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PubMed1982

Pathways to inflammation induced by immune complexes: development of the Arthus reaction.

The changes associated with inflammation induced by immune complexes (reversed passive Arthus reaction induced with egg albumin-anti-egg albumin) were quantitated and the kinetics of the various vascular phenomena were ascertained. Hyperemia, increase in vascular permeability, platelet accumulation, and polymorphonuclear (PMN) leukocyte accumulation occurred relatively early after induction of the inflammatory lesions, and peaked in 2-4 h. Hemorrhage peaked in 6-h-old lesions. Morphological studies confirmed that almost all infiltrating cells were PMN leukocytes and immunofluorescent tracer studies showed immune complexes in vessel walls as early as 15 min after i.v. injection of the fluoresceinated antigen and the intradermal injection of antibody. By 8 h the progression of the lesions had subsided and by 24 h there were signs of resolution. A pathway for the development of the inflammatory lesions induced with immune complexes is proposed.

Animals↗
PubMed1998

Type-1 hypersensitivity reactions to Malassezia pachydermatis extracts in atopic dogs.

OBJECTIVE: To investigate the potential allergenic role of the yeast Malassezia pachydermatis in dogs with clinical diagnosis of atopic dermatitis. ANIMALS: 5 clinically normal nonatopic dogs, 10 atopic dogs with cytologic evidence of Malassezia dermatitis, and 12 atopic dogs without cytologic evidence of Malassezia dermatitis. PROCEDURE: A crude yeast extract was produced by disrupting the cell wall of M pachydermatis. The crude extract and 8 of its fractions, which were generated by fractionation in a high-performance liquid chromatography column, were injected along with 46 commercial allergens for intradermal allergy testing of normal and atopic sample populations. Significant difference between atopic populations was evaluated, using a threshold concentration of crude yeast extract that failed to induce wheal-and-flare responses in normal nonatopic dogs. RESULTS: Atopic dogs with cytologic evidence of Malassezia dermatitis had significantly greater wheal-and-flare reactions to intradermal injection of crude extract of M pachydermatis than did atopic dogs without cytologic evidence of Malassezia dermatitis. CONCLUSIONS: It is concluded that M pachydermatis is capable of promoting type-1 hypersensitivity reactions in dogs with an atopic dermatitis phenotype. CLINICAL RELEVANCE: Currently, Malassezia dermatitis is principally managed by use of antifungal chemotherapy. Because the yeast appears to be a contributing allergen in dogs with atopic dermatitis, hyposensitization with M pachydermatis extracts may offer a future alternative to extended or repeated episodic administration of antifungals for extended control of recurrent infections.

Allergens↗
PubMed1997

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

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

Animals↗
PubMedDate not supplied

Injection of vitamin A acid, vitamin E, and vitamin C for treatment of tissue necrosis.

Experimental studies concerning All-Trans Retinoic acid 0.1% with the antioxidant action of the Vitamin E (tocopherol acetate 0.20%) and Vitamin C (coated ascorbic acid 0.20%) efficacy in both the vascular neoformation induction and cellular membrane stabilization have been conducted by us to improve skin necrosis regression after routine plastic surgeries. Patients after rhytidectomy, breast reduction, and abdominoplasty with localized skin flap necrosis, were submitted to daily intradermic injections for a period of 15 days and had their skin healed by the effects of these vitamins.

Adolescent↗
PubMedDate not supplied

Reducing the discomfort of lidocaine administration through pH buffering.

PURPOSE: A prospective, double-blind study was undertaken to evaluate the effect of using a buffered lidocaine solution on the perception of pain experienced by a patient during its intradermal injection. PATIENTS AND METHODS: One hundred fifty patients undergoing diagnostic angiographic and interventional procedures at the authors' institution were randomly assigned to receive a 1-mL aliquot of one of three lidocaine solutions: plain 1% lidocaine, 1% lidocaine diluted with normal saline in a 10:1 ratio, and 1% lidocaine diluted with 8.4% sodium bicarbonate in a 10:1 ratio. The lidocaine solutions were administered intradermally over 10-15 seconds. A numerical value was placed on the patient's perception of pain, separate from that associated with the 25-gauge needle insertion, with use of a linear visual analog scale. RESULTS: Mean pain scores were as follows: for the 1% lidocaine solution, 2.83 +/- 2.60; for 1% lidocaine plus normal saline solution, 2.89 +/- 2.34; and for 1% lidocaine plus sodium bicarbonate solution, 1.37 +/- 1.73 (P = .0018). CONCLUSION: Buffering lidocaine significantly decreased the discomfort associated with its administration as a local anesthetic.

Adolescent↗
PubMed1981

Studies on pruritogenic and histamine-releasing effects of some putative peptide neurotransmitters.

Pruritus, whealing and axon-reflex erythema appeared in human skin after intradermal injection of (i) several peptides with a putative transmitter function, i.e. vasoactive intestinal polypeptide (VIP) (10(-7)--10(-4) M), [Gln4]-neurotensin (10(-7)--10(-4) M), neurotensin (10(-5)--10(-4) M) and secretin (10(-5)--10(-4) M), which were compared with substance P (10(-7)--10(-5) M) previously shown to be one of the most potent histamine liberators when administered intradermally in humans; (ii) the basic polypeptide protamine (10(-7)--10(-4) M); and (iii) histamine (0.3-10 micrograms/ml) and the histamine liberator compound 48/80 (0.3-10 micrograms/ml). The reactions were inhibited in a dose-related manner by the antihistamine mepyramine, indicating that the peptide-induced responses were mediated by released histamine. This was further confirmed by the histamine release observed when the peptides were incubated with rat peritoneal mast cells. In human skin, VIP was more potent than the other neuropeptides and had roughly the same potency as substance P. The two adjacent basic amino-acid residues and the amide substitution of the terminal C-group of VIP, in addition to its strong net basic charge, may explain its potency as a histamine releaser.

Adolescent↗
PubMed2000

Cutaneous injection of human subjects with macrophage inflammatory protein-1 alpha induces significant recruitment of neutrophils and monocytes.

Macrophage inflammatory protein (MIP-1 alpha), a member of the CC chemokine subfamily, has been shown to attract T cells and monocytes in vitro and to be expressed at sites of inflammation. Although the in vitro activities of MIP-1 alpha have been well documented, the in vivo biological activities of MIP-1 alpha in humans have not been studied. To address this, we challenged human subjects by intradermal injection with up to 1000 pmol of MIP-1 alpha and performed biopsies 2, 10, and 24 h later. Although no acute cutaneous or systemic reactions were noted, endothelial cell activation, as indicated by the expression of E-selectin, was observed. In agreement with its in vitro activity, monocyte, lymphocyte, and, to a lesser degree, eosinophil infiltration was observed, peaking at 10-24 h. Surprisingly, in contrast to its reported lack of in vitro neutrophil-stimulating activity, a rapid infiltration of neutrophils was observed in vivo. This neutrophil infiltration occurred as early as 2 h, preceding the appearance of other cells, and peaked at 10 h. Interestingly, we found that neutrophils in whole blood, but not after isolation, expressed CCR1 on their cell surface. This CCR1 was thought to be functional as assessed by neutrophil CD11b up-regulation following whole-blood MIP-1 alpha stimulation. These studies substantiate the biological effects of MIP-1 alpha on monocytes and lymphocytes and uncover the previously unrecognized activity of MIP-1 alpha to induce neutrophil infiltration and endothelial cell activation, underscoring the need to evaluate chemokines in vivo in humans.

Adolescent↗
PubMed1987

Prospects for a nonliving vaccine against schistosomiasis based on cell-mediated immune resistance mechanisms.

We have designed a vaccine model based on induction of cell-mediated immunity and shown that it protects mice against Schistosoma mansoni infection. Mice are immunized by intradermal injection with schistosome antigens plus BCG. Resistance is dependent on the route of antigen presentation and the adjuvant chosen. The pattern of resistance correlates with sensitization of T lymphocytes for production of gamma interferon, a macrophage activating lymphokine that stimulates the cellular effector mechanism of protection. Purified schistosome paramyosin, a muscle cell component present in soluble parasite antigenic preparations, is immunogenic for T lymphocytes and induces resistance when given intradermally with BCG. It is likely that this protein, and possibly other soluble molecules that are released by the parasites of a challenge infection, induce a cellular inflammatory response resulting in larval trapping and/or killing by activated macrophages. These results verify the feasibility of a vaccine against schistosomiasis based on induction of cell-mediated immune resistance mechanisms.

Adjuvants, Immunologic↗
PubMed1994

Screening of depigmenting compounds for the development of an alternate method of branding beef cattle.

The impetus to find alternative methods to stressful routine management procedures has increased in recent years in the hope of improving animal welfare. The potential of using depigmenting compounds to create a permanent visible mark was evaluated in two beef heifers. Eight compounds (hydroquinone [H], 4-ethoxyphenol [4-EP], 4-methylcatechol [4-MC], 4-tert-butylcatechol [4-t-BC], 4-methoxyphenol [4-MP], monobenzone [M], hydroquinone bis (2-hydroxyethyl) ether (HHEE), and catechol [C]) were injected intradermally at concentrations of 10 and 20%. These compounds were screened in four different carriers (ethanol, glycerol, propylene glycol, and liposome cream) to test their effectiveness in producing depigmented hair. Transdermal patches containing 5, 7, and 10% liposome preparations of 4-MC and 4-MP produced depigmentation, but this depigmentation was not as visible as when the same preparations were injected. Histological examination of biopsies and observations of the injected sites were compared to sites that were only injected with the carrier solution. Compounds H, 4-EP, 4-MC, 4-t-BC, 4-MP, and M produced visible depigmentation lasting up to 3 mo. The duration of the effect seemed dependent on the hair cycle length and stage of cycle at time of application. None of the depigmenting compounds tested produced a permanent depigmenting effect.

Administration, Cutaneous↗
PubMed1991

Cutaneous ulceration due to contrast extravasation. Experimental assessment of injury and potential antidotes.

Severe cutaneous ulceration may occur as a result of contrast media extravasation. We established a definitive animal model for assessing the cutaneous toxicity of commonly employed agents and used this model to evaluate possible antidotes to the effects of contrast media extravasation. The contrast agents studied were: meglumine/sodium diatrizoate 76%, meglumine iothalamate 60% and 43%, meglumine/sodium ioxaglate 60%, iohexol 350, and iopamidol 370, in varying volumes and osmolalities. Hypertonic saline (950 and 1900 mOsm/kg) also was injected. Agents were injected intradermally into BALB/c mice. The higher osmolality agents produced dose-dependent skin ulcerations. The lower osmolality agents failed to produce any skin lesions after the same volume doses. Hypertonic saline produced skin toxicity in a dose-dependent fashion similar to hyperosmolar contrast agents. Three antidotes were tested: hyaluronidase, topical heat, and topical cold. Hyaluronidase significantly reduced skin toxicity when injected immediately following contrast injection. Cold also significantly reduced skin toxicity, while heat caused no improvement.

Animals↗
PubMed2006

ACP gel: a new hyaluronic acid-based injectable for facial rejuvenation. Preclinical data in a rabbit model.

BACKGROUND: Facial aging results from reduced biosynthetic activity of dermal fibroblasts and decreased deposition of extracellular matrix components, such as hyaluronic acid, a glycosaminoglycan responsible for skin hydration and turgidity. Exogenous hyaluronic acid injections provide a safe though short-term solution for facial rejuvenation. Using a rabbit model, the authors investigated residence time and tolerability of ACP gel, a new hyaluronic acid cross-linked derivative, compared with high-molecular-weight native hyaluronic acid currently used for facial rejuvenation (Ial System). METHODS: ACP gel 1% and 2%, Ial System, and saline were intradermally injected into the backs of 12 New Zealand rabbits: six animals were used to follow volume maintenance and redness up to 10 days and the other six animals were euthanized at days 2, 6, 8, 10, 14, and 21 (one animal per time point) to histologically assess biocompatibility. RESULTS: ACP gel 2% had the longest residence time, showing a significantly better volume maintenance than the other samples, especially in the initial study period (71 percent of original volume versus 23 percent and 21 percent of ACP gel 1% and Ial System, respectively, at day 2). Macroscopically, no adverse events were observed in the treated animals. Histologic examination confirmed the absence of adverse events, persistent inflammation, tissue degeneration, or necrosis. ACP gel macrophage-mediated phagocytosis was more persistent with respect to the Ial System, consistent with its longer residence time. CONCLUSION: ACP gel 2% is a promising dermal biorevitalizer, characterized by a high safety profile and prolonged residence time in relation to native high-molecular-weight hyaluronic acid.

Animals↗
PubMed1990

Inhibition of anti-IgE induced skin response in normals by formoterol, a new beta 2-adrenoceptor agonist, and terbutaline. 1. Dose response relation and duration of effect on the early wheal and flare response.

The intention of the present study was to compare formoterol and terbutaline regarding ability to inhibit immediate wheal and flare responses (WFR) to anti-human IgE with focus on the duration of anti-WFR action. Formoterol is a novel beta 2-adrenergic agonist with a prolonged duration of bronchodilation capacity after inhalation. The drugs injected intradermally 2 min prior to challenge with anti-IgE in volunteers produced a dose-dependent inhibition of the WFR in the range 1pg-100ng (formoterol) and 1ng-1 microgram (terbutaline). Formoterol was 70 times (flare) and 25 times (wheal) more potent (ID40) than terbutaline on a weight basis. The duration of the anti-WFR action for formoterol, injected in a 25 times lower dose than terbutaline, was significantly longer, namely greater than 24 h versus 8 h for terbutaline. The histamine-induced wheal reaction was attenuated by 15% and 25% by terbutaline and formoterol, respectively. The results indicate a higher beta 2-receptor activity for formoterol with respect to inhibition of IgE-dependent mast cell mediator release in addition to an anti-leak effect exerted by both drugs. The prolonged duration of antagonistic effect by formoterol on the WFR to anti-IgE might be due to the lipophilic property of the drug, with an expected higher retention of formoterol at the target tissue compared with the more hydrophilic compound terbutaline.

Adrenergic beta-Agonists↗
PubMed1996

Similar effectiveness of Fab and F(ab')2 antivenoms in the neutralization of hemorrhagic activity of Vipera berus snake venom in mice.

The ability of two antivenoms to Vipera spp., consisting of Fab (Therapeutic Antibodies), or of F(ab')2 (Zagreb Institute of Immunology) antibody fragments, to neutralize the hemorrhagic activity of Vipera berus snake venom in mice, was compared. First, the neutralizing potency was determined by in vitro preincubation of venom and antivenom, followed by intradermal injection into mice and subsequent measurement of the hemorrhagic area. Both antivenoms had the same anti-hemorrhagic potency, in terms of volume of antivenom/mass of venom, with an estimated ED50 (50% reduction of the effect) of 80 microliters antivenom/mg venom. Therefore, no adjustments in dose were necessary for subsequent in vivo comparative experiments. When the antivenoms were administered intravenously into mice immediately after intradermal venom injection, there was no difference in their effectiveness in reducing hemorrhagic lesions, at all doses tested. These results indicate that neutralization of local hemorrhagic activity of V. berus venom in vivo is not improved by the use of the smaller Fab fragments, in comparison to F(ab')2, when equivalent neutralizing units are injected. However, this does not exclude the possibility that other clinically relevant venom effects may be neutralized with different efficiency by Fab or F(ab')2 fragments of antibodies.

Animals↗
PubMed1967

Persistence of group a streptococcal cell walls related to chronic inflammation of rabbit dermal connective tissue.

Antibodies specific for the mucopeptide and group-specific C polysaccharide antigens of Group A streptococcal cell walls were prepared by acid dissociation of immune precipitates, and labeled with either fluorescein or (125)I. Employing both fluorescent and radioautographic procedures the persistence of the antigens was followed in skin sites injected with cell wall fragments. Both antigens persisted within macrophages for at least 54 days in those animals which developed no chronic tissue response. In animals which did develop chronic nodular lesions the concentration of antigen decreased as the inflammatory process subsided. Lesion activity was thus associated with the presence of cell wall material. The fate of these antigens was also determined following the intradermal injection of intact Group A streptococcal cells. Cell wall antigens persisted in the tissue site considerably longer than morphologically identifiable streptococci, indicating that cell wall fragments are released during dismantling of streptococci in phagocytic cells.

Animals↗
PubMed1983

Attenuation of dermal toxicity of doxorubicin by liposome encapsulation.

The severe tissue damage which occurs when doxorubicin (Dxn) is extravasated during infusion has been attenuated by encapsulating the drug in anionic liposomes. Mice were injected intradermally with either 0.05 or 0.10 mg of Dxn in the free or liposome-entrapped form. At both dose levels, the animals receiving free drug developed dermal lesions at a higher frequency and of a greater severity than did those animals receiving Dxn-liposomes. Determination of tissue-associated fluorescence indicated that free Dxn was removed from the area of the dermal injection more rapidly than was the liposome-entrapped drug. The data suggest that the dermal toxicity of Dxn may be determined more by its mode of disposition than by the absolute amount of drug in tissue. Similar observation was made earlier for the Dxn-induced chronic cardiotoxicity.

Animals↗
PubMed2005

Fluorescence fibre-optic confocal microscopy of skin in vivo: microscope and fluorophores.

BACKGROUND/AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Dermoscopy↗
PubMed2005

Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice.

The pruritogenic potency of tryptase and its involvement in anti-pruritic effect of intravenous nafamostat mesilate (NFM) were studied in mice. An intradermal injection of tryptase (0.05-1 ng/site) elicited scratching in ICR mice, while chymase was without effects at doses of 0.05-50 ng/site. The dose-response curve of tryptase action was bell-shaped and the effect peaked at 0.1 ng/site (approximately 0.7 fmol/site). NFM (10 mg/kg) inhibited scratching induced by tryptase but not by histamine and serotonin. NFM (1-10 mg/kg) produced the dose-dependent inhibition of scratching induced by intradermal compound 48/80 (10 microg/site). The inhibition by NFM (10 mg/kg) was abolished in mast cell-deficient (WBB6F1 W/W(V)) mice, but not in wild-type (WBB6F1 +/+) mice. NFM (10 mg/kg) suppressed tryptase activity in the mouse skin. Proteinase-activated receptor-2 (PAR-2) neutralizing antibody (0.1 and 1 microg/site) and the PAR-2 antagonist FSLLRY (10 and 100 microg/site) inhibited scratching induced by tryptase (0.1 ng/site) and compound 48/80 (10 microg/site). These results suggest that mast cell tryptase elicits itch through PAR-2 receptor and that NFM inhibits itch-associated responses mainly through the inhibition of mast cell tryptase.

Animals↗
PubMed1975

Physiopathological aspect of Glynn's type of experimental arthritis.

Knee joint arthritis is induced among rabbits previously immunized by intradermal injection with egg albumin (EA) emulsified in adjuvant containing either M. tuberculosis or M. butyricum, then by intra-articular injection with EA. Arthritis evolution involves two phases, an early one during the first 2 months and a late one from 3 months to 1 year. During the early phase, arthritis intensities are similar no matter which Mycobacterium is used. However, during the late phase, only rabbits immunized with M. tuberculosis develop self-perpetuating arthritis. Among more than 50% of arthritic rabbits, immunological lesions of aortic artery and cardiac valvules are found. Among the rabbits immunized with M. tuberculosis, the humoral anti-EA antibody level remains constant during the whole arthritis evolution; but, among the rabbits immunized with M. butyricum, the arthritis intensity decreases from 3 months of evolution. The correlation between arthritis index (AI) and humoral antibody level is only significant among the rabbits with early arthritis. The intradermally immunized rabbits show a positive skin test with EA and tuberculin. The more intense the cutaneous reactions, the greater the chances of developing self-perpetuating arthritis after the EA intra-articular injection. The fluorescent anit-EA antibodies in the synovia and spleen are found only among the early arthritis. After 2 months of evolution, fluorescent antibodies disappear whatever the immunization may be. Among the immunized rabbits, it is probable that antigenic EA does not persist in the synovia. Indeed, the autologous inflamed synovia transplantation, from the donor-challenged knee joint, does not develop an inflammatory reaction in the non-challenged knee joint. The fluorescent immunoglobulins IgG and IgM in the synovium of arthritic rabbits are found with the same percentages as fluorescent anti-EA antibodies. The lymphocyte response to EA, PHA and PWM are positive whatever the immunization and arthritis evolution may be. There is no correlation between AIs and lymphocyte responses to specific and nonspecific mitogens. It is probable that self-perpetuation depends closely on M. tuberculosis whose adjuvant power is much superior than M. butyricum and not on antigenic EA whose essential role would be to trigger the inflammatory process.

Animals↗