up to day (D) 365 post-first vaccination. Non-inferiority of the 4-site/1-week regimen to the 2-site/TRC regimen was demonstrated if at D49, the lower limit of the 95% confidence interval (CI) for the difference between groups in the percentage of participants with adequate RVNA concentrations was >-5%. Of the 443 participants receiving the 4-site/1-week regimen, 88 adults received HRIG; 442 participants received the 2-site/TRC regimen (88 with HRIG). All participants achieved adequate RVNA concentrations by D14. At D49, the difference in percentage of participants with adequate RVNA concentrations between the 4-site/1-week and the 2-site/TRC groups was -1 (95%CI: -2.4-0.0); thus, non-inferiority was concluded. RVNA geometric mean concentrations were 18 IU/mL in 4-site/1-week groups and 12 IU/mL in 2-site/TRC groups at D14, and subsequently declined in all groups. RVNA concentrations were consistently lower in adults with HRIG administration than in those without. The 2 regimens had similar safety profiles. Of the 15 serious adverse events reported in 4-site/1-week groups and 19 in 2-site/TRC groups, none were vaccination-related. The data suggest that the 4-site/1-week regimen

Diabetes Is Reversed in a Murine Model by Marginal Mass Syngeneic Islet Transplantation Using a Subcutaneous Cell Pouch Device.

PubMed

Pepper, Andrew R; Pawlick, Rena; Gala-Lopez, Boris; MacGillivary, Amanda; Mazzuca, Delfina M; White, David J G; Toleikis, Philip M; Shapiro, A M James

2015-11-01

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. 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. 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. 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.

Granisetron Injection

MedlinePlus

... and vomiting that may occur after surgery. Granisetron extended-release (long-acting) injection is used with other ... be injected intravenously (into a vein) and granisetron extended-release injection comes as a liquid to be ...

Deltoid Injections of Risperidone Long-acting Injectable in Patients with Schizophrenia

PubMed Central

Quiroz, Jorge A.; Rusch, Sarah; Thyssen, An; Kushner, Stuart

2011-01-01

Background Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Methods Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. Results In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Conclusion Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites. PMID:21779538

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

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. Copyright © 2014 Elsevier B.V. All rights reserved.

Nusinersen Injection

MedlinePlus

Nusinersen injection comes as a solution (liquid) to inject intrathecally (into the fluid-filled space of the spinal canal). Nusinersen injection is given by a doctor in a medical office or clinic. It is usually given as ...

Acute immunosuppression and syngeneic bone marrow transplantation in ocular autoimmunity abort disease, but do not result in induction of long-term protection.

PubMed

Savion, S; Silver, P B; Chan, C C; Caspi, R R

1998-09-01

Acute immunosuppression induced by total body irradiation (TBI) or cyclophosphamide (Cy) treatment, followed by syngeneic bone marrow transplantation (SBMT), was reported to be effective in inducing long-term tolerance in some autoimmune disease models. We examined the efficacy of this approach in the mouse model of experimental autoimmune uveoretinitis (EAU). Development of EAU induced by the interphotoreceptor retinoid binding protein (IRBP) was abolished almost completely by either TBI or Cy treatment, followed by SBMT, instituted one week after priming. In parallel, IRBP-specific delayed-type hypersensitivity (DTH) responses and lymph node cell proliferation were strongly suppressed or abolished. However, when these IRBP-immunized, lymphoablated and BM reconstituted mice were rechallenged with the immunizing antigen seven weeks after the primary immunization, they were not protected from developing disease, despite the fact that DTH and lymph node cell proliferation to the antigen were suppressed relative to controls. TBI treatment appeared somewhat more effective than Cy treatment as judged by its more profound effect on immunological responses. These results demonstrate the ability of acute immunosuppression followed by reconstitution of the immune system to inhibit the development of EAU, although long-term protection from disease was not achieved.

Microneedles: quick and easy delivery methods of vaccines

PubMed Central

2017-01-01

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route. PMID:28775980

TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds.

PubMed

Qi, Yu; Jiang, Dongsheng; Sindrilaru, Anca; Stegemann, Agatha; Schatz, Susanne; Treiber, Nicolai; Rojewski, Markus; Schrezenmeier, Hubert; Vander Beken, Seppe; Wlaschek, Meinhard; Böhm, Markus; Seitz, Andreas; Scholz, Natalie; Dürselen, Lutz; Brinckmann, Jürgen; Ignatius, Anita; Scharffetter-Kochanek, Karin

2014-02-01

Proper activation of macrophages (Mφ) in the inflammatory phase of acute wound healing is essential for physiological tissue repair. However, there is a strong indication that robust Mφ inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studies, we here addressed the question of whether mesenchymal stem cells (MSCs)-due to their anti-inflammatory properties-would control Mφ activation and tissue fibrosis in a murine model of full-thickness skin wounds. We have shown that the tumor necrosis factor-α (TNF-α)-stimulated protein 6 (TSG-6) released from MSCs in co-culture with activated Mφ or following injection into wound margins suppressed the release of TNF-α from activated Mφ and concomitantly induced a switch from a high to an anti-fibrotic low transforming growth factor-β1 (TGF-β1)/TGF-β3 ratio. This study provides insight into what we believe to be a previously undescribed multifaceted role of MSC-released TSG-6 in wound healing. MSC-released TSG-6 was identified to improve wound healing by limiting Mφ activation, inflammation, and fibrosis. TSG-6 and MSC-based therapies may thus qualify as promising strategies to enhance tissue repair and to prevent excessive tissue fibrosis.

Measuring tissue back-pressure--in vivo injection forces during subcutaneous injection.

PubMed

Allmendinger, Andrea; Mueller, Robert; Schwarb, Edward; Chipperfield, Mark; Huwyler, Joerg; Mahler, Hanns-Christian; Fischer, Stefan

2015-07-01

Limited information is available on injection forces of parenterals representing the in vivo situation. Scope of the present study was to investigate the contribution of the subcutaneous (sc) tissue layer to injection forces during in vivo injection. Göttingen minipigs received injections of isotonic dextran solutions (1-100 mPas) into the plica inguinalis using different injection rates and volumes (0.025-0.2 mL/s and 2.5 vs. 4.5 mL). The contribution of the sc back-pressure to injection forces was found to increase linearly with viscosity and injection rate ranging from 0.6 ± 0.5 N to 1.0 ± 0.4 N (1 mPas), 0.7 ± 0.2 N to 2.4 ± 1.9 N (10 mPas), and 1.8 ± 0.6 N to 4.7 ± 3.3 N (20 mPas) for injection rates of 0.025 to 0.2 mL/s, respectively. Variability increased with viscosity and injection rate. Values are average values from 10 randomized injections. A maximum of 12.9 N was reached for 20 mPas at 0.2 mL/s; 6.9 ± 0.3 N was determined for 100 mPas at 0.025 mL/s. No difference was found between injection volumes of 2.5 and 4.5 mL. The contribution of the tissue was differentiated from the contribution of the injection device and a local temperature effect. This effect was leading to warming of the (equilibrated) sample in the needle, therefore smaller injection forces than expected compensating tissue resistance to some parts. When estimating injection forces representative for the in vivo situation, the contribution of the tissue has to be considered as well as local warming of the sample in the needle during injection.

Continuous in vivo infusion of interferon-gamma (IFN-gamma) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice.

PubMed

Si, Yue; Ciccone, Samantha; Yang, Feng-Chun; Yuan, Jin; Zeng, Daisy; Chen, Shi; van de Vrugt, Henri J; Critser, John; Arwert, Fre; Haneline, Laura S; Clapp, D Wade

2006-12-15

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc-/- cells to interferon-gamma (IFN-gamma), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc-/- mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca-/- and Fancg-/- mice are hypersensitive to IFN-gamma and that in vivo infusion of IFN-gamma at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-gamma conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients.

Optimization of a gene electrotransfer procedure for efficient intradermal immunization with an hTERT-based DNA vaccine in mice

PubMed Central

Calvet, Christophe Y; Thalmensi, Jessie; Liard, Christelle; Pliquet, Elodie; Bestetti, Thomas; Huet, Thierry; Langlade-Demoyen, Pierre; Mir, Lluis M

2014-01-01

DNA vaccination consists in administering an antigen-encoding plasmid in order to trigger a specific immune response. This specific vaccine strategy is of particular interest to fight against various infectious diseases and cancer. Gene electrotransfer is the most efficient and safest non-viral gene transfer procedure and specific electrical parameters have been developed for several target tissues. Here, a gene electrotransfer protocol into the skin has been optimized in mice for efficient intradermal immunization against the well-known telomerase tumor antigen. First, the luciferase reporter gene was used to evaluate gene electrotransfer efficiency into the skin as a function of the electrical parameters and electrodes, either non-invasive or invasive. In a second time, these parameters were tested for their potency to generate specific cellular CD8 immune responses against telomerase epitopes. These CD8 T-cells were fully functional as they secreted IFNγ and were endowed with specific cytotoxic activity towards target cells. This simple and optimized procedure for efficient gene electrotransfer into the skin using the telomerase antigen is to be used in cancer patients for the phase 1 clinical evaluation of a therapeutic cancer DNA vaccine called INVAC-1. PMID:26015983

Immune Responses Induced by Gene Gun or Intramuscular Injection of DNA Vaccines That Express Immunogenic Regions of the Serine Repeat Antigen from Plasmodium falciparum

PubMed Central

Belperron, Alexia A.; Feltquate, David; Fox, Barbara A.; Horii, Toshihiro; Bzik, David J.

1999-01-01

The liver- and blood-stage-expressed serine repeat antigen (SERA) of Plasmodium falciparum is a candidate protein for a human malaria vaccine. We compared the immune responses induced in mice immunized with SERA-expressing plasmid DNA vaccines delivered by intramuscular (i.m.) injection or delivered intradermally by Gene Gun immunization. Mice were immunized with a pcdna3 plasmid encoding the entire 47-kDa domain of SERA (amino acids 17 to 382) or the N-terminal domain (amino acids 17 to 110) of SERA. Minimal antibody responses were detected following DNA vaccination with the N-terminal domain of SERA, suggesting that the N-terminal domain alone is not highly immunogenic by this route of vaccine delivery. Immunization of mice by Gene Gun delivery of the 47-kDa domain of SERA elicited a significantly higher serum antibody titer to the antigen than immunization of mice by i.m. injection with the same plasmid did. The predominant isotype subclass of the antibodies elicited to the SERA protein following i.m. and Gene Gun immunizations with SERA plasmid DNA was immunoglobulin G1. Coimmunization of mice with SERA plasmid DNA and a plasmid expressing the hepatitis B surface antigen (pCMV-s) by the i.m. route resulted in higher anti-SERA titers than those generated in mice immunized with the SERA DNA plasmid alone. Vaccination with DNA may provide a viable alternative or may be used in conjunction with protein-based subunit vaccines to maximize the efficacy of a human malaria vaccine that includes immunogenic regions of the SERA protein. PMID:10496891

Compressed air injection technique to standardize block injection pressures.

PubMed

Tsui, Ban C H; Li, Lisa X Y; Pillay, Jennifer J

2006-11-01

Presently, no standardized technique exists to monitor injection pressures during peripheral nerve blocks. Our objective was to determine if a compressed air injection technique, using an in vitro model based on Boyle's law and typical regional anesthesia equipment, could consistently maintain injection pressures below a 1293 mmHg level associated with clinically significant nerve injury. Injection pressures for 20 and 30 mL syringes with various needle sizes (18G, 20G, 21G, 22G, and 24G) were measured in a closed system. A set volume of air was aspirated into a saline-filled syringe and then compressed and maintained at various percentages while pressure was measured. The needle was inserted into the injection port of a pressure sensor, which had attached extension tubing with an injection plug clamped "off". Using linear regression with all data points, the pressure value and 99% confidence interval (CI) at 50% air compression was estimated. The linearity of Boyle's law was demonstrated with a high correlation, r = 0.99, and a slope of 0.984 (99% CI: 0.967-1.001). The net pressure generated at 50% compression was estimated as 744.8 mmHg, with the 99% CI between 729.6 and 760.0 mmHg. The various syringe/needle combinations had similar results. By creating and maintaining syringe air compression at 50% or less, injection pressures will be substantially below the 1293 mmHg threshold considered to be an associated risk factor for clinically significant nerve injury. This technique may allow simple, real-time and objective monitoring during local anesthetic injections while inherently reducing injection speed.

Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid

PubMed Central

Chen, Ruoyan; Ning, Gang; Zhao, Ming-Lang; Fleming, Matthew G.; Diaz, Luis A.; Werb, Zena; Liu, Zhi

2001-01-01

Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with an IgG autoimmune response to the hemidesmosomal protein BP180. Passive transfer of antibodies to the murine BP180 (mBP180) ectodomain triggers a blistering skin disease in mice that depends on complement activation and neutrophil infiltration and closely mimics human BP. In the present study, we show that mast cells (MCs) play a crucial role in experimental BP. Wild-type mice injected intradermally with pathogenic anti-mBP180 IgG exhibited extensive MC degranulation in skin, which preceded neutrophil infiltration and subsequent subepidermal blistering. In contrast, mice genetically deficient in MCs or MC-sufficient mice pretreated with an inhibitor of MC degranulation failed to develop BP. Further, MC-deficient mice reconstituted in skin with MCs became susceptible to experimental BP. Despite the activation of complement to yield C3a and C5a, in the absence of MCs, accumulation of neutrophils at the injection site was blunted. The lack of response due to MC deficiency was overcome by intradermal administration of a neutrophil chemoattractant, IL-8, or by reconstitution of the injection sites with neutrophils. These findings provide the first direct evidence to our knowledge that MCs play an essential role in neutrophil recruitment during subepidermal blister formation in experimental BP. PMID:11602622

"Injection first": a unique group of injection drug users in Tijuana, Mexico.

PubMed

Morris, Meghan D; Brouwer, Kimberly C; Lozada, Remedios M; Gallardo, Manuel; Vera, Alicia; Strathdee, Steffanie A

2012-01-01

Using baseline data from a study of injection drug users (IDUs) in Tijuana, Mexico (N = 1,052), we identified social and behavioral factors associated with injecting at the same age or earlier than other administration routes of illicit drug use (eg, "injection first") and examined whether this IDU subgroup had riskier drug using and sexual behaviors than other IDUs. Twelve-percent "injected first." Characteristics independently associated with a higher odds of "injection first" included being younger at first injection, injecting heroin as their first drug, being alone at the first injection episode, and having a sexual debut at the same age or earlier as when they initiated drug use; family members' illicit drug use was associated with lower odds of injecting first. When adjusting for age at first injection and number of years injecting, "injection first" IDUs had lower odds of ever overdosing, and ever trading sex. On the other hand, they were less likely to have ever been enrolled in drug treatment, and more commonly obtained their syringes from potentially unsafe sources. In conclusion, a sizable proportion of IDUs in Tijuana injected as their first drug using experience, although evidence that this was a riskier subgroup of IDUs was inconclusive.  Copyright © American Academy of Addiction Psychiatry.

Prevalence and characteristics of femoral injection among Seattle-area injection drug users.

PubMed

Coffin, Phillip O; Coffin, Lara S; Murphy, Shilo; Jenkins, Lindsay M; Golden, Matthew R

2012-04-01

Injection drug use (IDU) into central veins, most common among long-term IDUs with no other options, can lead to severe infectious, vascular, and traumatic medical consequences. To follow-up on anecdotal reports of femoral vein injection and related medical problems in Seattle, we analyzed data from the annual survey of a community-based syringe exchange program. A total of 276 (81%) of 343 program attendees completed the survey in August 2010. Among 248 IDUs, 66% were male, 78% white, and 86% primarily injected opiates. One hundred respondents (40%) had injected into the femoral vein, 55% of whom were actively doing so, and 58% of whom reported medical complications that they attributed to the practice. Most (66%) used the femoral vein due to difficulty accessing other veins, although 61% reported other veins they could access and 67% reporting using other sites since initiating femoral injection. While injecting into muscle was more frequent among older IDUs with longer injection careers, the prevalence of femoral injection was highest among respondents in their late twenties with 2.5-6 years of injecting drugs. Multivariate analysis demonstrated an increased risk of initiating femoral injection each calendar year after 2007. Injecting into the femoral vein was also associated with white versus other race (odds ratio [OR] 2.7, 95% CI 1.3-5.4) and injection of primarily opiates versus other drugs (OR 6.3, 95% CI 1.2-32.9) and not associated with age, length of IDU career, or a history of injecting into muscle. These findings suggest a secular trend of increasing femoral injection among Seattle-area IDUs with a high rate of related medical problems. Interventions, such as education regarding the hazards of central venous injection and guidance on safe injection into peripheral veins, are needed to minimize the health consequences of femoral injection.

Tolerance and immunity in mice infected with herpes simplex virus: studies on the mechanism of tolerance to delayed-type hypersensitivity.

PubMed

Nash, A A; Phelan, J; Gell, P G; Wildy, P

1981-06-01

Tolerance to delayed-type hypersensitivity is produced in mice following an intravenous injection of herpes simplex virus. This form of tolerance is produced early on, following simultaneous injections of virus subcutaneously and intravenously, and is long lasting (greater than 100 days). The early tolerance mechanism is resistant to high doses of cyclophosphamide and is not transferable by serum or spleen cells taken after 7 days. However, spleen cells taken at 14 days onwards inhibit the induction of delayed hypersensitivity when transferred to normal syngeneic recipients. These cells are T lymphocytes and are specific for the herpes type used in the induction.

Tolerance and immunity in mice infected with herpes simplex virus: studies on the mechanism of tolerance to delayed-type hypersensitivity.

PubMed Central

Nash, A A; Phelan, J; Gell, P G; Wildy, P

1981-01-01

Tolerance to delayed-type hypersensitivity is produced in mice following an intravenous injection of herpes simplex virus. This form of tolerance is produced early on, following simultaneous injections of virus subcutaneously and intravenously, and is long lasting (greater than 100 days). The early tolerance mechanism is resistant to high doses of cyclophosphamide and is not transferable by serum or spleen cells taken after 7 days. However, spleen cells taken at 14 days onwards inhibit the induction of delayed hypersensitivity when transferred to normal syngeneic recipients. These cells are T lymphocytes and are specific for the herpes type used in the induction. PMID:6265348

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

Cosmeceutical effect of ethyl acetate fraction of Kombucha tea by intradermal administration in the skin of aged mice.

PubMed

Pakravan, Nafiseh; Mahmoudi, Elaheh; Hashemi, Seyed-Ali; Kamali, Jamal; Hajiaghayi, Reza; Rahimzadeh, Mitra; Mahmoodi, Vajiheh

2017-11-19

Natural ingredients have been always an interesting approach to prolong youthful appearance of skin. One of the natural compounds is Kombucha tea (KT), which has been mainly used as an energy drink in Asian countries for a long time. Previous reports indicated that it has pharmaceutical and favorable wound repairing effects. The beneficial properties of KT are thought to be mainly due to the presence of fermentation products such as flavonoids and other polyphenols with inhibition of hydrolytic and oxidative enzymes and anti-inflammatory effects. These properties prompted us to study the anti-aging potential of KT and investigate its effective fraction in aged mice, METHODS: Kombucha tea was fractionated into chloroform, butanol, and ethyl acetate, and flavonoid content was determined. Young and old mice were used as control. KT ethyl acetate fraction (KEAf), which had the highest flavonoid content, was intradermally administered to old mice. Administration of KEAf significantly increased the collagen content, NAD + /NADH level, and concomitantly improved skin connective tissue abnormalities in the aged skin. No sensitivity or irritation was observed. This finding suggested that KEAf can be a suitable candidate as a cosmetic product to improve aging-related skin abnormalities and regeneration of aged skin. © 2017 Wiley Periodicals, Inc.

Further Observations on the Effect of C. parvum and Anti-Tumour Globulin on Syngeneically Transplanted Mouse Tumours

PubMed Central

Woodruff, M. F. A.; Inchley, M. P.; Dunbar, Noreen

1972-01-01

The inhibitory effect of an i.v. or i.p. injection of C. parvum on intrastrain transplants of a mammary carcinoma in A/HeJ mice has been confirmed, and it has been shown further that C. parvum inhibits the growth of transplants of sarcomata induced with methylcholanthrene both in this strain (members of which lack the fifth component of complement) and in CBA mice (which are not complement deficient). In experiments with the mammary carcinoma, 2 injections of C. parvum on days + 3 and + 9 were more effective than a single injection on day + 3; injections on days + 3 and + 6, or + 3 and + 12, appeared to be marginally less effective than on days + 3 and + 9, but the difference was not statistically significant. Development of the CBA sarcoma was inhibited to about the same extent if, instead of treating the mouse with C. parvum, the tumour cells were pre-incubated with anti-tumour globulin (ATG) in the absence of complement prior to inoculation, and the effect of combining these procedures was much greater than that of either alone. Pre-incubation with ATG had a similar but less marked effect on the development of the mammary carcinoma but had no effect on the A/HeJ sarcoma. Injection (i.v.) of ATG did not inhibit the growth of any of the tumours in these experiments and possible reasons for this are discussed. PMID:5038327

Platelet-rich plasma-containing fragmin-protamine micro-nanoparticles promote epithelialization and angiogenesis in split-thickness skin graft donor sites.

PubMed

Takabayashi, Yuki; Ishihara, Masayuki; Sumi, Yuki; Takikawa, Makoto; Nakamura, Shingo; Kiyosawa, Tomoharu

2015-01-01

Platelet-rich plasma (PRP) contains multiple growth factors, and fragmin-protamine micro-nanoparticles (F-P M-NPs) significantly enhance and stabilize growth factors. The purpose of this study was to evaluate the effects of PRP-containing F-P M-NPs (PRP&F-P M-NPs) on wound repair in split-thickness skin graft (STSG-) donor sites (DS). A total of 56 inbred male rats were anesthetized and split-thickness skin graft donor site (STSG-DS) were created with a Padgett dermatome. PRP&F-P M-NPs, F-P M-NPs, PRP, and saline (control) were then intradermally injected evenly into the STSG-DSs. On 3, 4, 5, 7, and 10 d after creation of STSG-DS, skin sample sections were stained with hematoxylin and eosin to evaluate reepithelialization and angiogenesis. Treatment of STSG-DS with PRP&F-P M-NPs effectively promoted epithelialization and new vessel formation compared with those treated with PRP, F-P M-NPs, and control (saline). The intradermal injection of PRP&F-P M-NPs promotes epithelialization and angiogenesis in STSG-DS wounds. Copyright © 2015 Elsevier Inc. All rights reserved.

Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.

PubMed

Jakobsen, Maria; Askou, Anne Louise; Stenderup, Karin; Rosada, Cecilia; Dagnæs-Hansen, Frederik; Jensen, Thomas G; Corydon, Thomas J; Mikkelsen, Jacob Giehm; Aagaard, Lars

2015-08-01

Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, we compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotransplanted mouse model. Vector constructs encoding firefly luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and separately administered by intradermal injection in human skin transplants. For all serotypes, live bioimaging demonstrated low levels of transgene expression in the human skin graft, and firefly luciferase expression was observed primarily in neighboring tissue outside of the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin graft only. The study demonstrates the limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo.

Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin

PubMed Central

Jakobsen, Maria; Askou, Anne Louise; Stenderup, Karin; Rosada, Cecilia; Dagnæs-Hansen, Frederik; Jensen, Thomas G.; Corydon, Thomas J.; Mikkelsen, Jacob Giehm; Aagaard, Lars

2015-01-01

Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, we compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotransplanted mouse model. Vector constructs encoding firefly luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and separately administered by intradermal injection in human skin transplants. For all serotypes, live bioimaging demonstrated low levels of transgene expression in the human skin graft, and firefly luciferase expression was observed primarily in neighboring tissue outside of the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin graft only. The study demonstrates the limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo. PMID:26204415

Peripheral gabapentin regulates mosquito allergy-induced itch in mice.

PubMed

Akiyama, Tasuku; Andoh, Tsugunobu; Ohtsuka, Eiji; Nojima, Hiroshi; Ouchi, Hidekazu; Takahata, Hiroki; Kuraishi, Yasushi

2018-05-26

The antipruritic activity of gabapentin, an anticonvulsant, was studied in a mouse model of allergic itch. In mice sensitized by an extract of the salivary glands of the mosquito (ESGM), an intradermal injection of ESGM elicited scratching and increased peripheral nerve firing. Oral or intradermal administration of gabapentin at the ESGM injection site inhibited ESGM-induced scratching and peripheral nerve firing. However, gabapentin did not affect histamine-induced scratching. The distributions of immunoreactivity to the voltage-dependent calcium channel α 2 δ-1 subunit, a site of gabapentin action, and the histamine H 1 receptor differed in the mouse dorsal root ganglia. The α 2 δ-1 subunit was mainly found in neurons that were 15-20 µm in diameter, whereas the H 1 receptor was mainly in 20-30 µm neurons. In addition, α 2 δ-1 subunit immunoreactivity co-localized with that of transient receptor potential vanilloid 1 (TRPV1). These results suggest that gabapentin regulates allergic itch by acting on the calcium channel α 2 δ-1 subunit in peripheral TRPV1-positive neurons. Copyright © 2018 Elsevier B.V. All rights reserved.

Characteristics of MIC-1 antlerogenic stem cells and their effect on hair growth in rabbits.

PubMed

Cegielski, Marek; Izykowska, Ilona; Chmielewska, Magdalena; Dziewiszek, Wojciech; Bochnia, Marek; Calkosinski, Ireneusz; Dziegiel, Piotr

2013-01-01

We characterized growth factors produced by MIC-1 antlerogenic stem cells and attempted to apply those cells to stimulate hair growth in rabbits. We evaluated the gene and protein expression of growth factors by immunocytochemical and molecular biology techniques in MIC-1 cells. An animal model was used to assess the effects of xenogenous stem cells on hair growth. In the experimental group, rabbits were intradermally injected with MIC-1 stem cells, whereas the control group rabbits were given vehicle-only. After 1, 2 and 4 weeks, skin specimen were collected for histological and immunohistochemical tests. MIC-1 antlerogenic stem cells express growth factors, as confirmed at the mRNA and protein levels. Histological and immunohistochemical analysis demonstrated an increase in the number of hair follicles, as well as the amount of secondary hair in the follicles, without an immune response in animals injected intradermally with MIC-1 cells, compared to animals receiving vehicle-alone. MIC-1 cells accelerated hair growth in rabbits due to the activation of cells responsible for the regulation of the hair growth cycle through growth factors. Additionally, the xenogenous cell implant did not induce immune response.

Modified short-term guinea pig sensitization tests for detecting contact allergens as an alternative to the conventional test.

PubMed

Yanagi, M; Hoya, M; Mori, M; Katsumura, Y

2001-03-01

The conventional adjuvant and patch test (APT) method of guinea pig sensitization testing was modified in 2 ways, s-APT and s-APT(2), in order to shorten the test period. These short-term test methods consist of 72-h closed application of test material with intradermal injection of emulsified Freund's complete adjuvant (E-FCA) for 1st induction, 48-h closed application of test material with (s-APT) or without (s-APT(2)) intradermal injection of E-FCA on the 7th day for 2nd induction, and open application on the 14th day for challenge. They were compared with conventional APT by using 8 allergenic chemicals (formaldehyde, nickel sulfate, cobalt sulfate, ethyl-p-aminobenzoate (benzocaine), isoeugenol, 2-mercaptobenzothiazole, 2,4-dinitrochlorobenzene (DNCB) and 1-phenylazo-2-naphthol (Sudan I)). The short-term methods gave similar results to those of conventional APT in terms of mean response, sensitization rate and sensitization potency (challenge concentration that induces a mean response equal to 1.0). Thus, our short-term methods, which are capable of evaluating skin sensitization within 17 days, are sufficiently sensitive to detect potentially hazardous contact allergens.

Immune response of mallard ducks treated with immunosuppressive agents: antibody response to erythrocytes and in vivo response to phytohemagglutinin-P.

USGS Publications Warehouse

Schrank, C.S.; Cook, M.E.; Hansen, W.R.

1990-01-01

The ability of two in vivo tests to assay immune competence of mallard ducks (Anas platyrhynchos) treated with various immunomodulatory agents was examined. Skin responses to phytohemagglutinin-P (PHA-P) injected intradermally and serum antibody levels produced in response to sheep red blood cells (SRBC) were measured. As measured by the skin response to PHA-P, ducks injected intramuscularly with cyclophosphamide or cyclosporine did not respond differently from control-injected ducks. Dexamethasone injected intramuscularly significantly suppressed the skin response to PHA-P. As measured by antibody levels in response to SRBC, ducks injected intramuscularly with cyclophosphamide responded with antibody titers similar to controls. Cyclosporine injected intramuscularly reduced the level of immunoglobulin (Ig) G significantly in one of two experiments. Dexamethasone injected intramuscularly reduced peak total and IgG titers. These experiments provide information on the viability of these two in vivo tests to reflect immune competence of mallard ducks.

Dendritic Cell-Based Vaccines that Utilize Myeloid Rather than Plasmacytoid Cells Offer a Superior Survival Advantage in Malignant Glioma.

PubMed

Dey, Mahua; Chang, Alan L; Miska, Jason; Wainwright, Derek A; Ahmed, Atique U; Balyasnikova, Irina V; Pytel, Peter; Han, Yu; Tobias, Alex; Zhang, Lingjiao; Qiao, Jian; Lesniak, Maciej S

2015-07-01

Dendritic cells (DCs) are professional APCs that are traditionally divided into two distinct subsets, myeloid DC (mDCs) and plasmacytoid DC (pDCs). pDCs are known for their ability to secrete large amounts of IFN-α. Apart from IFN-α production, pDCs can also process Ag and induce T cell immunity or tolerance. In several solid tumors, pDCs have been shown to play a critical role in promoting tumor immunosuppression. We investigated the role of pDCs in the process of glioma progression in the syngeneic murine model of glioma. We show that glioma-infiltrating pDCs are the major APC in glioma and are deficient in IFN-α secretion (p < 0.05). pDC depletion leads to increased survival of the mice bearing intracranial tumor by decreasing the number of regulatory T cells (Tregs) and by decreasing the suppressive capabilities of Tregs. We subsequently compared the ability of mDCs and pDCs to generate effective antiglioma immunity in a GL261-OVA mouse model of glioma. Our data suggest that mature pDCs and mDCs isolated from naive mice can be effectively activated and loaded with SIINFEKL Ag in vitro. Upon intradermal injection in the hindleg, a fraction of both types of DCs migrate to the brain and lymph nodes. Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4(+)T-bet(+) T cells and CD8(+)SIINFEKEL(+) T cells. This robust antitumor T cell response results in tumor eradication and long-term survival in 60% of the animals (p < 0.001). Copyright © 2015 by The American Association of Immunologists, Inc.

Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors

NASA Astrophysics Data System (ADS)

Giustini, Andrew J.; Petryk, Alicia A.; Hoopes, Paul J.

2011-03-01

Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 +/- 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.

Rejuvenation of aged pig facial skin by transplanting allogeneic granulocyte colony-stimulating factor-induced peripheral blood stem cells from a young pig.

PubMed

Harn, Horng-Jyh; Huang, Mao-Hsuan; Huang, Chi-Ting; Lin, Po-Cheng; Yen, Ssu-Yin; Chou, Yi-Wen; Ho, Tsung-Jung; Chu, Hen-Yi; Chiou, Tzyy-Wen; Lin, Shinn-Zong

2013-01-01

Following a stroke, the administration of stem cells that have been treated with granulocyte colony-stimulating factor (GCSF) can ameliorate functional deficits in both rats and humans. It is not known, however, whether the application of GCSF-mobilized peripheral blood stem cells (PBSCs) to human skin can function as an antiaging treatment. We used a Lanyu pig (Sus scrofa) model, since compared with rodents, the structure of a pig's skin is very similar to human skin, to provide preliminary data on whether these cells can exert antiaging effects over a short time frame. GCSF-mobilized PBSCs from a young male Lanyu pig (5 months) were injected intradermally into the cheek skin of aged female Lanyu pigs, and tissues before and after the cell injections were compared to determine whether this treatment caused skin rejuvenation. Increased levels of collagen, elastin, hyaluronic acid, and the hyaluronic acid receptor CD44 were observed in both dermal and subcutaneous layers following the injection of PBSCs. In addition, the treated skin tissue was tighter and more elastic than adjacent control regions of aged skin tissue. In the epidermal layer, PBSC injection altered the levels of both involucrin and integrin, indicating an increased rate of epidermal cell renewal as evidenced by reductions in both cornified cells and cells of the spinous layers and increases in the number of dividing cells within the basal layer. We found that the exogenous PBSCs, visualized using fluorescence in situ hybridization, were located primarily in hair follicles and adjacent tissues. In summary, PBSC injection restored young skin properties in the skin of aged (90 months) pigs. On the basis of our preliminary data, we conclude that intradermal injection of GCSF-mobilized PBSCs from a young pig can rejuvenate the skin in aged pigs.

Influence of the Tumor Microenvironment on Genomic Changes Conferring Chemoresistance in Breast Cancer

DTIC Science & Technology

2013-04-01

tumor microenvironment on clonal selection using intravital microscopy Jae-Hyun Park 1 , Miriam R. Fein 1 , Mikala Egeblad 1 1 Cold Spring Harbor...used surgically implanted mammary imaging windows in immunocompetent mice and injected “brainbow” expressing, syngeneic 4T1 breast carcinoma cells...under the windows. This allowed us to acquire multiple time- lapse imaging series by spinning disk confocal microscopy of the same tumor, done about 3

US Army Medical Research and Development Technical Report

DTIC Science & Technology

1975-07-01

very similar in extent and appearance to naturally occurring human infections and the armadillo appears to be the best experimental model for...guinea pig skin produced by intradermal injection of toxin fractions resemble the early changes in naturally occurring human infections. In both there... naturally occurring human infections. In both there is extensive necrosis, undermining of the margins of the lesions and a spreading contiguous necrosis

Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Runge, V.M.; Rand, T.H.; Clanton, J.A.

1983-05-01

Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study ofmore » parasitic and allergic disease.« less

Adoptively transferred dendritic cells restore primary cell-mediated inflammatory competence to acutely malnourished weanling mice.

PubMed

Hillyer, Lyn; Whitley, Charlene; Olver, Amy; Webster, Michelle; Steevels, Tessa; Woodward, Bill

2008-02-01

Immune depression associated with prepubescent malnutrition underlies a staggering burden of infection-related morbidity. This investigation centered on dendritic cells as potentially decisive in this phenomenon. C57BL/6J mice, initially 19 days old, had free access for 14 days to a complete diet or to a low-protein formulation that induced wasting deficits of protein and energy. Mice were sensitized by i.p. injection of sheep red blood cells on day 9, at which time one-half of the animals in each dietary group received a simultaneous injection of 10(6) syngeneic dendritic cells (JAWS II). All mice were challenged with the immunizing antigen in the right hind footpad on day 13, and the 24-hour delayed hypersensitivity response was assessed as percentage increase in footpad thickness. The low-protein diet reduced the inflammatory immune response, but JAWS cells, which exhibited immature phenotypic and functional characteristics, increased the response of both the malnourished group and the controls. By contrast, i.p. injection of 10(6) syngeneic T cells did not influence the inflammatory immune response of mice subjected to the low-protein protocol. Antigen-presenting cell numbers limited primary inflammatory cell-mediated competence in this model of wasting malnutrition, an outcome that challenges the prevailing multifactorial model of malnutrition-associated immune depression. Thus, a new dendritic cell-centered perspective emerges regarding the cellular mechanism underlying immune depression in acute pediatric protein and energy deficit.

Diagnosing environmental allergies: Comparison of skin-prick, intradermal, and serum specific immunoglobulin E testing

PubMed Central

Shtessel, Maria; Lobell, Elizabeth; Hudes, Golda; Rosenstreich, David; de Vos, Gabriele

2017-01-01

Background: Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. Objective: To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. Methods: SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. Results: A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357–4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. Conclusion: IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed. PMID:28583228

Use of intradermal dilutional testing and skin prick testing: clinical relevance and cost efficiency.

PubMed

Seshul, Merritt; Pillsbury, Harold; Eby, Thomas

2006-09-01

The objective was to determine the agreement of the positive results from a multiple skin prick test (SPT) device with the ability to determine a definable endpoint through intradermal dilutional testing (IDT) to compare semiquantitatively the degree of positivity of SPT results with quantitative results from IDT and to analyze the cost of immunotherapy based on SPT compared with IDT guided by SPT. Retrospective review of clinical data (random accrual). One hundred thirty-four patients underwent allergy screening using a multiple SPT device. Antigens testing positive by skin prick device were tested using IDT on a separate day. Antigens testing negative by SPT were not evaluated by IDT. Regional allergy testing practice patterns were determined, and a cost analysis using Medicare rates was performed There was good agreement between an antigen testing positive by SPT and the determination of a definable endpoint (93.33%, n = 1,334 antigens). The degree of positivity from the SPT correlated poorly with the final endpoint concentration (r = 0.40, P < .0001). Blended testing techniques were similar in cost when compared with several commonly used allergy testing protocols. Antigens which show reactivity to a multiple SPT device usually have a treatable endpoint that is independent of the degree of positivity of the SPT result. IDT is an important step in the determination of the strongest starting dose of immunotherapy that may be safely administered. Initiating immunotherapy in this manner may potentially create significant health care savings by shortening the time required for a patient to reach their individual maximally tolerated dose. The use of a relatively large screening panel is cost effective and does not increase the average number of antigens treated by immunotherapy. Blended allergy testing techniques that include IDT in their protocol are comparable in cost with commonly used allergy testing protocols.

Diagnosing environmental allergies: Comparison of skin-prick, intradermal, and serum specific immunoglobulin E testing.

PubMed

Ferastraoaru, Denisa; Shtessel, Maria; Lobell, Elizabeth; Hudes, Golda; Rosenstreich, David; de Vos, Gabriele

2017-06-01

Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357-4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed.

Prevalence and correlates of neck injection among people who inject drugs in Tijuana, Mexico.

PubMed

Rafful, Claudia; Wagner, Karla D; Werb, Dan; González-Zúñiga, Patricia E; Verdugo, Silvia; Rangel, Gudelia; Strathdee, Steffanie A

2015-11-01

Injecting drugs in the neck has been related to adverse health conditions such as jugular vein thrombosis, deep neck infections, aneurysm, haematomas, airway obstruction, vocal cord paralysis and wound botulism, among others. We identified prevalence and correlates of neck injection among people who inject drugs (PWID) in Tijuana, Mexico. Beginning in 2011, PWID aged ≥18 years who injected drugs within the last month were recruited into a prospective cohort. At baseline and semi-annually, PWID completed interviewer-administered surveys soliciting data on drug-injecting practices. Logistic regression was used to identify predictors of injecting in the neck as the most frequent injection site at a single visit. Of 380 PWID, 35.3% injected in the neck at least once in the past 6 months, among whom 71.6% reported it as their most common injection site, the most common injecting site after the arms (47%). Controlling for age, years injecting and injecting frequency, injecting heroin and methamphetamine two or more times per day and having sought injection assistance were associated with injecting in the neck [adjusted odds ratios (AOR): 2.12; 95% confidence intervals (CI): 1.27-3.53 and AOR: 2.65; 95% CI: 1.52-4.53 respectively]. Injecting in the neck was very common among PWID in Tijuana and was associated with polydrug use and seeking injection assistance. Tailoring harm reduction education interventions for individuals who provide injection assistance ('hit doctors') may allow for the dissemination of safe injecting knowledge to reduce injection-related morbidity and mortality. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Small-Volume Injections: Evaluation of Volume Administration Deviation From Intended Injection Volumes.

PubMed

Muffly, Matthew K; Chen, Michael I; Claure, Rebecca E; Drover, David R; Efron, Bradley; Fitch, William L; Hammer, Gregory B

2017-10-01

In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which small-volume injections (≤0.5 mL) deviated from the intended injection volumes among a group of pediatric anesthesiologists and pediatric postanesthesia care unit (PACU) nurses. We hypothesized that as the intended injection volumes decreased, the deviation from those intended injection volumes would increase. Ten attending pediatric anesthesiologists and 10 pediatric PACU nurses each performed a series of 10 injections into a simulated patient IV setup. Practitioners used separate 1-mL tuberculin syringes with removable 18-gauge needles (Becton-Dickinson & Company, Franklin Lakes, NJ) to aspirate 5 different volumes (0.025, 0.05, 0.1, 0.25, and 0.5 mL) of 0.25 mM Lucifer Yellow (LY) fluorescent dye constituted in saline (Sigma Aldrich, St. Louis, MO) from a rubber-stoppered vial. Each participant then injected the specified volume of LY fluorescent dye via a 3-way stopcock into IV tubing with free-flowing 0.9% sodium chloride (10 mL/min). The injected volume of LY fluorescent dye and 0.9% sodium chloride then drained into a collection vial for laboratory analysis. Microplate fluorescence wavelength detection (Infinite M1000; Tecan, Mannedorf, Switzerland) was used to measure the fluorescence of the collected fluid. Administered injection volumes were calculated based on the fluorescence of the collected fluid using a calibration curve of known LY volumes and associated fluorescence.To determine whether deviation of the administered volumes from the intended injection volumes increased at lower injection volumes, we compared the proportional injection volume error (loge [administered volume/intended volume]) for each of the 5 injection volumes using a linear

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

Rich catalytic injection

DOEpatents

Veninger, Albert [Coventry, CT

2008-12-30

A gas turbine engine includes a compressor, a rich catalytic injector, a combustor, and a turbine. The rich catalytic injector includes a rich catalytic device, a mixing zone, and an injection assembly. The injection assembly provides an interface between the mixing zone and the combustor. The injection assembly can inject diffusion fuel into the combustor, provides flame aerodynamic stabilization in the combustor, and may include an ignition device.

Anesthetic efficacy of a repeated intraosseous injection following a primary intraosseous injection.

PubMed

Jensen, Joanne; Nusstein, John; Drum, Melissa; Reader, Al; Beck, Mike

2008-02-01

The purpose of this prospective, randomized, single-blinded study was to determine the anesthetic efficacy of a repeated intraosseous injection given 30 minutes after a primary intraosseous injection. Using a crossover design, 55 subjects randomly received a primary X-tip intraosseous injection (Dentsply Inc, York, PA) of 1.4 mL of 2% lidocaine with epinephrine (using the Wand; Milestone Scientific, Deerfield, IL) and a repeated intraosseous or mock injection at 30 minutes in two appointments. The first molar and adjacent teeth were pulp tested every 2 minutes for a total of 120 minutes. Success was defined as obtaining two consecutive 80 readings with the electric pulp tester. Success of the initial intraosseous injection was 100% for the first molar. The repeated intraosseous injection mimicked the initial intraosseous injection in terms of pulpal anesthesia and statistically provided another 15 minutes of pulpal anesthesia. In conclusion, using the methodology presented, repeating the intraosseous injection 30 minutes after an initial intraosseous injection will provide an additional 15 minutes of pulpal anesthesia.

Prevalence and correlates of neck injection among people who inject drugs in Tijuana, Mexico

PubMed Central

RAFFUL, CLAUDIA; WAGNER, KARLA D.; WERB, DAN; GONZÁLEZ-ZÚÑIGA, PATRICIA E.; VERDUGO, SILVIA; RANGEL, GUDELIA; STRATHDEE, STEFFANIE A.

2016-01-01

Introduction and Aims Injecting drugs in the neck has been related to adverse health conditions such as jugular vein thrombosis, deep neck infections, aneurysm, haematomas, airway obstruction, vocal cord paralysis and wound botulism, among others. We identified prevalence and correlates of neck injection among people who inject drugs (PWID) in Tijuana, Mexico. Design and Methods Beginning in 2011, PWID aged ≥18 years who injected drugs within the last month were recruited into a prospective cohort. At baseline and semi-annually, PWID completed interviewer-administered surveys soliciting data on drug-injecting practices. Logistic regression was used to identify predictors of injecting in the neck as the most frequent injection site at a single visit. Results Of 380 PWID, 35.3% injected in the neck at least once in the past 6 months, among whom 71.6% reported it as their most common injection site, the most common injecting site after the arms (47%). Controlling for age, years injecting and injecting frequency, injecting heroin and methamphetamine two or more times per day and having sought injection assistance were associated with injecting in the neck [adjusted odds ratios (AOR): 2.12; 95% confidence intervals (CI): 1.27–3.53 and AOR: 2.65; 95% CI: 1.52–4.53 respectively]. Discussion and Conclusions Injecting in the neck was very common among PWID in Tijuana and was associated with polydrug use and seeking injection assistance. Tailoring harm reduction education interventions for individuals who provide injection assistance (‘hit doctors’) may allow for the dissemination of safe injecting knowledge to reduce injection-related morbidity and mortality. PMID:25867795

Experimental arthritis and uveitis in rats associated with Mycobacterium butyricum.

PubMed

Petty, R E; Hunt, D W; Mathers, D M; McCormick, A Q; Barker, H; Southwood, T R; Corson, L

1994-08-01

To determine if the anterior uveitis associated with adjuvant arthritis (AA) in the rat can be passively transferred with arthritis to syngeneic recipients using spleen cells or T cell lines prepared from animals given complete Freund's adjuvant (CFA) and Mycobacterium butyricum (M. butyricum) in incomplete Freund's adjuvant (IFA). Spleen cells from Lewis or Lewis SsN rats given IFA, CFA, type I collagen in IFA (CI-IFA), or type II collagen in IFA (CII-IFA) were administered to naive rats or rats treated with pertussis toxin or bacterial endotoxin. Three CD4+ T cell lines, propagated from CFA injected rats and maintained in vitro with M. butyricum (M-1), bovine proteoglycan (PR-1) or an extract of M. butyricum (MBE-1) were administered to naive or immunosuppressed rats. The arthritogenic and uveitogenic properties of these cell preparations and intradermal MBE-IFA, CII-IFA and intraperitoneal (ip) M. butyricum without adjuvant were evaluated. Uveitis was observed in 15/69 (22%) arthritic rats given CFA. Spleen cells prepared from CFA injected rats caused arthritis in 55 (82%) and uveitis in 2 (3%) of 67 cell recipients. Uveitis occurred in 2/6 cell recipients pretreated with bacterial endotoxin. Neither uveitis nor arthritis was observed in rats given IFA (0/6) or spleen cells prepared from rats given IFA (0/27), CI-IFA (0/6), or CII-IFA (0/28). CII-IFA produced polyarthritis in 5/6 rats, but no uveitis. CII-IFA induced arthritis associated uveitis in 1/15 animals receiving spleen cells from rats given CII-IFA, but not those given CI-IFA (0/3) or IFA (0/13). Uveitis was observed in one recipient of the M-1 T cell line and in 2 recipients of the PR-1 T cell line. Immunization with 400 micrograms of MBE-IFA induced uveitis but not arthritis in 3/11 animals. The MBE specific T cell line was neither arthritogenic nor uveitogenic. A high frequency (5/6) of uveitis accompanied arthritis in male Lewis rats given ip M. butyricum. Arthritis occurred in 4/10 female Lewis

Influence of pre-injection control parameters on main-injection fuel quantity for an electronically controlled double-valve fuel injection system of diesel engine

NASA Astrophysics Data System (ADS)

Song, Enzhe; Fan, Liyun; Chen, Chao; Dong, Quan; Ma, Xiuzhen; Bai, Yun

2013-09-01

A simulation model of an electronically controlled two solenoid valve fuel injection system for a diesel engine is established in the AMESim environment. The accuracy of the model is validated through comparison with experimental data. The influence of pre-injection control parameters on main-injection quantity under different control modes is analyzed. In the spill control valve mode, main-injection fuel quantity decreases gradually and then reaches a stable level because of the increase in multi-injection dwell time. In the needle control valve mode, main-injection fuel quantity increases with rising multi-injection dwell time; this effect becomes more obvious at high-speed revolutions and large main-injection pulse widths. Pre-injection pulse width has no obvious influence on main-injection quantity under the two control modes; the variation in main-injection quantity is in the range of 1 mm3.

RimabotulinumtoxinB Injection

MedlinePlus

... tightening of the neck muscles that may cause neck pain and abnormal head positions). RimabotulinumtoxinB injection is in ... cannot be substituted for another.RimabotulinumtoxinB injection controls ... longer before you feel the full benefit of rimabotulinumtoxinB injection.

Lacosamide Injection

MedlinePlus

Lacosamide injection is used in combination with other medications to control certain types of seizures in people who cannot take oral medications. Lacosamide injection is in a class of medications called ...

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

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 ...

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

Hydrocortisone Injection

MedlinePlus

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

Teduglutide Injection

MedlinePlus

... the medication should read the manufacturer's directions for mixing and injecting the medication before you use it ... Teduglutide must be used within 3 hours after mixing teduglutide powder with the diluent.You can inject ...

Doxycycline Injection

MedlinePlus

Doxycycline injection is used to treat or prevent bacterial infections, including pneumonia and other respiratory tract infections. ... certain skin, genital, intestine, and urinary system infections. Doxycycline injection may be used to treat or prevent ...

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 ...

Naltrexone Injection

MedlinePlus

Naltrexone injection is used along with counseling and social support to help people who have stopped drinking ... injection is also used along with counseling and social support to help people who have stopped abusing ...

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 ...

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 ...

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 ...

Tocilizumab Injection

MedlinePlus

... of age or older after receiving certain immunotherapy infusions. Tocilizumab injection is in a class of medications ... you miss an appointment to receive a tocilizumab infusion, call your doctor.If you forget to inject ...

Aripiprazole Injection

MedlinePlus

... a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or ... aripiprazole injection and aripiprazole extended-release injection developed gambling problems or other intense urges or behaviors that ...

Mipomersen Injection

MedlinePlus

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

Paclitaxel Injection

MedlinePlus

... other medications. Paclitaxel injection manufactured with polyoxyethylated castor oil is used to treat ovarian cancer (cancer that ... and lung cancer. Paclitaxel injection with polyoxyethylated castor oil is also used to treat Kaposi's sarcoma (a ...

Epidural steroid injections: update on efficacy, safety, and newer medications for injection.

PubMed

Kozlov, N; Benzon, H T; Malik, K

2015-08-01

The best evidence for epidural injection appears to be in the setting of radicular pain with epidural steroid and non-steroid injections more efficacious than non-epidural injections. Studies showed the efficacy of non-particulate steroid to approach the efficacy of particulate steroid and very limited comparisons demonstrated no significant difference between epidural steroid and epidural non-steroid (local anesthetic) injection. Preliminary studies evaluating epidural injection of disease modifying anti-rheumatic drugs such etanercept and tocilizumab showed conflicting results and had significant limitations. Randomized studies support better efficacy of transforaminal injection due to greater incidence of ventral epidural spread of injectate when compared to interlaminar injection. Thus, the transforaminal approach is recommended when unilateral radicular pain is limited to one nerve root. However, the transforaminal approach is associated with greater incidence of central nervous system injury, including paraplegia, attributed to embolization of the particulate steroid. Recent studies showed that non-particulate steroids potentially last as long as particulate steroids. Therefore non-particulate steroid should be used in initial transforaminal epidural injection. Future studies should look into the role of adjunct diagnostic aids, including digital subtraction angiography, in detecting intravascular injection and the ideal site of needle placement, whether it is the safe triangle or the triangle of Kambin. Finally, the role of epidural disease -modifying antirheumatic drugs in the management of back pain needs to be better elucidated.

Evaluation of three different histamine concentrations in intradermal testing of normal cats and attempted determination of 'irritant' threshold concentrations for 48 allergens.

PubMed

Austel, Michaela; Hensel, Patrick; Jackson, Dawn; Vidyashankar, Anand; Zhao, Ying; Medleau, Linda

2006-06-01

The purpose of this study was to determine the optimal histamine concentration and 'irritant' allergen threshold concentrations in intradermal testing (IDT) in normal cats. Thirty healthy cats were tested with three different histamine concentrations and four different concentrations of each allergen. The optimal histamine concentration was determined to be 1: 50,000 w/v (0.05 mg mL(-1)). Using this histamine concentration, the 'irritant' threshold concentration for most allergens was above the highest concentrations tested (4,000 PNU mL(-1) for 41 allergens and 700 PNU mL(-1) for human dander). The 'irritant' threshold concentration for flea antigen was determined to be 1:750 w/v. More than 10% of the tested cats showed positive reactions to Dermatophagoides farinae, Dermatophagoides pteronyssinus, housefly, mosquito and moth at every allergen concentration, which suggests that the 'irritant' threshold concentration for these allergens is below 1,000 PNU mL(-1), the lowest allergen concentration tested. Our results confirm previous studies in indicating that allergen and histamine concentrations used in feline IDT may need to be revised.

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.

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.

Pramlintide Injection

MedlinePlus

... eye problems. Using medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your ... inject pramlintide into your arm. Choose a different spot to inject pramlintide every day. Be sure that ...

Systemic Injection of Neural Stem/Progenitor Cells in Mice with Chronic EAE

PubMed Central

Donegà, Matteo; Giusto, Elena; Cossetti, Chiara; Schaeffer, Julia; Pluchino, Stefano

2014-01-01

Neural stem/precursor cells (NPCs) are a promising stem cell source for transplantation approaches aiming at brain repair or restoration in regenerative neurology. This directive has arisen from the extensive evidence that brain repair is achieved after focal or systemic NPC transplantation in several preclinical models of neurological diseases. These experimental data have identified the cell delivery route as one of the main hurdles of restorative stem cell therapies for brain diseases that requires urgent assessment. Intraparenchymal stem cell grafting represents a logical approach to those pathologies characterized by isolated and accessible brain lesions such as spinal cord injuries and Parkinson's disease. Unfortunately, this principle is poorly applicable to conditions characterized by a multifocal, inflammatory and disseminated (both in time and space) nature, including multiple sclerosis (MS). As such, brain targeting by systemic NPC delivery has become a low invasive and therapeutically efficacious protocol to deliver cells to the brain and spinal cord of rodents and nonhuman primates affected by experimental chronic inflammatory damage of the central nervous system (CNS). This alternative method of cell delivery relies on the NPC pathotropism, specifically their innate capacity to (i) sense the environment via functional cell adhesion molecules and inflammatory cytokine and chemokine receptors; (ii) cross the leaking anatomical barriers after intravenous (i.v.) or intracerebroventricular (i.c.v.) injection; (iii) accumulate at the level of multiple perivascular site(s) of inflammatory brain and spinal cord damage; and (i.v.) exert remarkable tissue trophic and immune regulatory effects onto different host target cells in vivo. Here we describe the methods that we have developed for the i.v. and i.c.v. delivery of syngeneic NPCs in mice with experimental autoimmune encephalomyelitis (EAE), as model of chronic CNS inflammatory demyelination, and envisage

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 ...

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 ( ...

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 ...

Buprenorphine Injection

MedlinePlus

Buprenorphine extended-release injection is used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic painkillers) ... sublingual buprenorphine for at least 7 days. Buprenorphine extended-release injection is in a class of medications ...

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 ...

Evolocumab Injection

MedlinePlus

... coronary artery bypass (CABG) surgery in people with cardiovascular disease. Evolocumab injection is also used along with diet ... evolocumab injection is used to treat HeFH or cardiovascular disease or to reduce the risk of a stroke, ...

Levoleucovorin Injection

MedlinePlus

... injection is used to prevent harmful effects of methotrexate (Rheumatrex, Trexall) when methotrexate is used to to treat certain types of ... people who have accidentally received an overdose of methotrexate or similar medications. Levoleucovorin injection is in a ...

Prevalence of injections and knowledge of safe injections among rural residents in Central China.

PubMed

Yan, Y W; Yan, J; Zhang, G P; Gao, Z L; Jian, H X

2007-08-01

Abuse of the injection services, namely unnecessary injections and unsafe injections, exists extensively in developing countries. Unsafe injection practices contribute to the transmission of blood-borne pathogens. The aims of this study were to survey the prevalence of injections and knowledge of injection safety among the rural residents in Jingzhou district, Hubei, China and to provide scientific data for developing a health educational programme. A retrospective cross-sectional study was conducted in 12 villages, which were selected from the Jingzhou district by the random sampling method. 50 rural residents were interviewed per village using a questionnaire. Among the 595 residents studied, 192 had received at least one injection in the past three months, with an injection prevalence of 32.3 percent and an average of 0.93 injections. 90.3 percent of the rural residents knew that unsafe injections could transmit the following blood-borne pathogens: human immunodeficiency virus (74.4 percent), hepatitis B virus (55.8 percent) and hepatitis C virus (22.9 percent). Logistic regression analysis showed that the residents' age, educational level and residential area were important factors in influencing their knowledge about injection safety. The results indicated that the injection prevalence was high among rural residents in the study area, and their knowledge regarding injection safety should be further improved.

An Innovative Needle-free Injection System: Comparison to 1 ml Standard Subcutaneous Injection.

PubMed

Kojic, Nikola; Goyal, Pragun; Lou, Cheryl Hamer; Corwin, Michael J

2017-11-01

A needle-free delivery system may lead to improved satisfaction and compliance, as well as reduced anxiety among patients requiring frequent or ongoing injections. This report describes a first-in-man assessment comparing Portal Instruments' innovative needle-free injection system with subcutaneous injections using a 27G needle. Forty healthy volunteer participants each received a total of four injections of 1.0 mL sterile saline solution, two with a standard subcutaneous injection using a 27G needle, and two using the Portal injection system. Perception of pain was measured using a 100-mm visual analog scale (VAS). Injection site reactions were assessed at 2 min and at 20-30 min after each injection. Follow-up contact was made 24-48 h after the injections. Subject preference regarding injection type was also assessed. VAS pain scores at Portal injection sites met the criteria to be considered non-inferior to the pain reported at 27G needle injection sites (i.e., upper 95% confidence bound less than +5 mm). Based on a mixed effects model, at time 0, accounting for potential confounding variables, the adjusted difference in VAS scores indicated that Portal injections were 6.5 mm lower than the 27G needle injections (95% CI -10.5, -2.5). No clinically important adverse events were noted. Portal injections were preferred by 24 (60%) of the subjects (P = 0.0015). As an early step in the development of this new needle-free delivery system, the current study has shown that a 1.0-mL saline injection can be given with less pain reported than a standard subcutaneous injection using a 27G needle.

Injection-controlled laser resonator

DOEpatents

Chang, J.J.

1995-07-18

A new injection-controlled laser resonator incorporates self-filtering and self-imaging characteristics with an efficient injection scheme. A low-divergence laser signal is injected into the resonator, which enables the injection signal to be converted to the desired resonator modes before the main laser pulse starts. This injection technique and resonator design enable the laser cavity to improve the quality of the injection signal through self-filtering before the main laser pulse starts. The self-imaging property of the present resonator reduces the cavity induced diffraction effects and, in turn, improves the laser beam quality. 5 figs.

Injection-controlled laser resonator

DOEpatents

Chang, Jim J.

1995-07-18

A new injection-controlled laser resonator incorporates self-filtering and self-imaging characteristics with an efficient injection scheme. A low-divergence laser signal is injected into the resonator, which enables the injection signal to be converted to the desired resonator modes before the main laser pulse starts. This injection technique and resonator design enable the laser cavity to improve the quality of the injection signal through self-filtering before the main laser pulse starts. The self-imaging property of the present resonator reduces the cavity induced diffraction effects and, in turn, improves the laser beam quality.

Continuous in vivo infusion of interferon-gamma (IFN-γ) enhances engraftment of syngeneic wild-type cells in Fanca–/– and Fancg–/– mice

PubMed Central

Si, Yue; Ciccone, Samantha; Yang, Feng-Chun; Yuan, Jin; Zeng, Daisy; Chen, Shi; van de Vrugt, Henri J.; Critser, John; Arwert, Fre; Haneline, Laura S.; Clapp, D. Wade

2006-01-01

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc–/– cells to interferon-gamma (IFN-γ), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc–/– mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca–/– and Fancg–/– mice are hypersensitive to IFN-γ and that in vivo infusion of IFN-γ at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-γ conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients. PMID:16946306

Degarelix Injection

MedlinePlus

... 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) receptor antagonists. It works by decreasing the amount of ...

Indian Injection Technique Study: Injecting Complications, Education, and the Health Care Professional.

PubMed

Kalra, Sanjay; Mithal, Ambrish; Sahay, Rakesh; John, Mathew; Unnikrishnan, A G; Saboo, Banshi; Ghosh, Sujoy; Sanyal, Debmalya; Hirsch, Laurence J; Gupta, Vandita; Strauss, Kenneth W

2017-06-01

Using the Indian and rest of world (ROW) injection technique questionnaire (ITQ) data, we address key insulin injection complications. In 2015 we conducted an ITQ survey throughout India involving 1011 patients. Indian values were compared with those from 41 other countries participating in the ITQ, known here as ROW. More than a quarter of Indian insulin users described lesions consistent with lipohypertrophy (LH) at their injection sites and approximately 1 in 5 were found to have LH by the examining nurse (using visual inspection and palpation). Just over half of Indian injectors report having pain on injection. Of these, 4 out of 5 report having painful injections only several times a month or year (i.e., not with every injection). Doctors and diabetes educators in India (as opposed to nurses) have a larger role in teaching patients how to inject than they do in ROW. Despite this specialized approach, a very high percentage of patients report that they have not been trained (at least cannot remember being trained) in a wide range of essential injection topics. Only about 30% of Indian injectors get their sites checked at least annually, with nearly a third only having sites checked when they specifically complained and nearly 4 out of 10 never having had their sites checked. Indian HCPs can clearly do a better job covering all the vital topics essential to proper injection habits.

Ixekizumab Injection

MedlinePlus

... or runny nose redness or pain at the injection site abdominal pain diarrhea (with or without blood) weight loss Some side effects can be serious. If you experience any of these symptoms ... ixekizumab injection and call your doctor immediately or get emergency ...

Zidovudine Injection

MedlinePlus

... immunodeficiency virus (HIV) infection. Zidovudine is given to HIV-positive pregnant women to reduce the chance of passing the infection to the baby. Zidovudine injection is in a class of medications ... the amount of HIV in the blood. Although zidovudine injection does not ...

Sonographically guided deep plantar fascia injections: where does the injectate go?

PubMed

Maida, Eugene; Presley, James C; Murthy, Naveen; Pawlina, Wojciech; Smith, Jay

2013-08-01

To determine the distribution of sonographically guided deep plantar fascia injections in an unembalmed cadaveric model. A single experienced operator completed 10 sonographically guided deep plantar fascia injections in 10 unembalmed cadaveric specimens (5 right and 5 left) obtained from 6 donors (2 male and 4 female) aged 49 to 95 years (mean, 77.5 years) with a mean body mass index of 23.2 kg/m(2) (range, 18.4-26.3 kg/m(2)). A 12-3-MHz linear array transducer was used to direct a 22-gauge, 38-mm stainless steel needle deep to the plantar fascia at the anterior aspect of the calcaneus using an in-plane, medial-to-lateral approach. In each case, 1.5 mL of 50% diluted colored latex was injected deep to the plantar fascia. After a minimum of 72 hours, study coinvestigators dissected each specimen to assess injectate placement. All 10 injections accurately placed latex adjacent to the deep side of the plantar fascia at the anterior calcaneus. However, the flexor digitorum brevis (FDB) origin from the plantar fascia variably limited direct latex contact with the plantar fascia, and small amounts of latex interdigitated with the FDB origin in 90% (9 of 10). In all 10 specimens, latex also covered the traversing first branch of the lateral plantar nerve (FBLPN, ie, Baxter nerve) between the FDB and quadratus plantae muscles. No latex was found in the plantar fat pad or plantar fascia in any specimen. Sonographically guided deep plantar fascia injections reliably deliver latex deep to the plantar fascia while avoiding intrafascial injection. However, the extent of direct plantar fascia contact is variable due to the intervening FDB. On the contrary, the traversing FBLPN is reliably covered by the injection. Deep plantar fascia injections may have a role in the management of refractory plantar fasciitis, particularly following failed superficial perifascial or intrafascial injections, in cases of preferential deep plantar fascia involvement, or when entrapment

Cold urticaria: inhibition of cold-induced histamine release by doxantrazole.

PubMed

Bentley-Phillips, C B; Eady, R A; Greaves, M W

1978-10-01

Thirteen patients with cold urticaria were studied to assess the effect of the systemic drug doxantrazole, which has actions resembling disodium cromoglycate, on cold evoked histamine release. The patients, all of whom developed an immediate local whealing response after cooling of the forearm, demonstrated release of histamine into venous blood draining that forearm. Following doxantrazole treatment, significant suppression of histamine release occurred. In some but not all patients this was accompanied by diminution of urtication in response to cooling. A double-blind study was carried out in 3 subjects, all of whom showed diminished cold-stimulated histamine release after doxantrazole. Two of these showed clinical improvement. Doxantrazole had no effect on erythema due to intradermal histamine, but did suppress the erythematous reaction to intradermal injection of compound 48/80. Our results suggest that doxantrazole or related anti-allergic agents might be useful in the treatment of cold urticaria.

In vivo immunologic selection of class I major histocompatibility complex gene deletion variants from the B16-BL6 melanoma.

PubMed

Talmadge, J E; Talmadge, C B; Zbar, B; McEwen, R; Meeker, A K; Tribble, H

1987-06-01

The mechanism by which tumor allografts escape host immunologic attack was investigated. B16-BL6 cells (the bladder 6 subline of the B16 melanoma) (H-2b) were transfected with a gene (Dd) encoding an allogeneic class I major histocompatibility complex antigen. Clones that expressed Dd antigen were injected into the footpads of nonimmune syngeneic mice, syngeneic immune mice, and nude mice. Under conditions of immunologic selection a clone that contained multiple copies of the transfected gene formed variants that lacked the transfected gene. Primary tumors and pulmonary metastases of immunized mice and pulmonary metastases of nonimmunized mice had lost the Dd gene and, in most cases, all of the associated plasmid. In contrast, in immunodeficient nude mice, primary tumors and pulmonary metastases retained the Dd gene and the associated plasmid. Deletion of genes encoding cell surface antigens may be one of the mechanisms by which allogeneic tumors escape immunologic attack.

Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells.

PubMed

Dong, Lan-Feng; Kovarova, Jaromira; Bajzikova, Martina; Bezawork-Geleta, Ayenachew; Svec, David; Endaya, Berwini; Sachaphibulkij, Karishma; Coelho, Ana R; Sebkova, Natasa; Ruzickova, Anna; Tan, An S; Kluckova, Katarina; Judasova, Kristyna; Zamecnikova, Katerina; Rychtarcikova, Zuzana; Gopalan, Vinod; Andera, Ladislav; Sobol, Margarita; Yan, Bing; Pattnaik, Bijay; Bhatraju, Naveen; Truksa, Jaroslav; Stopka, Pavel; Hozak, Pavel; Lam, Alfred K; Sedlacek, Radislav; Oliveira, Paulo J; Kubista, Mikael; Agrawal, Anurag; Dvorakova-Hortova, Katerina; Rohlena, Jakub; Berridge, Michael V; Neuzil, Jiri

2017-02-15

Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ 0 cells) is linked to the acquisition of the host mtDNA. However, the mechanism of mtDNA movement between cells remains unresolved. To determine whether the transfer of mtDNA involves whole mitochondria, we injected B16ρ 0 mouse melanoma cells into syngeneic C57BL/6N su9-DsRed2 mice that express red fluorescent protein in their mitochondria. We document that mtDNA is acquired by transfer of whole mitochondria from the host animal, leading to normalisation of mitochondrial respiration. Additionally, knockdown of key mitochondrial complex I (NDUFV1) and complex II (SDHC) subunits by shRNA in B16ρ 0 cells abolished or significantly retarded their ability to form tumours. Collectively, these results show that intact mitochondria with their mtDNA payload are transferred in the developing tumour, and provide functional evidence for an essential role of oxidative phosphorylation in cancer.

A Co-Drug of Butyric Acid Derived from Fermentation Metabolites of the Human Skin Microbiome Stimulates Adipogenic Differentiation of Adipose-Derived Stem Cells: Implications in Tissue Augmentation.

PubMed

Wang, Yanhan; Zhang, Lingjuan; Yu, Jinghua; Huang, Stephen; Wang, Zhenping; Chun, Kimberly Ann; Lee, Tammy Ling; Chen, Ying-Tung; Gallo, Richard L; Huang, Chun-Ming

2017-01-01

We show that Staphylococcus epidermidis, a commensal bacterium in the human skin microbiome, produces short-chain fatty acids by glycerol fermentation that can induce adipogenesis. Although the antimicrobial and anti-inflammatory activities of short-chain fatty acids have been previously well characterized, little is known about the contribution of short-chain fatty acids to the adipogenic differentiation of adipose-derived stem cells (ADSCs). We show that ADSCs differentiated into adipocytes and accumulated lipids in the cytoplasm when cultured with butyric acid, a principal short-chain fatty acid in the fermentation metabolites of S. epidermidis. Additionally, a co-drug, butyric acid 2-(2-butyryloxyethoxy) ethyl ester (BA-DEG-BA), released active butyric acid when it was intradermally injected into mouse ears and induced ADSC differentiation, characterized by an increased expression of cytoplasmic lipids and perilipin A. The BA-DEG-BA-induced adipogenic differentiation was mediated via peroxisome proliferator-activated receptor gamma. Furthermore, intradermal injection of ADSCs along with BA-DEG-BA into mouse ears markedly enhanced the adipogenic differentiation of ADSCs, leading to dermal augmentation. Our study introduces BA-DEG-BA as an enhancer of ADSC adipogenesis and suggests an integral interaction between the human skin microbiome and ADSCs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Treatment of wrinkles of the upper lip by emulsified fat or "Nanofat": Biological and clinical study about 4 cases].

PubMed

Mesguich Batel, F; Bertrand, B; Magalon, J; François, P; Velier, M; Veran, J; Mallet, S; Jouve, E; Sabatier, F; Casanova, D

2018-02-01

Emulsified fat injection showed its interest in aesthetic facial surgery. The adipose tissue harvested is mechanically emulsified and filtered. The suspension obtained is injected into the dermis through small diameter needles (27 to 30 gauges). The objective of our study was to evaluate the biological composition of emulsified fat and its clinical effectiveness in the treatment of peri-oral wrinkles in 4 patients aged 50 to 59 years. Each patient received an intradermal injection of emulsified fat in the peri-oral wrinkles prepared from abdominal fat under local anesthesia. The cell viability, stromal vascular fraction (FVS) composition in emulsified fat and the adipocyte differentiation capacity of mesenchymal stem cells (MSC) were studied. The clinical results were evaluated by standardized photographs, 3D microphotography, confocal microscopy, and self-evaluation of patient satisfaction over a period of 4 months. The biological study of the emulsified fat found a lysis of all the adipocytes. The mean number of FVS cells was 126,330±2758 cells by cc of emulsified fat with preserved cell viability (85.1±6.84 %) and a good proportion of regeneratives cells (18.77±6.2 %). The clinical study found a tendency to decrease the volume of wrinkles on standardized photography and 3D microphotography no significative. Patients were satisfied with treatment with an average score of 7±1.15/10 to 4 months. Intradermal injection of emulsified fat seems to be an interesting treatment of face wrinkles. Our study has shown its safety, but additional studies seems necessary to confirm its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Systemic cell-mediated reactions in vivo. Effect of the interaction of circulating antigen with sensitized lymphocytes on glomeruli and pulmonary alveoli.

PubMed Central

Bhan, A. K.; Schneeberger, E. E.; Collins, A. B.; McCluskey, R. T.

1984-01-01

The effects of systemic cell-mediated hypersensitivity reactions on glomeruli and lungs were investigated in rats. The animals were given an intravenous injection of antigen 7 days after sensitization or were given an intravenous injection of lymph node cells from sensitized syngeneic donors 1 day after antigen injection. Control animals were given an irrelevant antigen or saline. All animals received three injections of 3H-thymidine during the course of the experiments. The animals were sacrificed 2 or 3 days after antigen injection. Autoradiographs of renal and pulmonary tissue showed significantly more labeled mononuclear cells in glomeruli and pulmonary alveolar walls in the experimental groups than in the control groups. Immunofluorescence studies did not reveal antigen, rat IgG, or C3 in glomeruli. The results indicate that systemic cell-mediated reactions can lead to an accumulation of mononuclear cells in glomeruli and lungs, an effect that may contribute to tissue injury. Images Figure 1 Figure 2 Figure 3 PMID:6611090

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). Copyright © 2014 The Authors

Antigen-induced inhibition of autoimmune response to rat male accessory glands: distinct characteristics of I-A- and I-E-positive peritoneal cells.

PubMed

Rivero, V E; Ferro, M E; Romero-Piffiguer, M; Correa, S; Yranzo-Volonté, N; Riera, C M

1991-05-01

The present report describes different aspects of two populations of peritoneal cells (PC) obtained from rats injected i.p. 2 h or 24 h previously with a suppressor dose of a purified fraction (FI) of rat male accessory glands (RAG) (FI-PC2h and FI-PC24h, respectively). The FI-PC2h, which are mainly I-E (OX17) positive and can suppress the autoimmune response to RAG autoantigens, have an elevated phagocytic activity against Candida albicans and capacity to reduce the dye nitroblue tetrazolium. In contrast, FI-PC24h, which are mainly I-A (OX6) positive and can potentiate the autoimmunity to RAG autoantigens, have a diminished capacity to reduce the dye and a diminished phagocytic activity. Moreover, the Toxoplasma gondii appear to have a different effect on both populations. The parasites can invade FI-PC2h while FI-PC24h offer resistance to T. gondii aggression. FI-PC2h cultured during 22 h (FI-PC2-24h in vitro), or PC obtained from syngeneic recipients injected i.p. 22 h previously with FI-PC2h (FI-PC2-24h in vivo) show, as FI-PC2h, an increase of the I-E+ cells and capacity to induce suppression of the delayed-type hypersensitivity response to RAG autoantigens when they are injected to syngeneic rats 10 and 3 days prior to the immunization with chemically modified (diazotized arsanilic and sulfanilic acid) RAG in complete Freund's adjuvant. The PC obtained 24 h after injection of irradiated rats with N-PC plus FI show an increase of I-E+ cells whereas an enhancement of I-A+ cells can be observed when the PC are obtained 24 h after injection of irradiated and bone marrow-reconstituted rats with N-PC plus FI. These findings appear to indicate that FI-PC2h and FI-PC24h are functionally different and that the population obtained 24 h after injection of FI of RAG could not originate from either the population present 2 h after injection of FI of RAG injection nor from normal PC. They appear to require bone marrow precursors.

Injectable Drug Eluting Elastomeric Polymer: A Novel Submucosal Injection Material

PubMed Central

Tran, Richard T.; Palmer, Michael; Tang, Shou-Jiang; Abell, Thomas L.; Yang, Jian

2011-01-01

Background Biodegradable hydrogels can deliver therapeutic payloads with great potentials in endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) to yield improvements in efficacy and foster mucosal regeneration. Objective To assess the efficacy of an injectable drug eluting elastomeric polymer (iDEEP) as a submucosal injection material. Design Comparative study among 3 different solutions using material characterization tests, ex vivo and in vivo porcine models. Setting Academic hospital. Interventions 30 gastric submucosal cushions were achieved with saline (0.9%), sodium hyaluronate (0.4%), and iDEEP (n = 10) in ex vivo porcine stomachs. Four porcine gastric submucosal cushions were then performed in vivo using iDEEP. Main outcome measurements Maximum injection pressure, Rebamipide release rate, submucosal elevation duration, and assessment of in vivo efficacy by en bloc resection. Results No significant difference in injection pressures between iDEEP (28.9 ± 0.3 PSI) and sodium hyaluronate (29.5 ± 0.4 PSI, P > .05) was observed. iDEEP gels displayed a controlled release of Rebamipide up to 2 weeks in vitro. The elevation height of iDEEP (5.7 ± 0.5 mm) was higher than saline (2.8 ± 0.2 mm, P < .01) and SH (4.2 ± 0.2 mm, P < .05). All EMR procedures were successfully performed after injection of iDEEP, and a large gel cushion was noted after the resection procedure. Limitations Benchtop, ex vivo, and non-survival pig study. Conclusions A novel injection solution was evaluated for endoscopic resection. These results suggest that iDEEP may provide a significant step towards the realization of an ideal EMR and ESD injection material. PMID:22301346

The longitudinal association between homelessness, injection drug use, and injection-related risk behavior among persons with a history of injection drug use in Baltimore, MD.

PubMed

Linton, Sabriya L; Celentano, David D; Kirk, Gregory D; Mehta, Shruti H

2013-10-01

Few studies have assessed the temporal association between homelessness and injection drug use, and injection-related risk behavior. Among a cohort of 1405 current and former injection drug users in follow-up from 2005 to 2009, we used random intercept models to assess the temporal association between homelessness and subsequent injection drug use, and to determine whether the association between homelessness and sustained injection drug use among active injectors differed from the association between homelessness and relapse among those who stopped injecting. We also assessed the association between homelessness and subsequent injection-related risk behavior among participants who injected drugs consecutively across two visits. Homelessness was categorized by duration: none, <1 month, and ≥1 month. Homelessness was reported on at least one occasion by 532 (38%) participants. The relationship between homelessness and subsequent injection drug use was different for active injectors and those who stopped injecting. Among those who stopped injecting, homelessness was associated with relapse [<1 month: AOR=1.67, 95% CI (1.01, 2.74); ≥1 month: AOR=1.34 95% CI (0.77, 2.33)]. Among active injectors, homelessness was not associated with sustained injection drug use [<1 month: AOR=1.03, 95% CI (0.71, 1.49); ≥1 month: AOR=0.81 95% CI (0.56, 1.17)]. Among those injecting drugs across two consecutive visits, homelessness ≥1 month was associated with subsequent injection-related risk behavior [AOR=1.61, 95% CI (1.06, 2.45)]. Homelessness appears to be associated with relapse and injection-related risk behavior. Strengthening policies and interventions that prevent homelessness may reduce injection drug use and injection-related risk behaviors. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Quantitative genetic analysis of the bTB diagnostic single intradermal comparative cervical test (SICCT).

PubMed

Tsairidou, Smaragda; Brotherstone, Susan; Coffey, Mike; Bishop, Stephen C; Woolliams, John A

2016-11-24

Bovine tuberculosis (bTB) is a disease of significant economic importance and is a persistent animal health problem with implications for public health worldwide. Control of bTB in the UK has relied on diagnosis through the single intradermal comparative cervical test (SICCT). However, limitations in the sensitivity of this test hinder successful eradication and the control of bTB remains a major challenge. Genetic selection for cattle that are more resistant to bTB infection can assist in bTB control. The aim of this study was to conduct a quantitative genetic analysis of SICCT measurements collected during bTB herd testing. Genetic selection for bTB resistance will be partially informed by SICCT-based diagnosis; therefore it is important to know whether, in addition to increasing bTB resistance, this might also alter genetically the epidemiological characteristics of SICCT. Our main findings are that: (1) the SICCT test is robust at the genetic level, since its hierarchy and comparative nature provide substantial protection against random genetic changes that arise from genetic drift and from correlated responses among its components due to either natural or artificial selection; (2) the comparative nature of SICCT provides effective control for initial skin thickness and age-dependent differences; and (3) continuous variation in SICCT is only lowly heritable and has a weak correlation with SICCT positivity among healthy animals which was not significantly different from zero (P > 0.05). These emerging results demonstrate that genetic selection for bTB resistance is unlikely to change the probability of correctly identifying non-infected animals, i.e. the test's specificity, while reducing the overall number of cases. This study cannot exclude all theoretical risks from selection on resistance to bTB infection but the role of SICCT in disease control is unlikely to be rapidly undermined, with any adverse correlated responses expected to be weak and slow, which

Experiment Research of Microbial Flooding Injected Capacity and Injected Volume

NASA Astrophysics Data System (ADS)

Shi, Fang; Zhao, Yang; Tang, Qinghua; Xie, Ximing

2018-01-01

Strains of microbial enhanced oil recovery technology is the use of crude oil directly in growth and the same time the metabolites of itself, so as to enhance oil recovery. Experimental study on paper through a number of data analysis. The growth and metabolism of three kinds of oil producing bacteria in the core are determined, and the corresponding growth curve is obtained. The parameter sensitivity analysis of the microorganism flooding process by homogeneous core is studied, and the influence of injection capacity and injection volume on the oil displacement effect is studied. The same permeability, water, temperature and other conditions, microbial injection pressure has a certain degree of increase than water flooding. Injection volume depends on the actual input-output ratio, quantity is 0.3PV is more reasonable.

Fibered Confocal Fluorescence Microscopy for the Noninvasive Imaging of Langerhans Cells in Macaques.

PubMed

Todorova, Biliana; Salabert, Nina; Tricot, Sabine; Boisgard, Raphaël; Rathaux, Mélanie; Le Grand, Roger; Chapon, Catherine

2017-01-01

We developed a new approach to visualize skin Langerhans cells by in vivo fluorescence imaging in nonhuman primates. Macaques were intradermally injected with a monoclonal, fluorescently labeled antibody against HLA-DR molecule and were imaged for up to 5 days by fibered confocal microscopy (FCFM). The network of skin Langerhans cells was visualized by in vivo fibered confocal fluorescence microscopy. Quantification of Langerhans cells revealed no changes to cell density with time. Ex vivo experiments confirmed that injected fluorescent HLA-DR antibody specifically targeted Langerhans cells in the epidermis. This study demonstrates the feasibility of single-cell, in vivo imaging as a noninvasive technique to track Langerhans cells in nontransgenic animals.

Relationship Between the Provision of Injection Services in Ambulatory Physician Offices and Prescribing Injectable Medicines.

PubMed

Yousefi, Naeimeh; Rashidian, Arash; Soleymani, Fatemeh; Kebriaeezade, Abbas

2017-01-01

Overuse of injections is a common problem in many low-income and middle income countries. While cultural factors and attitudes of both physicians and patients are important factors, physicians› financial intensives may play an important role in overprescribing of injections. This study was designed to assess the effects of providing injection- services in physicians› ambulatory offices on prescribing injectable medicines. This cross-sectional study was conducted in Tehran in 2012 -2013and included a random sample of general physicians, pediatricians and infectious disease specialists. We collected data on the provision of injection services in or in proximity of physician offices, and obtained data from physicians› prescriptions in the previous three-month period. We analyzed the data using ANOVA, Student›s t-test and linear regression methods. We obtained complete data from 465 of 600 sampled physicians. Overall 41.9% of prescriptions contained injectable medicines. 75% of physicians offered injection services in their offices. Male physicians and general physicians were more likely to offer the services, and more likely to prescribe injectables. We observed a clear linear relationship between the injection service working hours and the proportion of prescriptions containing injectables (p-value<0.001). Providing injection service in the office was directly linked with the proportion of prescriptions containing injectables. While provision of injection services may provide a direct financial benefit to physicians, it is unlikely to be able to substantially reduce injectable medicines› prescription without addressing the issue.

Compressed air injection technique to standardize block injection pressures : [La technique d'injection d'air comprimé pour normaliser les pressions d'injection d'un blocage nerveux].

PubMed

Tsui, Ban C H; Li, Lisa X Y; Pillay, Jennifer J

2006-11-01

Presently, no standardized technique exists to monitor injection pressures during peripheral nerve blocks. Our objective was to determine if a compressed air injection technique, using an in vitro model based on Boyle's law and typical regional anesthesia equipment, could consistently maintain injection pressures below a 1293 mmHg level associated with clinically significant nerve injury. Injection pressures for 20 and 30 mL syringes with various needle sizes ( 18G, 20G, 21 G, 22G, and 24G) were measured in a closed system. A set volume of air was aspirated into a saline-filled syringe and then compressed and maintained at various percentages while pressure was measured. The needle was inserted into the injection port of a pressure sensor, which had attached extension tubing with an injection plug clamped "off". Using linear regression with all data points, the pressure value and 99% confidence interval (CI) at 50% air compression was estimated. The linearity of Boyle's law was demonstrated with a high correlation, r = 0.99, and a slope of 0.984 (99% CI: 0.967-1.001). The net pressure generated at 50% compression was estimated as 744.8 mmHg, with the 99% CI between 729.6 and 760.0 mmHg. The various syringe/needle combinations had similar results. By creating and maintaining syringe air compression at 50% or less, injection pressures will be substantially below the 1293 mmHg threshold considered to be an associated risk factor for clinically significant nerve injury. This technique may allow simple, real-time and objective monitoring during local anesthetic injections while inherently reducing injection speed. Présentement, aucune technique normalisée ne permet de vérifier les pressions d'injection pendant les blocages nerveux périphériques. Nous voulions vérifier si une technique d'injection d'air comprimé, utilisant un modèle in vitro fondé sur la loi de Boyle et du matériel propre à l'anesthésie régionale, pouvait maintenir avec régularité les

Calculation method of water injection forward modeling and inversion process in oilfield water injection network

NASA Astrophysics Data System (ADS)

Liu, Long; Liu, Wei

2018-04-01

A forward modeling and inversion algorithm is adopted in order to determine the water injection plan in the oilfield water injection network. The main idea of the algorithm is shown as follows: firstly, the oilfield water injection network is inversely calculated. The pumping station demand flow is calculated. Then, forward modeling calculation is carried out for judging whether all water injection wells meet the requirements of injection allocation or not. If all water injection wells meet the requirements of injection allocation, calculation is stopped, otherwise the demand injection allocation flow rate of certain step size is reduced aiming at water injection wells which do not meet requirements, and next iterative operation is started. It is not necessary to list the algorithm into water injection network system algorithm, which can be realized easily. Iterative method is used, which is suitable for computer programming. Experimental result shows that the algorithm is fast and accurate.

Relationships between Induced Seismicity and Fluid Injection: Development of Strategies to Manage Injection

NASA Astrophysics Data System (ADS)

Eichhubl, Peter; Frohlich, Cliff; Gale, Julia; Olson, Jon; Fan, Zhiqiang; Gono, Valerie

2014-05-01

Induced seismicity during or following the subsurface injection of waste fluids such as well stimulation flow back and production fluids has recently received heightened public and industry attention. It is understood that induced seismicity occurs by reactivation of existing faults that are generally present in the injection intervals. We seek to address the question why fluid injection triggers earthquakes in some areas and not in others, with the aim toward improved injection methods that optimize injection volume and cost while avoiding induced seismicity. A GIS database has been built of natural and induced earthquakes in four hydrocarbon-producing basins: the Fort Worth Basin, South Texas, East Texas/Louisiana, and the Williston Basin. These areas are associated with disposal from the Barnett, Eagle Ford, Bakken, and Haynesville Shales respectively. In each region we analyzed data that were been collected using temporary seismographs of the National Science Foundation's USArray Transportable Array. Injection well locations, formations, histories, and volumes are also mapped using public and licensed datasets. Faults are mapped at a range of scales for selected areas that show different levels of seismic activity, and scaling relationships used to extrapolate between the seismic and wellbore scale. Reactivation potential of these faults is assessed using fault occurrence, and in-situ stress conditions, identifying areas of high and low fault reactivation potential. A correlation analysis between fault reactivation potential, induced seismicity, and fluid injection will use spatial statistics to quantify the probability of seismic fault reactivation for a given injection pressure in the studied reservoirs. The limiting conditions inducing fault reactivation will be compared to actual injection parameters (volume, rate, injection duration and frequency) where available. The objective of this project is a statistical reservoir- to basin-scale assessment of fault

Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma.

PubMed

Yasuda, Takashi; Kamigaki, Takashi; Kawasaki, Kentaro; Nakamura, Tetsu; Yamamoto, Masashi; Kanemitsu, Kiyonori; Takase, Shiro; Kuroda, Daisuke; Kim, Yongsik; Ajiki, Tetsuo; Kuroda, Yoshikazu

2007-07-01

Cancer immunotherapy by dendritic cell (DC)/tumor cell fusion hybrids (DC/TC hybrids) has been shown to elicit potent anti-tumor effects via the induction of immune responses against multiple tumor-associated antigens. In the present study, we compared the anti-tumor effects of vaccinating Balb/c mice (H-2(d)) with CT26CL25 colon carcinoma cells that had been fused with either syngeneic DCs from Balb/c mice, allogeneic DCs from C57BL/6 mice (H-2(b)) or semiallogeneic DCs from B6D2F1 mice (H-2(b/d)). Preimmunization with either semiallogeneic or allogeneic DC/TC hybrids induced complete protection from tumor challenge, whereas mice preimmunized with syngeneic DC/TC hybrids were only partially protected (75% tumor rejection). The average number of pulmonary metastases after intravenous tumor injection decreased significantly following immunization with semiallogeneic or allogeneic DC/TC hybrids (8.3 +/- 7.9 or 16.3 +/- 3.5, mean +/- SD) relative to syngeneic DC/TC hybrids (67.8 +/- 6.3). These data demonstrate that vaccination with semiallogeneic DC/TC hybrids resulted in the greatest anti-tumor efficacy. Anti-tumor effects showed by in vivo studies were virtually accomplished by the frequency of induced CTLs specific to both gp70 and beta-galactosidase assessed by using pentameric assay. Among the fusion vaccines tested, semiallogeneic DC/TC hybrids induced the highest ratio of Th1 cytokine IFN-gamma to Th2 cytokine IL-10. In addition, allogeneic or semiallogeneic DC/TC hybrids elicited a significantly stronger NK activity than syngeneic DC/TC hybrids. These findings suggest that in clinical settings, DCs derived from a healthy donor (which are generally characterized as more semiallogeneic than allogeneic) may be more capable than autologous DCs of inducing promising anti-tumor effects in vaccinations with DC/TC hybrids.

Strategies for safe injections.

PubMed Central

Battersby, A.; Feilden, R.; Stoeckel, P.; Da Silva, A.; Nelson, C.; Bass, A.

1999-01-01

In 1998, faced with growing international concern, WHO set out an approach for achieving injection safety that encompassed all elements from patients' expectations and doctors' prescribing habits to waste disposal. This article follows that lead and describes the implications of the approach for two injection technologies: sterilizable and disposable. It argues that focusing on any single technology diverts attention from the more fundamental need for health services to develop their own comprehensive strategies for safe injections. National health authorities will only be able to ensure that injections are administered safely if they take an approach that encompasses the whole system, and choose injection technologies that fit their circumstances. PMID:10680247

Distribution and regularity of injection from a multicylinder fuel-injection pump

NASA Technical Reports Server (NTRS)

Rothrock, A M; Marsh, E T

1936-01-01

This report presents the results of performance test conducted on a six-cylinder commercial fuel-injection pump that was adjusted to give uniform fuel distribution among the cylinders at a throttle setting of 0.00038 pound per injection and a pump speed of 750 revolutions per minute. The throttle setting and pump speed were then varied through the operating range to determine the uniformity of distribution and regularity of injection.

Penicillin G Procaine Injection

MedlinePlus

Penicillin G procaine injection is used to treat certain infections caused by bacteria. Penicillin G procaine injection should not be used to ... early in the treatment of certain serious infections. Penicillin G procaine injection is in a class of ...

Supersonic Pulsed Injection

NASA Technical Reports Server (NTRS)

Cutler, A. D.; Harding, G. C.; Diskin, G. S.

2001-01-01

An injector has been developed to provide high-speed high-frequency (order 10 kHz) pulsed a supersonic crossflow. The injector nozzle is formed between the fixed internal surface of the nozzle and a freely rotating three- or four-sided wheel embedded within the device. Flow-induced rotation of the wheel causes the nozzle throat to open and close at a frequency proportional to the speed of sound of the injected gas. Measurements of frequency and mass flow rate as a function of supply pressure are discussed for various injector designs. Preliminary results are presented for wall-normal injection of helium into a Mach-2 ducted airflow. The data include schlieren images in the injectant plume in a plane normal to the flow, downstream of injection.

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 ...

Human histology and persistence of various injectable filler substances for soft tissue augmentation.

PubMed

Lemperle, Gottfried; Morhenn, Vera; Charrier, Ulrich

2003-01-01

An increasing number of soft tissue filler substances have been introduced to the beauty market outside the U.S. which lack experimental and clinical data in support of their claim. Ten commercially available filler substances were examined for biocompatibility and durability: 0.1 cc of each substance was injected deep intradermally into the volar forearm of one of the authors and observed for clinical reaction and permanence. At 1, 3, 6, and 9 months the test sites were excised, histologically examined, and graded according to foreign body reactions classification. Collagen (Zyplast) was phagocytosed at 6 months and hyaluronic acid (Restylane) at 9 months. PMMA microspheres (Artecoll) had encapsulated with connective tissue, macrophages, and sporadic giant cells. Silicone oil (PMS 350) was clinically inconspicuous but dissipated into the tissue, causing a chronic foreign body reaction. Polylactic acid microspheres (New-Fill) induced a mild inflammatory response and had disappeared clinically at 4 months. Dextran microspheres (Reviderm intra) induced a pronounced foreign body reaction and had disappeared at 6 months. Polymethylacrylate particles (Dermalive) induced the lowest cellular reaction but had disappeared clinically at 6 months. Polyacrylamide (Aquamid) was well tolerated and remained palpable to a lessening degree over the entire testing period. Histologically, it dissipated more slowly and was kept in place through fine fibrous capsules. Polyvinylhydroxide microspheres suspended in acrylamide (Evolution) were well tolerated, slowly diminishing over 9 months. Calcium hydroxylapatite microspheres (Radiance FN) induced almost no foreign body reaction but were absorbed by the skin at 12 months. Host defense mechanisms react differently to the various filler materials, but all substances-resorbable or nonresorbable-appeared to be clinically and histologically safe, although all exhibit undesirable side effects. Since the mechanism of late inflammation or

Dependence of injection locking of a TEA CO2 laser on intensity of injected radiation

NASA Technical Reports Server (NTRS)

Oppenheim, U. P.; Menzies, R. T.; Kavaya, M. J.

1982-01-01

The results of an experimental study to determine the minimum required injected power to control the output frequency of a TEA CO2 laser are reported. A CW CO2 waveguide laser was used as the injection oscillator. Both the power and the frequency of the injected radiation were varied, while the TEA resonator cavity length was adjusted to match the frequency of the injected signal. Single-longitudinal mode (SLM) TEA laser radiation was produced for injected power levels which are several orders of magnitude below those previously reported. The ratio of SLM output power to injection power exceeded 10 to the 12th at the lowest levels of injected intensity.

Unsteady boundary-layer injection

NASA Technical Reports Server (NTRS)

Telionis, D. P.; Jones, G. S.

1981-01-01

The boundary-layer equations for two-dimensional incompressible flow are integrated numerically for the flow over a flat plate and a Howarth body. Injection is introduced either impulsively or periodically along a narrow strip. Results indicate that injection perpendicular to the wall is transmitted instantly across the boundary layer and has little effect on the velocity profile parallel to the wall. The effect is a little more noticeable for flows with adverse pressure gradients. Injection parallel to the wall results in fuller velocity profiles. Parallel and oscillatory injection appears to influence the mean. The amplitude of oscillation decreases with distance from the injection strip but further downstream it increases again in a manner reminiscent of an unstable process.

Size-dependent lymphatic uptake of nanoscale-tailored particles as tumor mass increases.

PubMed

Kjellman, Pontus; Fredriksson, Sarah; Kjellman, Christian; Strand, Sven-Erik; Zandt, René In 't

2015-11-01

To investigate the size-dependent lymphatic uptake of nanoparticles in mice with rapidly growing syngeneic tumors. Mice were inoculated subcutaneously with EL4 lymphoma cells and on day 5 or day 6 of tumor growth, injected peritumorally with either 29 nm or 58 nm of ultra-small superparamagnetic iron oxide nanoparticles. Twenty-four hours later the animals were imaged using MRI. The larger of the two particles can only be detected in the lymph node when injected in animals with 6-day-old tumors while the 29 nm ultra-small superparamagnetic iron oxide nanoparticle is observed on both time points. Tumor mass greatly impacts the size of particles that are transported to the lymph nodes.

First injection of ketamine among young injection drug users (IDUs) in three U.S. cities

PubMed Central

Lankenau, Stephen E.; Sanders, Bill; Bloom, Jennifer Jackson; Hathazi, Dodi; Alarcon, Erica; Tortu, Stephanie; Clatts, Michael C.

2007-01-01

Ketamine, a dissociative anesthetic, has emerged as an increasingly common drug among subgroups of young injection drug users (IDUs) in cities across the United States. In-depth qualitative interviews were conducted with 213 young IDUs aged 16–28 years recruited in New York, New Orleans, and Los Angeles between 2004 and 2006. While some initiated injection drug use with ketamine, the drug was more frequently injected by IDUs with extensive polydrug using histories. IDUs initiating with ketamine commonly self-injected via an intramuscular mode of administration. The injection group provided crucial knowledge and material resources that enabled the injection event to occur, including ketamine, syringes, and injection skills. Injection paraphernalia was commonly shared during the first injection of ketamine, particularly vials of pharmaceutically-packaged liquid ketamine. Injection events infrequently occurred in a rave or club and more typically in a private home, which challenges ketamine’s designation as a ‘club’ drug. The first injection of ketamine was a noteworthy event since it introduced a novel drug or new mode of administration to be further explored by some, or exposed others to a drug to be avoided in the future. Risk reduction messages directed towards young IDUs should be expanded to include ketamine. PMID:16979848

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

78 FR 42776 - Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-17

... ENVIRONMENTAL PROTECTION AGENCY [FRL9834-8] Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection; Blanchard Refining... migration petition reissuance. SUMMARY: Notice is hereby given that a reissuance of an exemption to the land...

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.

Adaptive engine injection for emissions reduction

DOEpatents

Reitz, Rolf D. : Sun, Yong

2008-12-16

NOx and soot emissions from internal combustion engines, and in particular compression ignition (diesel) engines, are reduced by varying fuel injection timing, fuel injection pressure, and injected fuel volume between low and greater engine loads. At low loads, fuel is injected during one or more low-pressure injections occurring at low injection pressures between the start of the intake stroke and approximately 40 degrees before top dead center during the compression stroke. At higher loads, similar injections are used early in each combustion cycle, in addition to later injections which preferably occur between about 90 degrees before top dead center during the compression stroke, and about 90 degrees after top dead center during the expansion stroke (and which most preferably begin at or closely adjacent the end of the compression stroke). These later injections have higher injection pressure, and also lower injected fuel volume, than the earlier injections.

Physics of the current injection process during localized helicity injection

NASA Astrophysics Data System (ADS)

Hinson, Edward Thomas

An impedance model has been developed for the arc-plasma cathode electron current source used in localized helicity injection tokamak startup. According to this model, a potential double layer (DL) is established between the high-density arc plasma (narc ˜ 1021 m-3) in the electron source, and the less-dense external tokamak edge plasma (nedge ˜ 10 18 m-3) into which current is injected. The DL launches an electron beam at the applied voltage with cross-sectional area close to that of the source aperture: Ainj ≈ 2 cm 2. The injected current, Iinj, increases with applied voltage, Vinj, according to the standard DL scaling, Iinj ˜ V(3/2/ inj), until the more restrictive of two limits to beam density nb arises, producing Iinj ˜ V(1/2/inj), a scaling with beam drift velocity. For low external tokamak edge density nedge, space-charge neutralization of the intense electron beam restricts the injected beam density to nb ˜ nedge. At high Jinj and sufficient edge density, the injected current is limited by expansion of the DL sheath, which leads to nb ˜ narc. Measurements of narc, Iinj , nedge, Vinj, support these predicted scalings, and suggest narc as a viable control actuator for the source impedance. Magnetic probe signals ≈ 300 degrees toroidally from the injection location are consistent with expectations for a gyrating, coherent electron beam with a compact areal cross-section. Technological development of the source has allowed an extension of the favorable Iinj ˜ V(1/2/inj) to higher power without electrical breakdown.

Parametric study of injection rates with solenoid injectors in an injection quantity and rate measuring device

DOE PAGES

Busch, Stephen; Miles, Paul C.

2015-03-31

A Moehwald HDA (HDA is a German acronym: Hydraulischer Druckanstieg: hydraulic pressure increase) injection quantity and rate measuring unit is used to investigate injection rates obtained with a fast-acting, preproduction diesel solenoid injector. Experimental parametric variations are performed to determine their impact on measured injection rate traces. A pilot–main injection strategy is investigated for various dwell times; these preproduction injectors can operate with very short dwell times with distinct pilot and main injection events. Dwell influences the main injection rate shape. Furthermore, a comparison between a diesel-like fuel and a gasoline-like fuel shows that injection rates are comparable for amore » single injection but dramatically different for multiple injections with short dwells.« less

75 FR 60457 - Underground Injection Control Program Hazardous Waste Injection Restrictions; Petition for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9208-4] Underground Injection Control Program Hazardous Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection Dow Chemical Company (DOW... Petition. SUMMARY: Notice is hereby given that an exemption to the land disposal restrictions under the...

Brentuximab Vedotin Injection

MedlinePlus

... with healthy bone marrow) or at least two treatment periods of chemotherapy. Brentuximab vedotin injection is also ... Hodgkin lymphoma) who did not respond to another treatment period of chemotherapy. Brentuximab vedotin injection is in ...

Parathyroid Hormone Injection

MedlinePlus

... injection is used along with calcium and vitamin D to treat low levels of calcium in the ... condition can be controlled by calcium and vitamin D alone. Parathyroid hormone injection is in a class ...

Investigation of a cutaneous delayed hypersensitivity response as a means of detecting Salmonella dublin infection in cattle.

PubMed

Aitken, M M; Hall, G A; Jones, P W

1978-05-01

Delayed hypersensitivity reactions developed 48 to 96 h after intradermal injection of killed Salmonella dublin in 25 of 28 cattle which had been inoculated intravenously, and in five of 10 cattle which had been inoculated orally with S dublin 24 to 493 days previously. Control animals showed no delayed hypersensitivity reactions. Persistence of infection in five of the intravenously inoculated and in four of the orally inoculated animals was confirmed by isolation of S dublin from the carcases at necropsy one week after skin testing. Failure to isolate the organism from the carcases of 21 animals which had reacted positively to the intradermal test did not eliminate the possibility of their being carriers of S dublin. Skin testing was concluded to be a reliable means of identifying animals which had been, and possibly still were, infected systemically with S dublin. However recovered animals might be falsely identified as infected. Repeated testing gave misleading results.

Immunotherapy using regulatory T cells in cancer suggests more flavors of hypersensitivity type IV.

PubMed

Pakravan, Nafiseh; Hassan, Zuhair Mohammad

2018-03-01

Regulatory T cells (Tregs) profoundly affect tumor microenvironment and exert dominant suppression over antitumor immunity in response to self-antigen expressed by tumor. Immunotherapy targeting Tregs lead to a significant improvement in antitumor immunity. Intradermal injection of tumor antigen results in negative delayed-type hypersensitivity (DTH) type IV. However, anti-Tregs treatment/use of adjuvant along with tumor antigens turns DTH to positive. Considering Tregs as the earliest tumor sensor/responders, tumor can be regarded as Treg-mediated type IV hypersensitivity and negative DTH to tumor antigen is due to anti-inflammatory action of Tregs to tumor antigens at the injection site. Such a view would help us in basic and clinical situations to testify a candidate vaccine via dermal administration and evaluation of Treg proportion at injection site.

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 ...

76 FR 55908 - Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... of an exemption to the land disposal restrictions, under the 1984 Hazardous and Solid Waste... Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection; Great Lakes... from the injection zone for as long as the waste remains hazardous. This final decision allows the...

78 FR 23246 - Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... exemption to the land disposal Restrictions, under the 1984 Hazardous and Solid Waste [[Page 23247... Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection; BASF... from the injection zone for as long as the waste remains hazardous. This final decision allows the...

77 FR 26755 - Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-07

... reissuance of an exemption to the land disposal Restrictions, under the 1984 Hazardous and Solid Waste... Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection; Diamond... from the injection zone for as long as the waste remains hazardous. This final decision allows the...

Corticotropin, Repository Injection

MedlinePlus

Corticotropin repository injection is used to treat the following conditions:infantile spasms (seizures that usually begin during the first ... of the arms, hands, feet, and legs). Corticotropin repository injection is in a class of medications called ...

Epoetin Alfa Injection

MedlinePlus

Epoetin alfa injection is used to treat anemia (a lower than normal number of red blood cells) in people ... stop working over a period of time). Epoetin alfa injection is also used to treat anemia caused ...

Darbepoetin Alfa Injection

MedlinePlus

Darbepoetin alfa injection is used to treat anemia (a lower than normal number of red blood cells) in people ... stop working over a period of time). Darbepoetin alfa injection is also used to treat anemia caused ...

Iron Dextran Injection

MedlinePlus

Iron dextran injection is used to treat iron-deficiency anemia (a lower than normal number of red blood cells ... treated with iron supplements taken by mouth. Iron dextran injection is in a class of medications called ...

Surgical versus injection treatment for injection-confirmed chronic sacroiliac joint pain

PubMed Central

Spiker, William Ryan; Lawrence, Brandon D.; Raich, Annie L.; Skelly, Andrea C.; Brodke, Darrel S.

2012-01-01

Study design: Systematic review. Study rationale: Chronic sacroiliac joint pain (CSJP) is a common clinical entity with highly controversial treatment options. A recent systematic review compared surgery with denervation, but the current systematic review compares outcomes of surgical intervention with therapeutic injection for the treatment of CSJP and serves as the next step for evaluating current evidence on the comparative effectiveness of treatments for non-traumatic sacroiliac joint pain. Objective or clinical question: In adult patients with injection-confirmed CSJP, does surgical treatment lead to better outcomes and fewer complications than injection therapy? Methods: A systematic review of the English-language literature was undertaken for articles published between 1970 and June 2012. Electronic databases and reference lists of key articles were searched to identify studies evaluating surgery or injection treatment for injection-confirmed CSJP. Studies involving traumatic onset or non-injection–confirmed CSJP were excluded. Two independent reviewers assessed the level of evidence quality using the grading of recommendations assessment, development and evaluation (GRADE) system, and disagreements were resolved by consensus. Results: We identified twelve articles (seven surgical and five injection treatment) meeting our inclusion criteria. Regardless of the type of treatment, most studies reported over 40% improvement in pain as measured by Visual Analog Scale or Numeric rating Scale score. Regardless of the type of treatment, most studies reported over 20% improvement in functionality. Most complications were reported in the surgical studies. Conclusion: Surgical fusion and therapeutic injections can likely provide pain relief, improve quality of life, and improve work status. The comparative effectiveness of these interventions cannot be evaluated with the current literature. PMID:23526911

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.

Repeated onabotulinumtoxin-a injections provide better results than single injection in treatment of painful bladder syndrome.

PubMed

Kuo, Hann-Chorng

2013-01-01

Onabotulinumtoxin-A (BoNT-A) is effective for the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS). However, long-term follow-up does not show successful outcome after a single injection. To evaluate the efficacy and safety of repeated intravesical BoNT-A injections for treatment of IC/PBS and compare the success rates among patient groups receiving different injection numbers. Prospective interventional study. Tertiary medical center. Intravesical injection of 100 U of BoNT-A was performed in 81 patients every 6 months for up to 4 times or until patients' symptoms significantly improved. Patients who received a single injection served as active controls. Measured parameters included O'Leary-Sant symptom indexes (ICSI) and problem indexes (ICPI), visual analogue score (VAS) for pain, voiding diary variables, urodynamic parameters, maximal bladder capacity under anesthesia, glomerulation grade, and global response assessment. Multiple measurements and Kaplan-Meier analysis were used for comparison of consecutive data and success rates among groups. Among 81 patients, 20 received single injections, 19 received 2 injections, 12 received 3 injections, and 30 received 4 injections. The mean (± standard deviation) of ICSI, ICPI, total scores, VAS, functional bladder capacity, and daytime frequency all showed significant improvement after repeated BoNT-A treatment with different injections. Significantly better success rates were noted in patients who received 4 repeated injections (P = 0.0242) and 3 injections (P = 0.050), compared to those who received a single injection. However, there was no significant difference of long-term success rates among patients who received 2, 3, and 4 injections. Lack of placebo control group is the main limitation. Repeated intravesical BoNT-A injections were safe and effective for pain relief and they increased bladder capacity and provided a better long-term success rate than a single injection did for treatment of

Transitions from injecting to non-injecting drug use: potential protection against HCV infection

PubMed Central

Des Jarlais, Don C.; McKnight, Courtney; Arasteh, Kamyar; Feelemyer, Jonathan; Perlman, David C.; Hagan, Holly; Cooper, Hannah L. F.

2013-01-01

Transitions from injecting to non-injecting drug use have been reported from many different areas, particularly in areas with large human immunodeficiency virus (HIV) epidemics. The extent to which such transitions actually protect against HIV and HCV has not been determined. A cross-sectional survey with HIV and hepatitis C (HCV) testing was conducted with 322 former injectors (persons who had injected illicit drugs but permanently transitioned to non-injecting use) and 801 current injectors recruited in New York City between 2007 and 2012. There were no differences in HIV prevalence, while HCV prevalence was significantly lower among former injectors compared to current injectors. Years injecting functioned as a mediating variable linking former injector status to lower HCV prevalence. Transitions have continued well beyond the reduction in the threat of AIDS to injectors in the city. New interventions to support transitions to non-injecting drug use should be developed and supported by both drug treatment and syringe exchange programs. PMID:24161262

Methodology for the Randomised Injecting Opioid Treatment Trial (RIOTT): evaluating injectable methadone and injectable heroin treatment versus optimised oral methadone treatment in the UK

PubMed Central

Lintzeris, Nicholas; Strang, John; Metrebian, Nicola; Byford, Sarah; Hallam, Christopher; Lee, Sally; Zador, Deborah

2006-01-01

Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding the safety, efficacy and cost effectiveness of this treatment approach remains equivocal. Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high-quality oral methadone treatment who continue to regularly inject heroin, and that treatment be initiated in newly-developed supervised injecting clinics. The Randomised Injectable Opioid Treatment Trial (RIOTT) is a multisite, prospective open-label randomised controlled trial (RCT) examining the role of treatment with injected opioids (methadone and heroin) for the management of heroin dependence in patients not responding to conventional substitution treatment. Specifically, the study examines whether efforts should be made to optimise methadone treatment for such patients (e.g. regular attendance, supervised dosing, high oral doses, access to psychosocial services), or whether such patients should be treated with injected methadone or heroin. Eligible patients (in oral substitution treatment and injecting illicit heroin on a regular basis) are randomised to one of three conditions: (1) optimized oral methadone treatment (Control group); (2) injected methadone treatment; or (3) injected heroin treatment (with access to oral methadone doses). Subjects are followed up for 6-months, with between-group comparisons on an intention-to-treat basis across a range of outcome measures. The primary outcome is the proportion of patients who discontinue regular illicit heroin use (operationalised as providing >50% urine drug screens negative for markers of

Syringe injectable electronics

PubMed Central

Hong, Guosong; Zhou, Tao; Jin, Lihua; Duvvuri, Madhavi; Jiang, Zhe; Kruskal, Peter; Xie, Chong; Suo, Zhigang; Fang, Ying; Lieber, Charles M.

2015-01-01

Seamless and minimally-invasive three-dimensional (3D) interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating syringe injection and subsequent unfolding of submicrometer-thick, centimeter-scale macroporous mesh electronics through needles with a diameter as small as 100 micrometers. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with > 90% device yield. We demonstrate several applications of syringe injectable electronics as a general approach for interpenetrating flexible electronics with 3D structures, including (i) monitoring of internal mechanical strains in polymer cavities, (ii) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (iii) in vivo multiplexed neural recording. Moreover, syringe injection enables delivery of flexible electronics through a rigid shell, delivery of large volume flexible electronics that can fill internal cavities and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics. PMID:26053995

Endoscopic injection therapy.

PubMed

Kim, Sang Woon; Lee, Yong Seung; Han, Sang Won

2017-06-01

Since the U.S. Food and Drug Administration approved dextranomer/hyaluronic acid copolymer (Deflux) for the treatment of vesicoureteral reflux, endoscopic injection therapy using Deflux has become a popular alternative to open surgery and continuous antibiotic prophylaxis. Endoscopic correction with Deflux is minimally invasive, well tolerated, and provides cure rates approaching those of open surgery (i.e., approximately 80% in several studies). However, in recent years a less stringent approach to evaluating urinary tract infections (UTIs) and concerns about long-term efficacy and complications associated with endoscopic injection have limited the use of this therapy. In addition, there is little evidence supporting the efficacy of endoscopic injection therapy in preventing UTIs and vesicoureteral reflux-related renal scarring. In this report, we reviewed the current literature regarding endoscopic injection therapy and provided an updated overview of this topic.

Extraforaminal needle tip position reduces risk of intravascular injection in CT-fluoroscopic lumbar transforaminal epidural steroid injections

PubMed Central

Yu, Robinson K.; Ghodadra, Anish; Agarwal, Vikas

2016-01-01

Background Lumbar transforaminal epidural steroid injection is a common and effective tool for managing lumbar radicular pain, although accidental intravascular injection can rarely result in paralysis. The purpose of this study is to determine the safest needle tip position for computed tomography (CT)-guided lumbar transforaminal epidural steroid injections as determined by incidence of intravascular injection. Methods Three radiologists, in consensus, reviewed procedural imaging for consecutive CT-fluoroscopic lumbar transforaminal epidural steroid injections performed during a 16-month period. Intravascular injections were identified and categorized by needle tip position, vessel type injected, intravascular injection volume and procedural phase containing the intravascular injection. Pearson chi-square and logistic regression testing were used to assess differences between groups, as appropriate. Results Intravascular injections occurred in 9% (52/606) of injections. The intravascular injection rate was significantly lower (P<0.001) for extraforaminal needle position (0%, 0/109) compared to junctional (8%, 27/319) and foraminal (14%, 25/178) needle tip positions. Of the intravascular injections, 4% (2/52) were likely arterial, 35% (18/52) were likely venous, and 62% (32/52) were indeterminate for vessel type injected. 46% (24/52) of intravascular injections were large volume, 33% (17/52) were small volume, and 21% (11/52) were trace volume. 56% (29/52) of intravascular injections occurred with the contrast trial dose, 29% (15/52) with the steroid/analgesic cocktail, and 15% (8/52) with both. Conclusions An extraforaminal needle position for CT-fluoroscopic lumbar transforaminal epidural steroid injections decreases the risk of intravascular injection and therefore may be safer than other needle tip positions. PMID:28097241

Deformational injection rate measuring method

NASA Astrophysics Data System (ADS)

Marčič, Milan

2002-09-01

After completing the diesel engine endurance testing, we detected various traces of thermal load on the walls of combustion chambers located in the engine pistons. The engines were fitted with ω combustion chambers. The thermal load of different intensity levels occurred where the spray of fuel, fuel vapor, and air interacted with the combustion chamber wall. The uneven thermal load distribution of the combustion chamber wall results from varying injection rates in each injection nozzle hole. The most widely applied controlling methods so far for injection rate measurement, such as the Zeuch and Bosch concepts, allow measurement of only the total injection rate in multihole nozzles, without providing any indication whatsoever of the injection rate differences in individual injection nozzle holes. The new deformational measuring method described in the article allows the injection rate to be measured in each hole of the multihole nozzle. The results of the measurements using this method showed that the differences occurred in injection rates of individual injection nozzle holes. These differences may be the cause of various thermal loads on the combustion chamber walls. The criterion for injection rate is the deformation of the membrane due to an increase in the fuel quantity in the measuring space and due to the pressure waves resulting from the fuel being injected into the measuring space. The membrane deformation is measured using strain gauges, glued to the membrane and forming the Wheatstone's bridge. We devoted special attention to the temperature compensation of the Wheatstone's bridge and the membrane, heated up during the measurements.

Appraisal of interpretation criteria for the single intra-dermal comparative cervical tuberculin test for the diagnosis of tuberculosis in dromedary camels in Ethiopia.

PubMed

Jibril, Yasmin; Mamo, Gezahegne; Issa, Ahmed; Zewude, Aboma; Ameni, Gobena

2018-05-02

Dromedary camels are the main sources of milk, meat and income for the Ethiopian pastoralists as they withstand the harsh environments of the regions of the country. Tuberculosis (TB) affects dromedary camels causing morbidity and mortality in these animals. Hence, early diagnosis and identification of infected camels play a significant role in reducing the transmission of TB in camels. This study was conducted on 168 camels between October 2014 and July 2015 to evaluate the performance of single intra-dermal comparative cervical tuberculin (SICCT) to diagnose TB in camels. Gross pathology was used as a gold standard to define disease status of each camel. The result showed that at the cutoff value of ≥ 3 mm SICCT had optimum performance with sensitivity and specificity of 60.7 and 85%, respectively. Moreover, at a cutoff ≥ 3 mm, the receiver operating characteristics (ROC) revealed area under the ROC curve was 0.729 (0.615-0.842) which is statistically significant (p = 0.000). Thus, the result of the present study could suggest the use of ≥ 3 mm cutoff value for the diagnosis of TB in dromedary camels in Ethiopia.

PSR Injection Line Upgrade

NASA Astrophysics Data System (ADS)

Blind, Barbara; Jason, Andrew J.

1997-05-01

We describe the new injection line to be implemented for the Los Alamos Proton Storage Ring in the change from a two-step process to direct H- injection. While obeying all geometrical constraints imposed by the existing structures, the new line has properties not found in the present injection line. In particular, it features decoupled transverse phase spaces downstream of the skew bend and a high degree of tunability of the beam at the injection foil. A comprehensive set of error studies has dictated the component tolerances imposed and has indicated the expected performance of the system.

Evaluation of a DNA Aβ42 vaccine in adult rhesus monkeys (Macaca mulatta): antibody kinetics and immune profile after intradermal immunization with full-length DNA Aβ42 trimer.

PubMed

Lambracht-Washington, Doris; Fu, Min; Frost, Pat; Rosenberg, Roger N

2017-04-26

Aggregated amyloid-β peptide 1-42 (Aβ42), derived from the cellular amyloid precursor protein, is one of the pathological hallmarks of Alzheimer's disease (AD). Although active immunization against Aβ42 peptide was successful in AD mouse models and led to removal of plaques and improved memory, a similar clinical trial in humans (Aβ42 peptide immunization with QS-21 adjuvant) was stopped in phase II, when 6% of the treated patients developed encephalitis. Currently ongoing passive immunizations with the injection of preformed monoclonal antibodies against different epitopes within the Aβ 1-42 peptide, which do not lead to activation of the immune system, have shown some effects in slowing AD pathology. Active DNA Aβ42 immunizations administered with the gene gun into the skin are noninflammatory because they activate a different T-cell population (Th2) with different cytokine responses eliciting a different humoral immune response. We present our findings in rhesus macaques that underwent the DNA Aβ42 immunization via gene gun delivery into the skin. Six rhesus monkeys received two different doses of a DNA Aβ42 trimer vaccine. The humoral immune response was analyzed from blood throughout the study, and cellular immune responses were determined in peripheral blood mononuclear cells (PBMCs) after three and six immunizations. DNA Aβ42 trimer immunization led to high titer antibody responses in the nonhuman primate (NHP) model. Antibodies generated in the rhesus monkeys following DNA Aβ42 immunization detected amyloid plaques consisting of human Aβ42 peptide in the brain of the triple-transgenic AD mouse model. T-cell responses showed no interferon (IFN)-γ- and interleukin (IL)-17-producing cells from PBMCs in Enzyme-Linked ImmunoSpot assays after three immunization time points. At six immunization time points, IFN-γ- and IL-17-producing cells were found in immunized animals as well as in control animals and were thus considered nonspecific and not due to

Ducted fuel injection: A new approach for lowering soot emissions from direct-injection engines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Charles J.; Nilsen, Christopher W.; Ruth, Daniel J.

Designers of direct-injection compression-ignition engines use a variety of strategies to improve the fuel/charge-gas mixture within the combustion chamber for increased efficiency and reduced pollutant emissions. Strategies include the use of high fuel-injection pressures, multiple injections, small injector orifices, flow swirl, long-ignition-delay conditions, and oxygenated fuels. This is the first journal publication paper on a new mixing-enhancement strategy for emissions reduction: ducted fuel injection. The concept involves injecting fuel along the axis of a small cylindrical duct within the combustion chamber, to enhance the mixture in the autoignition zone relative to a conventional free-spray configuration (i.e., a fuel spray thatmore » is not surrounded by a duct). Finally, the results described herein, from initial proof-of-concept experiments conducted in a constant-volume combustion vessel, show dramatically lower soot incandescence from ducted fuel injection than from free sprays over a range of charge-gas conditions that are representative of those in modern direct-injection compression-ignition engines.« less

Ducted fuel injection: A new approach for lowering soot emissions from direct-injection engines

DOE PAGES

Mueller, Charles J.; Nilsen, Christopher W.; Ruth, Daniel J.; ...

2017-07-18

Designers of direct-injection compression-ignition engines use a variety of strategies to improve the fuel/charge-gas mixture within the combustion chamber for increased efficiency and reduced pollutant emissions. Strategies include the use of high fuel-injection pressures, multiple injections, small injector orifices, flow swirl, long-ignition-delay conditions, and oxygenated fuels. This is the first journal publication paper on a new mixing-enhancement strategy for emissions reduction: ducted fuel injection. The concept involves injecting fuel along the axis of a small cylindrical duct within the combustion chamber, to enhance the mixture in the autoignition zone relative to a conventional free-spray configuration (i.e., a fuel spray thatmore » is not surrounded by a duct). Finally, the results described herein, from initial proof-of-concept experiments conducted in a constant-volume combustion vessel, show dramatically lower soot incandescence from ducted fuel injection than from free sprays over a range of charge-gas conditions that are representative of those in modern direct-injection compression-ignition engines.« less

Sensor for Injection Rate Measurements

PubMed Central

Marcic, Milan

2006-01-01

A vast majority of the medium and high speed Diesel engines are equipped with multi-hole injection nozzles nowadays. Inaccuracies in workmanship and changing hydraulic conditions in the nozzles result in differences in injection rates between individual injection nozzle holes. The new deformational measuring method described in the paper allows injection rate measurement in each injection nozzle hole. The differences in injection rates lead to uneven thermal loads of Diesel engine combustion chambers. All today known measuring method, such as Bosch and Zeuch give accurate results of the injection rate in diesel single-hole nozzles. With multihole nozzles they tell us nothing about possible differences in injection rates between individual holes of the nozzle. At deformational measuring method, the criterion of the injected fuel is expressed by the deformation of membrane occurring due to the collision of the pressure wave against the membrane. The pressure wave is generated by the injection of the fuel into the measuring space. For each hole of the nozzle the measuring device must have a measuring space of its own into which fuel is injected as well as its measuring membrane and its own fuel outlet. During measurements procedure the measuring space must be filled with fuel to maintain an overpressure of 5 kPa. Fuel escaping from the measuring device is conducted into the graduated cylinders for measuring the volumetric flow through each hole of the nozzle.The membrane deformation is assessed by strain gauges. They are glued to the membrane and forming the full Wheatstone's bridge. We devoted special attention to the membrane shape and temperature compensation of the strain gauges.

2.4-3.2 GHz robust self-injecting injection-locked phase-locked loop

NASA Astrophysics Data System (ADS)

Yang, Jincheng; Zhang, Zhao; Qi, Nan; Liu, Liyuan; Liu, Jian; Wu, Nanjian

2018-04-01

In this paper, we propose a robust self-injecting injection-locked phase-locked loop (SI-ILPLL). It adopts a phase alignment loop (PAL) based on a subsampling phase frequency detector to align the phase between the injected pulse and the voltage-controlled oscillator (VCO) output. With the proposed phase frequency detector, the PAL performs phase alignment and the pulse generator can self-inject pulses into the VCO for injection locking. The subsampling phase detection and self-injection locking techniques can suppress the phase noise of the SI-ILPLL. The SI-ILPLL shows excellent robustness to environmental interference. The SI-ILPLL is implemented in 65 nm CMOS technology. It occupies an active area of 0.7 mm2. The measured root-mean-square (RMS) jitters at 3.2 GHz output without and with injection locking are 216 and 131 fs, respectively. When the supply voltage varies from 1.17 to 1.23 V and the temperature varies from 0 to 80 °C, the maximum jitter variation of all the output frequencies is less than 50 fs. The measured results demonstrate that even when a large interference appears at the supply voltage and unlocks the SI-ILPLL, the SI-ILPLL can self-recover its injection-locked state rapidly after the disturbance disappears, whereas the conventional ILPLL cannot self-recover its locked state after losing it. The power consumption of the SI-ILPLL is 7.4 mW under a 1.2 V supply voltage. The SI-ILPLL achieves a figure of merit (FOM) of -249 dB.

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.

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

Syringe-injectable electronics.

PubMed

Liu, Jia; Fu, Tian-Ming; Cheng, Zengguang; Hong, Guosong; Zhou, Tao; Jin, Lihua; Duvvuri, Madhavi; Jiang, Zhe; Kruskal, Peter; Xie, Chong; Suo, Zhigang; Fang, Ying; Lieber, Charles M

2015-07-01

Seamless and minimally invasive three-dimensional interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating the syringe injection (and subsequent unfolding) of sub-micrometre-thick, centimetre-scale macroporous mesh electronics through needles with a diameter as small as 100 μm. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with >90% device yield. We demonstrate several applications of syringe-injectable electronics as a general approach for interpenetrating flexible electronics with three-dimensional structures, including (1) monitoring internal mechanical strains in polymer cavities, (2) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (3) in vivo multiplexed neural recording. Moreover, syringe injection enables the delivery of flexible electronics through a rigid shell, the delivery of large-volume flexible electronics that can fill internal cavities, and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics.

Syringe-injectable electronics

NASA Astrophysics Data System (ADS)

Liu, Jia; Fu, Tian-Ming; Cheng, Zengguang; Hong, Guosong; Zhou, Tao; Jin, Lihua; Duvvuri, Madhavi; Jiang, Zhe; Kruskal, Peter; Xie, Chong; Suo, Zhigang; Fang, Ying; Lieber, Charles M.

2015-07-01

Seamless and minimally invasive three-dimensional interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating the syringe injection (and subsequent unfolding) of sub-micrometre-thick, centimetre-scale macroporous mesh electronics through needles with a diameter as small as 100 μm. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with >90% device yield. We demonstrate several applications of syringe-injectable electronics as a general approach for interpenetrating flexible electronics with three-dimensional structures, including (1) monitoring internal mechanical strains in polymer cavities, (2) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (3) in vivo multiplexed neural recording. Moreover, syringe injection enables the delivery of flexible electronics through a rigid shell, the delivery of large-volume flexible electronics that can fill internal cavities, and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics.

Comparison of incidence of intravascular injections during transforaminal epidural steroid injection using different needle types

PubMed Central

Lee, Yong Ho

2014-01-01

Background Infrequent but serious complications of transforaminal epidural steroid injection (TFESI) occur due to inadvertent intravascular injections. A few studies reported that the different needle types can influence on the occurrences of intravascular incidence in TFESI. This study prospectively evaluated whether short-bevel needle can reduce the incidences of intravascular injection of TFESI compared to long-bevel needles. Methods From March 2013 to December 2013, 239 consecutive patients were enrolled and received 249 fluoroscopically guided TFESI using the classic technique. Confirmation of intravascular spread was done initially with real time fluoroscopy and then with digital subtraction angiography method in a same patient. Injection technique for TFESI was the same for both short-bevel and long-bevel needle types. Results The incidences of intravascular injections with the long-bevel and short-bevel needles were 15.0% (21/140) and 9.2% (4/140), respectively. More than half of intravascular injections occurred simultaneously with epidural injections (8.0%, 20/249). There were no statistically significant differences between the long-bevel and the short-bevel needles in the rates of intravascular injections (P = 0.17). Conclusions Short-bevel needles did not demonstrate any benefits in reducing the incidence of intravascular injection. PMID:25302096

Hydrogeology and results of injection tests at waste-injection test sites in Pinellas County, Florida

USGS Publications Warehouse

Hickey, John J.

1982-01-01

Potential benefits or hazards to freshwater resources could result from subsurface injection of treated wastewater. Recognizing this, the U.S. Geological Survey, in cooperation with Pinellas County and the city of St. Petersburg, undertook an evaluation of the hydrogeology and injection of wastewater at proposed test sites on the Pinellas peninsula. The injection sites are underlain by sedimentary rocks ranging in age from Cretaceous to Pleistocene. Lower Eocene carbonate rocks were penetrated to a maximum depth of 3,504 feet and were found to have relatively low water yields. The most permeable part of the investigated section was in rocks of middle Eocene age within the Floridan aquifer. At the injection sites, the Floridan aquifer was subdivided into four permeable zones and three semiconfining beds. The test injection zone is within the Avon Park Limestone, the most productive of the identified permeable zones, with a transmissivity of about 1,000,000 feet squared per day. Two semiconfining beds are above the injection zone in the Suwannee Limestone and Ocala Limestone and have vertical hydraulic conductivities estimated to range from about 0.1 to 1 foot per day where these beds do not contain clay. Limited fresh ground-water supplies exist in the Floridan aquifer within the Pinellas peninsula. At all test sites, chloride concentration in the injection zone ranged from 19,000 to 20,000 milligrams per liter. Injection tests ranging in duration from 3 to 91.1 days were run at three different sites. Pressure buildup occurred in permeable zones above and below the injection zone during these tests. Calculated pressure buildup in observation wells close to and at some distance from the test wells was typically less than 1 pound per square inch. Injection and formation water will probably move slowly through the semiconfining bed overlying the injection zone, and long-term injection tests will be needed to determine the effectiveness of these beds to retard flow. The

Comparison between sensitivity of autologous skin serum test and autologous plasma skin test in patients with Chronic Idiopathic Urticaria for detection of antibody against IgE or IgE receptor (FcεRIα).

PubMed

Sajedi, Vahid; Movahedi, Masoud; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Gharagozlou, Mohammad; Ghareguzlou, Mohammad; Shafiei, Alireza; Soheili, Habib; Sanajian, Nahal

2011-06-01

Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria (CIU). This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma (anticoagulated by citrate). Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests (CBC, U/A etc), allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed.There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant.Autologus serum skin test (ASST) and autologous plasma skin test (APST) could be used for estimation of duration and severity of urticaria and planning for the treatment.

Fluorescence fibre-optic confocal microscopy of skin in vivo: microscope and fluorophores.

PubMed

Suihko, Christian; Swindle, Lucinda D; Thomas, Steven G; Serup, Jørgen

2005-11-01

Fibre-optic confocal imaging in vivo is a new approach in the assessment of human skin. The objective is to describe a novel instrument and its operation and use in combination with fluorophores. The Stratum is a fibre-optic fluorescence confocal microscope especially developed for the study of skin and mucous membranes. The system is flexible and any body site can be studied with a hand-held scanner. The light source is a 488 nm argon ion laser. Horizontal (en face) images of the epidermis and outer dermis are produced with cellular resolution. Magnification is approximately 1000 x . Fluorescein sodium is routinely used as fluorophore (intradermal injection or application to the skin surface). This fluorophore is safe for human use in vivo, but other substances (rhodamine B, Acridine Orange, green fluorescent protein, curcumin) have also been studied. The instrument produces sharp images of epidermal cell layers from the epidermal surface to the sub-papillary dermis, with sub-cellular resolution. The scanner is flexible in use. The technique of intradermal fluorophore injection requires some skill. We consider this fibre-optic instrument a potentially important tool in skin research for non-invasive optical biopsy of primarily the epidermis. Present use is focussed on research applications, where the fluorophore distribution in the skin may illustrate morphological changes in the epidermis.

AbobotulinumtoxinA Injection

MedlinePlus

... tightening of the neck muscles that may cause neck pain and abnormal head positions). AbobotulinumtoxinA injection is also ... it. If you are using abobotulinumtoxinA to treat cervical dystonia, it may take 2 weeks or longer before you feel the full benefit of abobotulinumtoxinA injection.

Reduced injection pressures using a compressed air injection technique (CAIT): an in vitro study.

PubMed

Tsui, Ban C H; Knezevich, Mark P; Pillay, Jennifer J

2008-01-01

High injection pressures have been associated with intraneural injection and persistent neurological injury in animals. Our objective was to test whether a reported simple compressed air injection technique (CAIT) would limit the generation of injection pressures to below a suggested 1,034 mm Hg limit in an in vitro model. After ethics board approval, 30 consenting anesthesiologists injected saline into a semiclosed system. Injection pressures using 30 mL syringes connected to a 22 gauge needle and containing 20 mL of saline were measured for 60 seconds using: (1) a typical "syringe feel" method, and (2) CAIT, thereby drawing 10 mL of air above the saline and compressing this to 5 mL prior to and during injections. All anesthesiologists performed the syringe feel method before introduction and demonstration of CAIT. Using CAIT, no anesthesiologist generated pressures above 1,034 mm Hg, while 29 of 30 produced pressures above this limit at some time using the syringe feel method. The mean pressure using CAIT was lower (636 +/- 71 vs. 1378 +/- 194 mm Hg, P = .025), and the syringe feel method resulted in higher peak pressures (1,875 +/- 206 vs. 715 +/- 104 mm Hg, P = .000). This study demonstrated that CAIT can effectively keep injection pressures under 1,034 mm Hg in this in vitro model. Animal and clinical studies will be needed to determine whether CAIT will allow objective, real-time pressure monitoring. If high pressure injections are proven to contribute to nerve injury in humans, this technique may have the potential to improve the safety of peripheral nerve blocks.

Pellet injection technology

NASA Astrophysics Data System (ADS)

Combs, S. K.

1993-07-01

During the last 10 to 15 years, significant progress has been made worldwide in the area of pellet injection technology. This specialized field of research originated as a possible solution to the problem of depositing atoms of fuel deep within magnetically confined, hot plasmas for refueling of fusion power reactors. Using pellet injection systems, frozen macroscopic (millimeter-size) pellets composed of the isotopes of hydrogen are formed, accelerated, and transported to the plasma for fueling. The process and benefits of plasma fueling by this approach have been demonstrated conclusively on a number of toroidal magnetic confinement configurations; consequently, pellet injection is the leading technology for deep fueling of magnetically confined plasmas for controlled thermonuclear fusion research. Hydrogen pellet injection devices operate at very low temperatures (≂10 K) at which solid hydrogen ice can be formed and sustained. Most injectors use conventional pneumatic (light gas gun) or centrifuge (mechanical) acceleration concepts to inject hydrogen or deuterium pellets at speeds of ≂1-2 km/s. Pellet injectors that can operate at quasi-steady state (pellet delivery rates of 1-40 Hz) have been developed for long-pulse fueling. The design and operation of injectors with the heaviest hydrogen isotope, tritium, offer some special problems because of tritium's radioactivity. To address these problems, a proof-of-principle experiment was carried out in which tritium pellets were formed and accelerated to speeds of 1.4 km/s. Tritium pellet injection is scheduled on major fusion research devices within the next few years. Several advanced accelerator concepts are under development to increase the pellet velocity. One of these is the two-stage light gas gun, for which speeds of slightly over 4 km/s have already been reported in laboratory experiments with deuterium ice. A few two-stage pneumatic systems (single-shot) have recently been installed on tokamak

Prevalence and correlates of crack-cocaine injection among young injection drug users in the United States, 1997-1999.

PubMed

Santibanez, Scott S; Garfein, Richard S; Swartzendruber, Andrea; Kerndt, Peter R; Morse, Edward; Ompad, Danielle; Strathdee, Steffanie; Williams, Ian T; Friedman, Samuel R; Ouellet, Lawrence J

2005-03-07

We estimated prevalence and identified correlates of crack-cocaine injection among young injection drug users in the United States. We analyzed data from the second Collaborative Injection Drug Users Study (CIDUS II), a 1997-1999 cohort study of 18-30-year-old, street-recruited injection drug users from six US cities. Crack-cocaine injection was reported by 329 (15%) of 2198 participants. Prevalence varied considerably by site (range, 1.5-28.0%). No participants injected only crack-cocaine. At four sites where crack-cocaine injection prevalence was greater than 10%, recent (past 6 months) crack-cocaine injection was correlated with recent daily injection and sharing of syringes, equipment, and drug solution. Lifetime crack-cocaine injection was correlated with using shooting galleries, initiating others into drug injection, and having serologic evidence of hepatitis B virus and hepatitis C virus infection. Crack-cocaine injection may be a marker for high-risk behaviors that can be used to direct efforts to prevent HIV and other blood-borne viral infections.

Phorbol 12-myristate 13-acetate enhances nm23 gene expression in murine melanocytes but not in syngeneic B16-BL6 melanoma variants.

PubMed

Huijzer, J C; McFarland, M; Niles, R M; Meadows, G G

1996-03-01

The nm23 gene has been described as a potential metastasis suppressor gene in certain rodent and human tumors. We previously demonstrated that tyrosine and phenylalanine restriction suppresses metastatic heterogeneity of B16-BL6 murine melanoma and selects for tumor variants with decreased metastatic potential. In this study, we investigated nm23 expression in the highly metastatic B16-BL6 (ND) melanoma, its nutritionally derived poorly metastatic (LT) variant, and the syngeneic non-tumorigenic Mel-ab melanocytes. No differences in nm23 expression were observed between ND and LT cells, and nm23 expression varied between different isolates. Previously, we showed that metastatic potential of 1-ND cells decreases and is not altered in 1-LT cells after prolonged in vitro cell passage; however, nm23 expression is equivalently increased by 2-fold. In 2-ND and 2-LT cells, expression of nm23 is not different at higher in vitro cell passage. Expression of nm23 decreased about 2-fold when phorbol 12-myristate 13-acetate (PMA) was removed from Mel-ab cells, which induces these cells to become quiescent. Although membrane-associated protein kinase C (PKC) activity decreased after prolonged PMA treatment in all cells, neither nm23 expression nor proliferation of ND and LT cells was affected by PMA. These data indicate that nm23 expression is related to proliferative activity rather than to the suppression of metastatic potential.

Teriparatide (rDNA origin) Injection

MedlinePlus

... teriparatide injection yourself the first time, read the User Manual that comes with it. Ask your doctor or ... injecting the medication how to inject it. The User Manual includes solutions to problems you may have when ...

Financial methods for waterflooding injectate design

DOEpatents

Heneman, Helmuth J.; Brady, Patrick V.

2017-08-08

A method of selecting an injectate for recovering liquid hydrocarbons from a reservoir includes designing a plurality of injectates, calculating a net present value of each injectate, and selecting a candidate injectate based on the net present value. For example, the candidate injectate may be selected to maximize the net present value of a waterflooding operation.

Activation and Protection of Dendritic Cells in the Prostate Cancer Environment

DTIC Science & Technology

2010-10-01

median survival time (in days) ± standard error of the mean (SEM). Skin graft survived for 11.0±0.7 days in control group and 15.8±1.1 days in the...potentiates allogeneic skin graft rejection and induces syngeneic graft rejection. Transplantation. 1998;65:1436-1446. 6. Jemal A, Siegel R, Xu J, Ward E...injections of ETA receptor inhibitor BQ-123 (for 10 days). Skin graft is soft and viable. 22 P.I.: Georgi Guruli; Award # W81XWH-05-1-0181

Talimogene Laherparepvec Injection

MedlinePlus

... sure to replace them right away. You should use rubber or latex gloves when bandaging the injection sites. You should be sure to put all cleaning materials, gloves, and bandages that were used for the injection sites into a sealed plastic bag and throw them away into the garbage.you ...

Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells

PubMed Central

Dong, Lan-Feng; Kovarova, Jaromira; Bajzikova, Martina; Bezawork-Geleta, Ayenachew; Svec, David; Endaya, Berwini; Sachaphibulkij, Karishma; Coelho, Ana R; Sebkova, Natasa; Ruzickova, Anna; Tan, An S; Kluckova, Katarina; Judasova, Kristyna; Zamecnikova, Katerina; Rychtarcikova, Zuzana; Gopalan, Vinod; Andera, Ladislav; Sobol, Margarita; Yan, Bing; Pattnaik, Bijay; Bhatraju, Naveen; Truksa, Jaroslav; Stopka, Pavel; Hozak, Pavel; Lam, Alfred K; Sedlacek, Radislav; Oliveira, Paulo J; Kubista, Mikael; Agrawal, Anurag; Dvorakova-Hortova, Katerina; Rohlena, Jakub; Berridge, Michael V; Neuzil, Jiri

2017-01-01

Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ0 cells) is linked to the acquisition of the host mtDNA. However, the mechanism of mtDNA movement between cells remains unresolved. To determine whether the transfer of mtDNA involves whole mitochondria, we injected B16ρ0 mouse melanoma cells into syngeneic C57BL/6Nsu9-DsRed2 mice that express red fluorescent protein in their mitochondria. We document that mtDNA is acquired by transfer of whole mitochondria from the host animal, leading to normalisation of mitochondrial respiration. Additionally, knockdown of key mitochondrial complex I (NDUFV1) and complex II (SDHC) subunits by shRNA in B16ρ0 cells abolished or significantly retarded their ability to form tumours. Collectively, these results show that intact mitochondria with their mtDNA payload are transferred in the developing tumour, and provide functional evidence for an essential role of oxidative phosphorylation in cancer. DOI: http://dx.doi.org/10.7554/eLife.22187.001 PMID:28195532

Injectable barriers for waste isolation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Persoff, P.; Finsterle, S.; Moridis, G.J.

In this paper the authors report laboratory work and numerical simulation done in support of development and demonstration of injectable barriers formed from either of two fluids: colloidal silica or polysiloxane. Two principal problems addressed here are control of gel time and control of plume emplacement in the vadose zone. Gel time must be controlled so that the viscosity of the barrier fluid remains low long enough to inject the barrier, but increases soon enough to gel the barrier in place. During injection, the viscosity must be low enough to avoid high injection pressures which could uplift or fracture themore » formation. To test the grout gel time in the soil, the injection pressure was monitored as grouts were injected into sandpacks. When grout is injected into the vadose zone, it slumps under the influence of gravity, and redistributes due to capillary forces as it gels. The authors have developed a new module for the reservoir simulator TOUGH2 to model grout injection into the vadose zone, taking into account the increase of liquid viscosity as a function of gel concentration and time. They have also developed a model to calculate soil properties after complete solidification of the grout. The numerical model has been used to design and analyze laboratory experiments and field pilot tests. The authors present the results of computer simulations of grout injection, redistribution, and solidification.« less

Injectable foams for regenerative medicine.

PubMed

Prieto, Edna M; Page, Jonathan M; Harmata, Andrew J; Guelcher, Scott A

2014-01-01

The design of injectable biomaterials has attracted considerable attention in recent years. Many injectable biomaterials, such as hydrogels and calcium phosphate cements (CPCs), have nanoscale pores that limit the rate of cellular migration and proliferation. While introduction of macroporosity has been suggested to increase cellular infiltration and tissue healing, many conventional methods for generating macropores often require harsh processing conditions that preclude their use in injectable foams. In recent years, processes such as porogen leaching, gas foaming, and emulsion-templating have been adapted to generate macroporosity in injectable CPCs, hydrogels, and hydrophobic polymers. While some of the more mature injectable foam technologies have been evaluated in clinical trials, there are challenges remaining to be addressed, such as the biocompatibility and ultimate fate of the sacrificial phase used to generate pores within the foam after it sets in situ. Furthermore, while implantable scaffolds can be washed extensively to remove undesirable impurities, all of the components required to synthesize injectable foams must be injected into the defect. Thus, every compound in the foam must be biocompatible and noncytotoxic at the concentrations utilized. As future research addresses these critical challenges, injectable macroporous foams are anticipated to have an increasingly significant impact on improving patient outcomes for a number of clinical procedures. © 2013 Wiley Periodicals, Inc.

Injectable Foams for Regenerative Medicine

PubMed Central

Prieto, Edna M.; Page, Jonathan M.; Harmata, Andrew J.

2013-01-01

The design of injectable biomaterials has attracted considerable attention in recent years. Many injectable biomaterials, such as hydrogels and calcium phosphate cements, have nanoscale pores that limit the rate of cellular migration and proliferation. While introduction of macroporosity has been suggested to increase cellular infiltration and tissue healing, many conventional methods for generating macropores often require harsh processing conditions that preclude their use in injectable foams. In recent years, processes such as porogen leaching, gas foaming, and emulsion-templating have been adapted to generate macroporosity in injectable calcium phosphate cements, hydrogels, and hydrophobic polymers. While some of the more mature injectable foam technologies have been evaluated in clinical trials, there are challenges remaining to be addressed, such as the biocompatibility and ultimate fate of the sacrificial phase used to generate pores within the foam after it sets in situ. Furthermore, while implantable scaffolds can be washed extensively to remove undesirable impurities, all of the components required to synthesize injectable foams must be injected into the defect. Thus, every compound in the foam must be biocompatible and non-cytotoxic at the concentrations utilized. As future research addresses these critical challenges, injectable macroporous foams are anticipated to have an increasingly significant impact on improving patient outcomes for a number of clinical procedures. PMID:24127230

Discontinuation rates and inter-injection interval for repeated intravesical botulinum toxin type A injections for detrusor overactivity.

PubMed

Veeratterapillay, Rajan; Harding, Chris; Teo, Luke; Vasdev, Nikhil; Abroaf, Ahmed; Dorkin, Trevor J; Pickard, Robert S; Hasan, Tahseen; Thorpe, Andrew C

2014-02-01

To report discontinuation rates, inter-injection interval and complication rates after repeated intravesical botulinum toxin type A for the treatment of detrusor overactivity. Patients with urodyamically proven detrusor overactivity who had two or more botulinum toxin type A injections in the period 2004-2011 at Freeman Hospital, Newcastle Upon Tyne, UK, were considered for the present study. Discontinuation rates, complication rates and interval between botulinum toxin type A treatments were retrospectively analyzed. Overall, 125 patients (median age 53 years, range 19-83 years) were included in the analysis. The female-to-male ratio was 2.4:1 and median follow up was 38 months. A total of 96 patients had idiopathic detrusor overactivity, whereas 29 had neurogenic detrusor overactivity. A total of 667 injections were carried out, with 125 patients receiving two injections, 60 receiving three injections, 28 receiving four injections, 14 receiving five injections, three receiving six injections, three receiving seven injections and two receiving eight injections. The mean interval (±standard deviation) between the first and second injection (n = 125) was 17.6 months (±10.4), between the second and third (n = 60) was 15.7 ± 7.4 months, between the third and fourth (n = 28) was 15.4 ± 8.6 months, and between the fourth and subsequent injections (n = 22) was 11.6 ± 4.5 months. A total of 26% required intermittent catheterization, and 18% developed recurrent urinary tract infections. There was a discontinuation rate of 25% at 60 months. Repeated botulinum toxin type A injections represent a safe and effective method for managing patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity. We have shown that the inter-injection interval remains unchanged up to five injections. © 2013 The Japanese Urological Association.

Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin - assessment by intradermal microdialysis and extraction from the different skin layers.

PubMed

Döge, Nadine; Hönzke, Stefan; Schumacher, Fabian; Balzus, Benjamin; Colombo, Miriam; Hadam, Sabrina; Rancan, Fiorenza; Blume-Peytavi, Ulrike; Schäfer-Korting, Monika; Schindler, Anke; Rühl, Eckart; Skov, Per Stahl; Church, Martin K; Hedtrich, Sarah; Kleuser, Burkhard; Bodmeier, Roland; Vogt, Annika

2016-11-28

Understanding penetration not only in intact, but also in lesional skin with impaired skin barrier function is important, in order to explore the surplus value of nanoparticle-based drug delivery for anti-inflammatory dermatotherapy. Herein, short-term ex vivo cultures of (i) intact human skin, (ii) skin pretreated with tape-strippings and (iii) skin pre-exposed to sodium lauryl sulfate (SLS) were used to assess the penetration of dexamethasone (Dex). Intradermal microdialysis was utilized for up to 24h after drug application as commercial cream, nanocrystals or ethyl cellulose nanocarriers applied at the therapeutic concentration of 0.05%, respectively. In addition, Dex was assessed in culture media and extracts from stratum corneum, epidermis and dermis after 24h, and the results were compared to those in heat-separated split skin from studies in Franz diffusion cells. Providing fast drug release, nanocrystals significantly accelerated the penetration of Dex. In contrast to the application of cream and ethyl cellulose nanocarriers, Dex was already detectable in eluates after 6h when applying nanocrystals on intact skin. Disruption of the skin barrier further accelerated and enhanced the penetration. Encapsulation in ethyl cellulose nanocarriers delayed Dex penetration. Interestingly, for all formulations highly increased concentrations in the dialysate were observed in tape-stripped skin, whereas the extent of enhancement was less in SLS-exposed skin. The results were confirmed in tissue extracts and were in line with the predictions made by in vitro release studies and ex vivo Franz diffusion cell experiments. The use of 45kDa probes further enabled the collection of inflammatory cytokines. However, the estimation of glucocorticoid efficacy by Interleukin (IL)-6 and IL-8 analysis was limited due to the trauma induced by the probe insertion. Ex vivo intradermal microdialysis combined with culture media analysis provides an effective, skin-sparing method for

Enabling skin vaccination using new delivery technologies

PubMed Central

Kim, Yeu-Chun; Prausnitz, Mark R.

2011-01-01

The skin is known to be a highly immunogenic site for vaccination, but few vaccines in clinical use target skin largely because conventional intradermal injection is difficult and unreliable to perform. Now, a number of new or newly adapted delivery technologies have been shown to administer vaccine to the skin either by non-invasive or minimally invasive methods. Non-invasive methods include high-velocity powder and liquid jet injection, as well as diffusion-based patches in combination with skin abrasion, thermal ablation, ultrasound, electroporation, and chemical enhancers. Minimally invasive methods are generally based on small needles, including solid microneedle patches, hollow microneedle injections, and tattoo guns. The introduction of these advanced delivery technologies can make the skin a site for simple, reliable vaccination that increases vaccine immunogenicity and offers logistical advantages to improve the speed and coverage of vaccination. PMID:21799951

Enabling skin vaccination using new delivery technologies

PubMed Central

Kim, Yeu-Chun; Prausnitz, Mark R.

2011-01-01

The skin is known to be a highly immunogenic site for vaccination, but few vaccines in clinical use target skin largely because conventional intradermal injection is difficult and unreliable to perform. Now, a number of new or newly adapted delivery technologies have been shown to administer vaccine to the skin either by non-invasive or minimally invasive methods. Non-invasive methods include high-velocity powder and liquid jet injection, as well as diffusion-based patches in combination with skin abrasion, thermal ablation, ultrasound, electroporation, and chemical enhancers. Minimally invasive methods are generally based on small needles, including solid microneedle patches, hollow microneedle injections and tattoo guns. The introduction of these advanced delivery technologies can make the skin a site for simple, reliable vaccination that increases vaccine immunogenicity and offers logistical advantages to improve the speed and coverage of vaccination. PMID:21472533

Injecting drug use: Gendered risk.

PubMed

Zahnow, Renee; Winstock, Adam R; Maier, Larissa J; Levy, Jay; Ferris, Jason

2018-06-01

Research demonstrates gender related differences in drug-use practices and risk behaviours. Females' structural vulnerability stemming from traditional gender roles and gender-power relations may enhance their propensity to experience injecting related risk. In this paper we explore gender differences in injection practices at the initiation event, during the first year of injecting and in the most recent 12-month period, to inform more effective harm reduction strategies. Data used in this study were drawn from the Global Drug Survey 2015. The study employs chi-square and logistic regression to assess gender differences in injection behaviours in a sample of current injectors residing in six global regions: North-West Europe; Southern Eastern Europe; North America. South America and Oceania. Females were more likely than males to report being injected by an intimate partner at initiation (OR = 4.4, 95%CI: 2.2-8.8), during the first year of injecting (OR = 4.8, 95% CI: 2.4-9.3) and in the most recent 12-month period (OR = 2.5, 95%CI: 1.0-6.2). Females reported greater difficulties accessing sterile equipment (X 2 (2,N = 453) = 8.2, p = 0.02) and were more likely to share injecting equipment than males (X 2 (1,N = 463) = 3.9, p = 0.05). Our findings highlight females' continued dependence on their intimate partner to administer the injection into the first year of their injecting career. Females remained more likely than males to rely on intimate partners for injection during the most recent 12-month period. Females report greater difficulties in sourcing sterile equipment and are more likely to share injecting equipment. We suggest that these findings reflect the broader social structure in which females are disempowered through traditional gender roles and the lack of gender appropriate harm reduction services. Copyright © 2018 Elsevier B.V. All rights reserved.

Accuracy of acromioclavicular joint injections.

PubMed

Wasserman, Bradley R; Pettrone, Sarah; Jazrawi, Laith M; Zuckerman, Joseph D; Rokito, Andrew S

2013-01-01

Injection to the acromioclavicular (AC) joint can be both diagnostic and therapeutic. The purpose of this study was to evaluate the accuracy of in vivo AC joint injections. Case series; Level of evidence, 4. Thirty patients with pain localized to the AC joint were injected with 1 mL of 1% lidocaine and 0.5 mL of radiographic contrast material (Isovue). Radiographs of the AC joint were taken after the injection. Each radiograph was reviewed by a musculoskeletal radiologist and graded as intra-articular, extra-articular, or partially intra-articular. Of the 30 injections performed, 13 (43.3%) were intra-articular, 7 (23.3%) were partially articular, and 10 (33.3%) were extra-articular. When the intra-articular and the partially articular groups were combined, 20 patients (66.7%) had some contrast dye in the AC joint. This study demonstrates that despite the relatively superficial location of the AC joint, the clinical accuracy of AC joint injections remains relatively low.

Predictors of Sharing Injection Equipment by HIV-Seropositive Injection Drug Users

PubMed Central

Latkin, Carl A.; Buchanan, Amy S.; Metsch, Lisa R.; Knight, Kelly; Latka, Mary H.; Mizuno, Yuko; Knowlton, Amy R.

2009-01-01

Among HIV-positive injection drug users (IDUs), we examined baseline predictors of lending needles and syringes, and sharing cookers, cotton, and rinse water in the prior 3 months at follow-up. Participants were enrolled in INSPIRE, a secondary prevention intervention for sexually active HIV-positive IDUs in four US cities during 2001–2005. The analyses involved 357 participants who reported injecting drugs in the prior six months at either the 6- or 12-months follow-up visit. About half (49%) reported at least one sharing episode. In adjusted analyses, peer norms supporting safer injection practices, and having primary HIV medical care visits in the prior 6 months were associated with reporting no sharing of injection equipment. Higher levels of psychological distress was associated with a greater likelihood of reporting drug paraphernalia sharing. These findings suggest that intervention approaches for reducing HIV-seropositive IDUs’ transmission of blood-borne infections should include peer-focused interventions to alter norms of drug paraphernalia sharing and promoting primary HIV care and mental health services. PMID:19186356

Predictors of sharing injection equipment by HIV-seropositive injection drug users.

PubMed

Latkin, Carl A; Buchanan, Amy S; Metsch, Lisa R; Knight, Kelly; Latka, Mary H; Mizuno, Yuko; Knowlton, Amy R

2008-12-01

Among HIV-positive injection drug users (IDUs), we examined baseline predictors of lending needles and syringes and sharing cookers, cotton, and rinse water in the prior 3 months at follow-up. Participants were enrolled in Intervention for Seropositive Injectors-Research and Evaluation, a secondary prevention intervention for sexually active HIV-positive IDUs in 4 US cities during 2001-2005. The analyses involved 357 participants who reported injecting drugs in the prior 6 months at either the 6- or 12-month follow-up visit. About half (49%) reported at least 1 sharing episode. In adjusted analyses, peer norms supporting safer injection practices and having primary HIV medical care visits in the prior 6 months were associated with reporting no sharing of injection equipment. Higher levels of psychological distress were associated with a greater likelihood of reporting drug paraphernalia sharing. These findings suggest that intervention approaches for reducing HIV-seropositive IDUs' transmission of blood-borne infections should include peer-focused interventions to alter norms of drug paraphernalia sharing and promoting primary HIV care and mental health services.

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 ...

Prevalence and risk factors for injection site skin infections among people who inject drugs (PWID) in Tehran.

PubMed

Noroozi, Mehdi; Armoon, Bahram; Ghisvand, Hesam; Noroozi, Alireza; Karimy, Mahmood; Bazrafshan, Mohammad Rafi; Marshall, Brandon D L; Dieji, Bahman

2018-05-20

Injection drug use is one of the major public health problems in Iran. Injection drug use is associated with numerous negative health outcomes, such as blood-borne infections (HIV, HCV) and injection site skin infections (abscesses, cellulitis). The aim of this study was to determine prevalence of injection site skin infections and its associated risk factors among people who inject drugs (PWID) in Tehran, Iran. The cross-sectional study was conducted from March to August 2016 in Tehran province. A total of 500 PWID were recruited by convenience and snowball sampling from Drop-in Centers (DIC) in the South of Tehran. Our primary outcomes were self-report of ever having injection sites skin infections and receiving treatment for them. We first examined associations between individual variables and lifetime history of having injection site infections in bivariate analysis using the chi-square or Fisher's exact tests, as appropriate. Variables with P-value <.2 were included in a multiple logistic regression model. Overall, 40% (CI95%: 30.3%, 52.2%) of participants reported ever having an injection site infection. In the multivariable model, those with low socioeconomic status (AOR = 2.4, P = .03), self-reported as HIV positive (AOR =1.6, P = .01), reporting more than 3 injections per day (AOR = 4.1, P = .03) and reuse of their own syringes (AOR = 8.5, P = .03) were more likely to have injection sites skin infections. PWID who used needle and syringe program (NSP) services were less likely to report injection site infections (AOR = 0.5, P = .04). We have identified several risk factors for injection sites infections among PWID, including frequency of injection per day, reuse of their own syringes, not using NSP services, HIV status, socioeconomic status with skin infections in PWID. Prevention strategies to reduce skin infections should focus on high-risk injection behaviors and improving access to NSP services. © 2018 Wiley Periodicals, Inc.

Computerized Dental Injection Fear Treatment